The Keller Laboratory at OHSU

Scientific Writer needed

2012-02-08T14:59:00.000-08:00

We are looking for a volunteer technical writer from the community to co-author a scientific paper on childhood cancer research from results already compiled. This endeavor is an experiments of sorts to see whether we can begin to blend the community with academics to create a seamless and efficient way of moving towards new treatments for childhood cancers. If you have time and interest, please contact Charles at keller (at) ohsu.edu. with thanks, the Keller Lab team.

Our thanks to the Ethan Jostad Foundation

2012-01-29T23:47:00.001-08:00

We are grateful to partner with the Ethan Jostad Foundation for Childhood Cancer in the search for treatments of alveolar rhabdomyosarcoma. This foundation has both patient/family assistance and research as the center of their mission. We are thankful for the gift of $11,400 that supports the preclinical studies of a specific new agent potentially capable of stopping tumor cell spreading (metastasis). These studies will specifically employ our genetically-engineered mouse model of alveolar rhabdomyosarcoma. We are honored to be part of Ethan's rememberance.

[ pictured: Guangheng Li and Charles Keller (left) with Chris and Kim Jostad (right) ]

Graphics Volunteer Needed

2012-01-24T11:42:00.001-08:00

We are hoping to work with a volunteer in the community with graphic arts/communication experience. The project is about 6 weeks long and may take 8-12 hours a week. If you have time and interest, please contact Charles at keller (at) ohsu.edu. with thanks, the Keller Lab team

Congratulations, Ken and Anu!

2012-01-17T13:32:00.001-08:00

Congratulations to authors Ken and Anu whose manuscript describing the role of Protein Kinase C iota in rhabdomyosarcoma was accepted today to the journal, Oncogene. Co-authors include lab alumni Laura and Sheila, UTHSCSA biostatistics collaborators Joel Michalek and Lee Ann Zarzabal, Mayo PKC biology collaborators Capella Weems and Alan Fields, and long-time sarcoma pathologist collaborator Brian Rubin at Cleveland Clinic. This work was supported by by NIH/NCI grant 1R01CA133229-04 and -05 awarded to the Keller lab and NIH/NCI grant 4R01CA081436-13 and the V Foundation for Cancer Research awarded to Dr. Fields.

For a full list of KellerLab & collaborator publications in the last year and beyond, see http://www.ncbi.nlm.nih.gov/sites/myncbi/collections/public/10calZ-r8sAIil6mkZzynGqAV/?sort=date&direction=descending .

Congratulations, Anu!

2012-01-13T07:41:00.000-08:00

(01/13/12): Article entitled, "(18) F-FDG microPET imaging detects early transient response to an IGF1R inhibitor in genetically engineered rhabdomyosarcoma models" is now online here as PMID 22238194.

(12/17/11) Many congratulations to lab alumni, Anu, on her study from our lab of PET scan monitoring of targeted therapy responses in alveolar & embryonal rhabdomyosarcoma, which has been accepted for publication in Pediatric Blood & Cancer. Co-authors include current lab member Jinu, lab alumni Laura & Suresh, and collaborators Lee Ann Zarzabel & Joel Michalek (UTHSCSA), Stan McHardy (SWRI), Doug Hawkins (Seattle Children's Hospital) and Suman Malempati (OHSU Doernbecher Children's Hospital).

JMCCF funds Rhabdomyosarcoma Research

2011-12-29T09:52:00.000-08:00

We are grateful to the Joanna McAfee Childhood Cancer Foundation for our new 2012 research grant of $12,000 for the project, "60 by 60: Finding the Very Best Targeted Therapy Combination for Alveolar Rhabdomyosarcoma". JMCCF is a very important organization not only for funding research, but also for supporting families of childhood cancer patients in central Georgia and beyond.

We are thankful to our long term partners at JMCCF for allowing us to be part of their mission.

Welcoming Amy!

2011-12-29T00:58:00.000-08:00

We are pleased to Amy Paul join our laboratory as a new intern in pediatric oncology translational research. Amy is a recent graduate of the OHSU School of Nursing and will be functioning in important roles for our childhood tumor bank & registry as well as a canine personalized sarcoma therapy trial.

in her own words:

"My interest in working in pediatric oncology first arose in 2008 when I spent my first summer during nursing school as a volunteer camp counselor at a camp for children with cancer. For 8 days, I bonded with 18 middle-school aged girls all affected by cancer in some way either as a patient, survivor or as a sibling, I then realized that this was my hearts calling in life as a Registered Nurse and community advocate for cancer. I then started training for a marathon with a local chapter of Team in Training for Leukemia and Lymphoma Society where I recognized and learned the growing importance for cancer research, which deepened my hearts desire to expand my participation in this field of medicine. The ability to directly work with the children and families at Doernbecher's (Children's Hospital) as well in the research lab is an incredible opportunity that will only add to my knowledge and experience in my future nursing practice as I aspire to be a pediatric oncology nurse."

We're excited for Amy to be part of our team and look forward to furthering her career!

Sincere thanks to ABC2 and CureSearch !

2011-12-24T14:29:00.000-08:00

In an incerdible development, ABC2 and CureSearch for Children's Cancer have jointly funded a supplement to the our international collaboration entitled, "Rapid Preclinical Development of a Targeted Therapy Combination for DIPG". The two new sponsor partners provide $76,000 and $25,000, respectively, for a total of $101,000. Their new supplement will allow us to exon sequencing of all 16 cell lines, their primary tumor and paired normal DNA via the laboratory of Dr. Paul Spellman (OHSU; see his recent functional genomics paper here). From this data we will prioritize combination drug testing on the most clinically ‘representative’ samples (i.e., samples that have classical DIPG findings which are in order: c‐MET amplification, p53 deletion, PDGFRA amplification, IGF1R/IGF2 amplification, CDK4/CDK6 gain or Shh pathway mutation, EGFR amplification or KRAS/NRAS mutation) or cell lines that are most similar overall to one another (i.e., not outliers).

This project is more fully described here and here. This study was originally made possible by a $100,000 grant from TheCureStartsNow. An additional $28,000 supplement from The Lyla Nsouli Foundation for Children’s Brain Cancer Research further allowed our project to expand to the 2 participating European collaborators. The new $101,000 from ABC2 and CureSearch for Children's Cancer adds significant new scope to this endeavor. The interesting aspect is that a large part of the new scope was envisioned by our ABC2 partner's scientific advisory board - an example of the value of scientific and strategic partnership.

Personalized Cancer Therapy for Pediatric Brain Tumors?

2011-12-10T19:15:00.000-08:00

Congratulations to Lara for her very thoughtful editorial on this topic, which is now available online. Don't miss the accompanying Supplemental Table of potentially-actionable biomarkers.

now in print: EGFR as a Therapeutic Target in Alveolar Rhabdomyosarcoma

2011-12-06T06:13:00.000-08:00

[ first posted 2/11/2011 and now updated]

The report of our Pediatric Preclinical Testing Initiative at OHSU on EGFR as a therapeutic target in the childhood muscle cancer rhabdomyosarcoma has been accepted for publication in the journal, Sarcoma. Co-authors include Keller Lab alumni Sheila Hampton, Courtney Kubicek, Laura Nelon, Aoife Kilcoyne; statistician collaborators Lee Ann Zarzabal and Joel Michalek; experimental therapeutics collaborator Frank Giles; and pathologist collaborator, Brian Rubin. This work was funded by the Rally Foundation in honor of Matthew Butterfield. Trainee Jinu Abraham is also a past Scott Carter Foundation fellow.

[ update 5/11/2011: the paper can now be viewed online here. ]
[ update 12/06/2011: the paper is now in print here. ]

now in print: Bortezomib acts through NOXA in Medulloblastoma

2011-12-05T19:40:00.000-08:00

Congratulations again to lab alumni Sachiko and Monika for the publication this month in the Journal of Neuro-Oncology of our study, "Bortezomib stabilizes NOXA and triggers ROS-associated apoptosis in medulloblastoma". Co-authors include lab alumni Tohru and Laura. This was a very exciting study funded by the National Brain Tumor Society and the Hyundai Motor Corporation Hope on Wheels Program (precursor studies were funded by St Baldrick's Foundation). These results have piqued our interest in similar compounds such as Carfilzomib for pediatric medulloblastoma.

Congratulations, Monika & Sachiko!

2011-12-03T15:15:00.001-08:00

Congratulations to lab alumni Sachiko,Monika, Suresh, Laura, Aofe and current lab members Jinu & Sangeet, as well as collaborators Marti Hanes, Frank Giles and Brian Rubin on our study entitled, "Preclinical Testing of Tandutinib in a Transgenic Medulloblastoma Mouse Model" that is now published online in the Journal of Pediatric Hematology & Oncology. This work was supported by the Rally Foundation in memory of Coleman Larson.

Multi-disciplinary Collaboration

2011-12-01T15:23:00.000-08:00

Many thanks to our Boston-area collaborators for partnership in studying biology and new therapeutics for rhabdomyosarcoma. So much comes from working across disciplines.

Congratulations, Sangeet!

2011-11-28T20:48:00.001-08:00

We are excited that Sangeet's pilot project proposal, " Chemokine Regulation of the Leptomeningeal Metastasis of Medulloblastoma " has been funded by the Knight Cancer Institute Translational Research Group and made possible by the Schnitzer Investment Corp.

way to go, Sangeet!

To Friends at the Schnitzer Investment Corp, our team and I are grateful that you have made possible our pilot grant. Preventing the spread of brain tumor cells to the spine is an important issue for children of Oregon and across the world. We hope to take the opportunity you have created for us to study this cancer-related process to not only understand how it occurs, but also to understand how to prevent it (or to treat it if already established). As you have proven, the community is always an important part of new and innovative research endeavors. Charles

Lyla Nsouli Foundation funds Supplement to the DIPG Consortium

2011-11-28T12:28:00.002-08:00

We are grateful to the The Lyla Nsouli Foundation for Children’s Brain Cancer Research for the $28,000 supplement to our TheCureStartsNow funded project entitled, "Rapid Preclinical Development of a Targeted Therapy Combination for DIPG". This supplement allows us to expand our six institution consortium in North America to include 2 other expert laboratories in Europe:

Dannis G. van Vuurden MD, MSc, & Esther Hulleman, VU Cancer Center Amsterdam, and
Jacques Grill, Institut Gustave-Roussy, Villejuif, France

The ultimate goal is to move the most effective single agent or combination therapy forward to early phase clinical trials in the next 18-24 months. This is the first time that a group of basic and translational scientists and physicians from eight institutions throughout North America and Europe have come together as a consortium to focus on DIPGs and to focus on a bench-to-bedside approach to rationally target therapy for children with DIPGs.

For the Open Science Forum week to week update of this project, click here.

TheCureStartsNow funds DIPG International Preclinical Study

2011-11-20T21:14:00.002-08:00

We and our collaborators are grateful for the new $100,000 award from The Cure Starts Now circle of foundations for our project, Rapid Preclinical Development of a Targeted Therapy Combination for DIPG. We are excited to get this project underway immediately, which addresses the goal our multi-national team and this foundation and its supporters share in making DIPG a uniformly survivable cancer. Our team consists of the following laboratories:

Charles Keller MD, Kellie Nazemi MD, Nate Selden MD, PhD and Dan Guillaume MD, PhD at the Oregon Health & Science University

Oren Becher MD, Duke University Medical Center

Michelle Monje MD, PhD, Stanford University

Maryam Fouladi MD, Cincinnati Children’s Hospital Medical Center

Cynthia Hawkins, MD, PhD, University of Toronto

Xiao-Nan Li MD, PhD, Baylor College of Medicine

We are again thankful to The DIPG Symposium Collaboration, The Cure Starts Now Foundation, Reflections of Grace Foundation, The Jeffrey Thomas Hayden Foundation, Cancerfree Kids, Carly’s Crusaders, The Max Lacewell Foundation, Smiles for Sophie Forever Foundation and Benny’s World Foundation for making our project possible.

For the Open Science Forum week to week update of this project, click here.

Our thanks to the Kyla McCullough Gift Fund

2011-11-03T23:22:00.000-07:00

We sincerely thank the family and community that remember Kyla McCullough through the KMGF. For the second year in a row, the KMGF has sponsored a scientific instrument purchase - here an Intravital Microscope to facilitate improved studies of leptomeningeal metastasis. We are grateful for this generous gift, and the chance to be part of Kyla's rememberance.

CTOS - Second International Conference on Sarcoma Biology

2011-10-27T15:48:00.000-07:00

It has been a productive set of tandem meetings. Charles presented an opening evening session talk at the Second International Conference on Sarcoma Biology on the cell of origin of embryonal rhabdomyosarcoma and undifferentiated sarcomas, while OHSU & the Pediatric Cancer Biology Program have had 3 well-visited posters (including one co-authored by Melissa Hill and our colleagues at the Northwest Sarcoma Foundation).

The Wayman Tisdale Story (osteosarcoma,basketball & jazz)

2011-10-21T22:41:00.012-07:00

Reposted from the Scott Carter Foundation website as written by Amanda.

Hollywood is coming to Holland Hall! On Saturday, October 29, 2011 the world wide movie premiere of the “The Wayman Tisdale Story” will take place at the Walter Arts Center at Holland Hall. The film celebrates the life and legacy of three time All-American, Gold Medal Olympian, NBA Star, World Renowned Jazz musician and Tulsan, Wayman Tisdale. The event is free and open to the public.

“The Wayman Tisdale Story” features never before seen interviews with Wayman Tisdale as he tells his own life story from childhood to his battle with Cancer. The film also features interviews with Michael Jordan, Sam Perkins, Toby Keith, Marcus Miller, Dave Koz, A.C. Green, Jonathan Butler, Steve McKeever, Billy Tubbs and the Tisdale family. Emmy nominated documentary director Brian Schodorf produced and directed the film and will be speaking at the premiere. The Los Angeles Times says “The Wayman Tisdale Story is a must-see film for all audiences.” View the trailer here.

The Scott Carter Foundation is excited to join forces with filmmaker Brian Schodorf to host the first public screening of “The Wayman Tisdale Story“. The event will be just like a Hollywood premiere–complete with a red carpet, photo ops, and the viewing of the hour long documentary. “The Wayman Tisdale Story” has been featured in multiple film festivals and has won numerous awards. It also features the song “Cryin’ for Me” which was written and performed as a tribute to Tisdale by Toby Keith.

Wayman Tisdale passed away in 2009 after a two-year battle with Cancer. He suffered from Osteosarcoma, a rare bone cancer, that also took the life of Tulsan, Scott Carter at age 13 in 1993. According to the American Cancer Society, each year about 800 new cases of Osteosarcoma are diagnosed in the United States. About 400 of these are in children and teens. Osteosarcoma is not a common Cancer and more research is needed. To date, the Scott Carter Foundation has raised $1.7 million for Children’s Cancer research. Read more about the Foundation here. “The Wayman Tisdale Story” premiere will take place at 7:30pm on Saturday, October 29 at the Walter Arts Center at Holland Hall, located at 5666 East 81st Street (Tulsa, Oklahoma). Doors open at 6:30pm. The event is free and open to the public. The Tisdale family, Director Brian Schodorf and the Carter family will be available for interviews. A copy of the movie is available upon request.

now available from e-bookstands: The Miles Levin Story

2011-10-21T12:02:00.001-07:00

reposted from levinstory.com

Miles Levin, a gifted but unfocused teenager from suburban Detroit – whiling away hours on videogames – is jolted by a diagnosis of a deadly cancer. Working out his feelings in writing on a blog, his charm, humor, spirit, and unceasing honesty drew the attention of readers from around the world. You - as have tens of thousands of others - will be amazed, humbled, and helped by what he wrote as he struggled with the hardships destiny imposed on him. Bob Woodruff, ABC news journalist, said of Miles, “He has told us what it means to live life without fear, but with Joy.”
While most of Miles’ days were challenging, some were filled with the happiness every teenager hopes to have – the thrill of first love, the fun of prom night, and the caring and admiration of friends. Cancer was bringing an end to his life, but he brought completion to his life. In so doing he inspires us to be mindful, loving, joyful, and thankful. He left us an enduring gift, thereby fulfilling his greatest desire when he wrote: “Dying is not what scares me; it’s dying having had no impact.”

The link to the e-bookstands wesbite for this book is here.

Whose data?

2011-10-20T10:40:00.001-07:00

For an interesting concept, see Sage Bionetwork's website on a new trend for patients to have access to data generated from their own samples. Quoting, "Key objectives: Enable patients to obtain their own data back from samples they donate to trials". A very provocative idea!

Leaving a Legacy - the value of tumor tissue from Autopsy

2011-10-19T12:58:00.006-07:00

While a difficult topic, there may be times where a cancer death can have more meaning by improving knowledge of the disease through tissue donations after life. For the first in a series of publications related to childhood cancer 'Legacy Gifts', see our co-authored paper in the journal Cancer entitled, "The clinical, research, and social value of autopsy after any cancer death: A perspective from the Children's Oncology Group Soft Tissue Sarcoma Committee".

More information can also be found at www.ccurefast.org or our partner website at the Northwest Sarcoma Foundation. See also our PCB related blog entries on this topic.

OPEN SCIENCE FORUM: (updated 12/05/2011, with comments welcome!)
Below are our academic-community team's intended project milestones for defining a path to survival for the most incurable childhood cancers:

begin national dialogue with pediatric oncologists about the topic.

Legacy Gift Workshop presented at Fall 2011 Children’s Oncology Group (COG) meeting, in partnership with two Sandy Smith and Kim Spady, who themselves are cancer survivors presented their families experiences with tissue donation after their sons passed away from brainstem gliomas. Sandy and Kim are passionate supporters of families on this topic, and have first-hand experience facilitating these types of tissue donations after life (at autopsy).

understand and publish the potential barriers to autopsy as understood from interviews of families conducted under our NCI-funded project, NIH/NCI R01CA133229-04S2.

This study is the successor to the position paper we published for the COG Soft Tissue Sarcoma committee:

Sheri L. Spunt, Sara O. Vargas, Cheryl M. Coffin, Stephen X. Skapek, David M. Parham, Joan Darling, Douglas S. Hawkins, Charles Keller. The Clinical, Research, and Social Value of Autopsy after Any Cancer Death: A Perspective from the Children’s Oncology Group Soft Tissue Sarcoma Committee. Cancer, 2011 Oct 17 epub [PMID 22006470]

create a shift in culture among medical care providers by seeking to have an educational session on how to approach the topic of autopsy with families at the COG Fall 2012 meeting.

This is a successor to the Fall COG 2010 workshop, OVERCOMING AUTOPSY BARRIERS IN PEDIATRIC CANCER RESEARCH: Providing Hope For Tomorrow’s Cures described above.

optimize www.ccurefast.org to work in parallel with other websites such as kidsvcancer.org, having peer education & caregiver guidelines as well as assistance for families via an online single-point-of-contact.
write a Children’s Oncology Group autopsy banking protocol for all childhood cancers by multi-institutional collaboration by Spring 2012.

All specimens would be sent to the COG Biorepository in Columbus, Ohio.
Access to any specimen in the COG Biorepository would require COG disease subcommittee scientific peer review to ensure the study request was scientifically rigorous and used only the amount of sample absolutely required (in order to increase the number of studies per tissue collection).

seek a foundation that would help fund the costs of autopsy collection kits, as well as a reimbursement to COG institutions for the logistics of packaging and shipping autopsy collections by Summer 2012.
encourage broad use of these highly valuable, high informative tissue specimens starting Fall 2012 so that the 1 in 5 children not cured of cancer may someday survive his/her cancer.

01/09/2011: manuscript for the NCI-funded study of autopsy barriers to be submitted today.

our approach to Personalized Cancer Therapy

2011-10-19T11:33:00.001-07:00

Many thanks to the team and to the patients that helped created this first video version of our vision for personalized cancer therapy. The approach will probably be moved from canine patients to human patients in the context of relapsed disease. It's certainly something we are moving ahead as quickly and as carefully as we can. A high resolution of our video can also be found here.

DVM360 on Canine Osteosarcoma Trial

2011-10-07T22:13:00.000-07:00

For more on the OHSU - OSU collaboration, click here .

ABC2 Summit in Sausalito

2011-09-30T15:40:00.000-07:00

The last 2 days leaders in glioblastoma research have met in a special, collaboration-promoting summit sponsored by Accelerate Brain Cancer Cure (ABC2). Highlights include understanding the influence of metabolism on glioblastoma tumor cell fitness, the mechanism of action of thalidomide, and more. By far, the best aspect of this project was the community involvement (hence, accountability for collaboration) and the industry - academic interface that this environment creates. A very significant industry interest was expressed in DIPG (pontine gliomas). More news to come...

Many thanks to Max & David of ABC2 for creating such a rich environment for collaboration. To learn about the life of Dan Case and the creation of ABC2, click here.

Rhabdomyosarcoma Research presented in Ascona

2011-09-22T15:16:00.000-07:00

We are grateful to Denis Guttridge (Ohio State), David Glass (Novartis) and Markus Ruegg (University of Basel) for the opportunity to present our work on the epigenetic determinates of rhabdomyosarcoma at the 2011 International Conference on Molecular Mechanisms of Muscle Growth and Wasting in Health and Disease. Our laboratory's work was very well received, and new collaborations were established that take us into new, exciting multidisciplinary areas.

[ The conference was sited at Centro Stefano Franscini in Ascona, Switzerland (pictured). ]

Personalized Medicine Talk with Georgetown Colleagues

2011-09-09T21:44:00.000-07:00

We are grateful to Dr. Aykut Uren and colleagues including Todd Waldman and Jeff Toretsky for the opportunity to present our research and approaches to personalized cancer therapy as part of the the Georgetown University Hospital/Lombardi Cancer Center visiting professorship series. The ideas exchanged bring both groups closer to our goal of improving survival for the 1 in 5 children for which current therapy is yet not sufficient for long term survival.

Update on the Personalized Cancer Therapy Trial - for Canine Osteosarcoma

2011-09-01T20:45:00.004-07:00

Congratulations to Lara on an excellent research-in-progress presentation at the Annual OHSU-DCH Pediatric Fellows Research Conference. This Phase II clinical trial for dogs with osteosarcoma opened 2 weeks ago. The early success of this collaboration is a large part attributable to the strong collaboration with Dr. Bernard Seguin at Oregon State University Veterinary Hospital and lab members and alumni, Jinu and (especially) Nicolle, respectively.

Scott Carter Foundation Big Show!

2011-08-28T06:36:00.000-07:00

Last night in Tulsa was the Scott Carter Foundation Big Show! that precedes the annual golf tournament fundraiser. Scott was a young boy who had osteosarcoma, but without regard for himself he was passionate that other children like his friend Addie should have better available treatments. He created an effort to raise money for childhood cancer research, and in his memory Scott's family and community annually raise funds that support the training of new research scientists, which have included Charles more than a decade ago, as well as our own lab's recent graduates: Koichi Nishijo, Jinu Abraham and Nicolle Hofmann. We are grateful to the Scott Carter Foundation for their support of our trainees and our research on sarcomas, including osteosarcoma.

[ right, John Grant mc'g the auction; left, Charles and Paul 'Ole Dad' Compton, Scott's grandfather. ]

Collaborator, Dr. John Ohlfest

2011-08-18T11:18:00.000-07:00

For a summary from Minnesota Public Radio on the promising tumor immunology approach of brain tumor researcher, Dr. John Ohlfest, click here.

Patrick M. Callahan Memorial Fund

2011-08-03T08:40:00.000-07:00

Our thanks go to the generous support of the family and community of Patrick Callahan, in whose memory Patrick lives on despite the 15 month battle with metastatic alveolar rhabdomyosarcoma that claimed his life at age 24. Patrick is remembered as a smiling and joyful young man (and dedicated Phillies fan), and it is in this spirit that "Patrick's Team" of Elaine and Janelle are pursuing a research project sponsored by the PMCMF to understand the process of alveolar rhabdomyosarcoma metastasis.

Jared's Juggernaut to Cure Sarcoma

2011-07-26T22:01:00.002-07:00

We are sincerely grateful to Robyn Grossman and the community supporting Jared's Juggernaut to Cure Sarcoma for their recent, generous gift to support research of rhabdomyosarcoma. Jared was no stranger to challenges, making his way through adolescent and young adult life despite learning disabilities by graduating high school a year early and achieving a 3.4 college GPA (despite a 5 year battle with rhabdomyosarcoma). Jared was the best in us, and the inspiration to do more than we think is possible. Through the research support provided in his memory, we will work towards developing new rhabdomyosarcoma cell cultures enriched in tumor stem cells, and we will perform molecularly-targeted drug screen testing specifically of these metastasis-prone cells. This work will be done by our lab members Emma (left) and Jen (right), who will be "Jared's Team".

Wesley’s Cure for Cancer Research Foundation

2011-07-18T22:28:00.002-07:00

We are grateful to Matthew Nelson and the Wesley’s Cure for Cancer Research Foundation (WCCRF) for their recent generous donation that fuels our medulloblastoma cancer research. Inspired by the experiences of a young neighbor going through treatments for this aggressive brain tumor of childhood, Matthew created this grass-roots effort to honor Wesley and create hope that more effective, less toxic treatments might one day be available. 'Welsey's Team' in the Keller laboratory will use these funds to help test new, molecularly-targeted drugs for high risk and recurrent medulloblastoma.

[ "Wesley's Team" left to right: Elaine (PPTI operational manager), Jinu (PPTI scientific manager), and Melanie (medical student and Summer research intern) ]

Children's Healing Art Project

2011-07-18T22:18:00.000-07:00

We are thankful to the Children's Healing Art Project for providing us artwork from childhood cancer patients for our laboratory. The CHAP mobile teaching artists do wonderful things for children to help them express their feelings on their journey through cancer treatment, and at the same time we get this great art! Shown to the right is our microscope room, for which we needed to block light through a window... now we have an inspiring set of images as we go to do our our work.

Schmidt Laboratory Retreat

2011-07-11T08:20:00.000-07:00

It was a pleasure to spend the past few days with liver biologist and fellow Capecchi lab alumnist, Ed Schmidt, and his lab, colleagues and family for a backcountry Montana retreat (hiking and camping trip, complete with pack donkeys). And yes, when scientists go camping we do talk a lot of science :) but the kids also get a special set of 'guides' to nature.

Our thanks to the Thrasher Foundation

2011-06-17T20:07:00.000-07:00

We are grateful to the Thrasher Foundation for the Early Career Award to our AYA Fellow, Lara Davis. Her project, "Translating ex vivo osteosarcoma targeted drug sensitivity into improved survival" investigates personalized cancer therapy for this adolescent and young adult cancer - using pet dogs that spontaneously develop osteosarcoma as a model. Thrasher Foundation has a long tradition of funding pediatric medical research, in the tradition of its founder E.W. "Al" Thrasher.

Congratulations, Lara!

Welcoming Janelle

2011-06-09T21:53:00.000-07:00

We are excited to Welcome Janelle Myers to the Keller Laboratory as a Summer internship student. With one year left to finish an undergraduate degree in integrated science and chemistry at Northwestern University, Janelle is here to get a rich experience in biomedical research (one of her many possible career paths). Janelle remarks that she still doesn't have an answer to the eternal questions about what she wants to do with her life--subatomic physics, nutritional chemistry, and French cuisine (she spent the last nine months in Strasbourg) are all vying with cancer biology. A Portland native, Janelle says she is happy to be back in the city of roses and is looking forward to a great Summer.

Tandutinib in Medulloblastoma

2011-06-07T09:28:00.000-07:00

Congratulations again to Sachiko and Monika on their recent manuscript acceptance and upcoming publication in the Journal of Pediatric Hematology and Oncology addressing the therapeutic role of Tandutinib (MLN518) in medulloblastoma. Co-authors include fellow lab members Sangeet & Jinu and lab alumni Suresh, Laura and Aoife. Collaborating co-authors are Brian Rubin (Cleveland), Marti Hanes (San Antonio) and Frank Giles (Galway, Ireland).

Outrunning Cancer - a Runner's World story

2011-06-04T00:40:00.001-07:00

[ from the Northwest Sarcoma Foundation Newsletter ]

The July issue of Runner's World magazine highlights Serena Burla, an elite runner, and her personal story of her fight against synovial sarcoma. The Runner's World special, Outrunning Cancer, includes "over 40 pages of content on the powerful link between running and cancer and how running races to benefit cancer charities has become a critical fundraising tool for charities" like the Northwest Sarcoma Foundation.

To read more about Serena and her amazing story visit:

http://www.runnersworld.com/article/1,7120,s6-243-588--13970-0,00.html

Welcoming Graduate Student, Rebecca Smith

2011-05-30T21:49:00.014-07:00

We are excited to have rotation student, Rebecca Smith, join our lab team this Summer.

about Rebecca in her own words:
... with a BA in English and French (University of Illinois at Urbana-Champaign) and an MA in 18^th Century British Literature (University of Michigan—Ann Arbor), I often get perplexed stares when I say I am starting a PhD in biosciences. After spending 12 years at home raising my twin daughters and deeply entrenched in community volunteering, I started searching for something intensely fulfilling to satisfy the professional hole in my life. I begin taking basic science classes with the idea of going to medical school. Along the way I was awarded an internship in the lab of Dr. Stephen Lloyd (OHSU) in which I got my first real taste of research. I then pursued a volunteer position in the lab of Dr. Thomas Scanlan (OHSU) and have spent approximately 7 months working nearly full time. Dr. Keller interviewed me when I sought admission to the PhD program (PMCB), and it was clear to me that this lab would provide challenge, stimulation, and opportunity. I am grateful for a summer rotation and will focus both on learning new protocols and the science behind them and contributing to the lab’s research through my work.

We are honored to have Rebecca and her inquisitive nature added to our team!

Scott Michael Carter Memorial Lectureship

2011-05-28T23:31:00.000-07:00

For the News blog entry from the Scott Carter Foundation, click here. For the Pediatric Cancer Biology Program blog entry, click here.

Rally Foundation funds Undifferentiated Sarcoma Research

2011-05-25T21:23:00.000-07:00

We are grateful to the Rally Foundation for a grant of $25,000 to fund our PPTI research project, Targeted Therapy for Undifferentiated Sarcomas. This award is in honor of a little 4 year old girl named Ava whose life was interrupted by this same cancer. We hope to understand this rare kind of cancer, and to develop non-chemotherapy approaches that are life sustaining for future children who may face the same challenge.

Congratulations, Sachiko and Monika !

2011-05-22T23:06:00.002-07:00

Through careful, systematic investigation the work on the mechanism of proteosome inhibitor efficacy in medulloblastoma has been accepted for publication in the Journal of Neuro-Oncology. As a matter of full disclosure, the lead to an important facet of this paper was in fact suggested by a Reviewer! This study is co-first authored by Monika and Sachiko. Other authors include Keller lab alumnists Tohru and Laura.

This work was supported by a research grant from the National Brain Tumor Society.

[ 6/5/2011 update: the paper is now online at here ]

Welcoming Emma!

2011-05-22T09:26:00.000-07:00

We are excited to welcome recent college graduate Emma Cantor to our team! Emma brings with her rich experiences in molecular biology research as a college student, medicosocial outreach to the youth community and pediatric and cancer care exposures. Emma's Summer internship will include participation in the Childhood Cancer Registry for Familial and Sporadic Tumors [CCURE-FAST] tumor bank & registry as well as preclinical therapeutics studies.

in Emma's own words:

"My interest in pediatric oncology began during my high school years when I worked as a child life volunteer in the Children’s Hospital of Philadelphia Cancer Center. Since then, I have continued to explore my interests in both medicine and pediatrics through EMT training and work as the Chief Pediatric Emergency Medicine Research Associate in the St. Louis Children’s Hospital. After just graduating from Washington University in St. Louis (May 2011) with a BA in Biology and Anthropology, I am excited to return to my roots in the Northwest to join the Keller Lab."

In Appreciation: Douglas Church

2011-04-12T21:21:00.000-07:00

Tireless is often a figurative term, but in Doug's case it can be a literal adjective. Our lab team often comes in for a 'second shift'. But we're often not the only ones up in the Biomedical Research Building... Tonight, 9:13pm, as usual -- Doug is still doing his first shift... and a very long one at that! Doug is a key administration and grants person who strives for excellence, and it shows not only in his hours but also the quality of what he does.

Thank you, Doug!

Congratulations, Tohru !

2011-04-08T10:45:00.002-07:00

Many congratulations to Tohru that his study of the role of the Rb1 gene in muscle stem cells has been accepted for publication in The Journal of Biological Chemistry. This particular study was a lot of work, and it is the third paper by Tohru from his postdoctoral fellowship in our laboratory (the other in press & recent in print studies were on the muscle cancer rhabdomyosarcoma and a strangely muscle-like ontogeny of pituitary progenitor cells). Tohru is truly a scientist for all seasons.

Co-authors of the JBC study include current KellerLab member, Guangheng Li, as well as KellerLab alumnists Suresh Prajapati and Koichi Nishijo.

[ Pictured to the right is Tohru with his wife, Dr. Sachiko Ohshima-Hosoyama, who also is a KellerLab alumnist. ]

[ now Online! click here. Print publication will be June 3. ]

Welcoming Sangeet

2011-04-07T09:20:00.001-07:00

We are excited to welcome postdoctoral fellow, Dr. Sangeet Lal, to the Keller laboratory. Sangeet brings expertise in malignant glioma tumor microenvironment and unique animal model to our laboratory & program.

An introduction in Sangeet's own words,

" My first exposure to basic science research happened during my M.Sc. at I.I.T., Bombay,

India

, and my interest in this career matured during my tenure as a research assistant at ICGEB,

India

. I want to establish my research career in developing tumor cell-specific targeting strategies. During my doctoral training in Jeffrey Greenwood’s lab at Oregon State University, I developed my knowledge of cancer cell biology while studying the mechanisms regulating invasion of glioblastoma cells using transparent zebrafish as in-vivo and organotypic mouse brain slices as ex-vivo approaches. My post-doctoral research in Dr. Keller’s lab will focus on investigating factors responsible for leptomeningeal metastasis in pediatric brain tumors. "

We're very glad to have Sangeet on our team!

AACR Annual Meeting

2011-04-04T19:36:00.001-07:00

Today at the American Association for Cancer Research in Orlando, Ken presented his poster on The role of protein kinase Cι in alveolar rhabdomyosarcoma. Charles also began his term on the tumor microenvironment (TME) steering committee.

An emerging theme is that targeted (non-chemotherapy) drugs probably need to be given in combination for most solid tumors, and that the complexity of cancer and nearby non-cancerous tissue needs to be considered for targeted treatment, too.

COG Brain Tumor Preclinical Symposium

2011-03-27T16:48:00.000-07:00

Our thanks to all the speakers and thought leaders that participated in the COG-CNS Developmental Therapeutics (DVL) Symposium on Friday. This Children's Oncology Group special science symposium on childhood brain tumors was designed to bring together scientists and clinicians to create systematic approaches to integrating recent advances in brain tumor research and newly emerging preclinical resources to create tangible, actionable 6 month milestones. Organizers included Amar Gajjar (St Jude; Chair of COG-CNS cmte), Maryam Fouladi (Cincinnati Children's Hospital; co-chair CNS-DVL) and Charles Keller (OHSU; co-chair of CNS-DVL). Speakers were Jim Olson (Univ of Washington/FHCRC), Anita Hjelmeland (Lerner Institute/Cleveland Clinic), Xiao-Nan Li (Baylor/Texas Children's Cancer Center), Anang Shelt (St Jude), Clinton Stewart (St Jude) and Richard Gilbertson (St Jude). Particularly impressive were the special pharmacokinetic models from Dr. Stewart, the new preclinical models from Dr. Li, and the outstanding eppendymoma science from Dr. Gilbertson. It was an active session with important ideas from many thought leaders across North America, and importantly, an inclusive plan is in place to bring new drug (and new drug combinations) into effect for the most devastating of childhood brain tumors.

Imran selected as a 2011/212 HHMI Fellow

2011-03-18T20:22:00.002-07:00

Many congratulations to Imran Alsam who has been selected as a Medical Research Fellows Program of the Howard Hughes Medical Institute. This unique and prestigious program permits high-achieving medical students to take a year away from medical school to conduct focused research. For his year, Imran will work on tumor cell evolution in a collaborative project between the Keller and Druker laboratories.

  Congratulations again, Imran, on this great achievement along your path to becoming leading physician-scientist!


[ update 7/17/2011: Imran was highlighted in the AMA Foundation June e-news! ]

Congratulations, Tohru and Imran !

2011-03-07T12:35:00.001-08:00

We are excited that Tohru and Imran's study of IL-4 Receptor as a therapeutic target in rhabdomyosarcoma has been accepted for publication in the journal, Clinical Cancer Research. Co-authors include PPTI Scientific Manager Jinu Abraham, as well as lab alumni Suresh, Koichi and Laura. Collaborator co-authors are Lee Ann Zarzabal & Joel Michalek (UTHSCSA), Denis Guttridge (Ohio State) and Brian Rubin (Cleveland Clinic). This work was funded in part by the Scott Carter Foundation, the AMA Foundation, the Joanna McAfee Childhood Cancer Foundation and the National Cancer Institute.

[ update 5/11/2011: view the article online here. ]

Welcoming Lara !

2011-02-15T11:29:00.000-08:00

We are excited to welcome physician-scientist trainee, Dr. Lara Davis to the Keller laboratory. Lara is one of those rare physicians who will be qualified to treat both child and adult cancer patients.

in Lara's words:

After graduating from Wellesley College with a BA in Neuroscience, I attended medical school at OHSU where learning about new targeted therapies such as Gleevec sparked my interest in oncology early on. During medical school, I found myself enjoying caring for both children and adults with cancer and thus decided to pursue residency training in Med-Peds. I completed the four-year training in the Harvard Med-Peds Program at Brigham & Women’s Hospital and Children’s Hospital Boston and am now board certified in both Internal Medicine and Pediatrics. My interest in oncology evolved throughout residency to a focus on adolescents and young adults (AYA), an often over-looked population. I worked with Dr Linda Stork and Dr Brandon Hayes-Lattin to design a combined fellowship at OHSU and am now completing my second clinical year (one in peds hem/onc, one in medical onc). This summer I will join the Keller lab to pursue my interest in identifying targeted therapies for cancers that disproportionately affect AYA patients, particularly sarcomas.

We are thankful to have such a talented young person join our team. We fully expect that Lara will be a future leader in personalized medicine for sarcomas, particularly osteosarcoma.

Rhabdomyosarcoma Study published in Cancer Cell

2011-02-14T09:01:00.008-08:00

In a report published today as the Featured Article in the journal Cancer Cell, investigators at the Oregon Health & Science University (OHSU) reveal interesting new findings for a kind of cancer called sarcoma. The most common sarcoma of children occurs in the muscle and has an appearance of muscle (rhabdomyosarcoma). In adults, sarcomas are often even more primitive appear (undifferentiated pleomorphic sarcoma). In their report, the Keller Laboratory reveals that childhood and adult sarcomas are linked in their biology, mutations and the cells from which these tumors first start.

Childhood muscle cancer, or rhabdomyosarcoma, is a condition that when spread throughout the body leads to a low survival rate – only 20 – 40%. In adults with soft tissue sarcomas, survival can be even lower. Now, for the first time, scientists and doctors know from where these tumors arise and what drives them to grow and spread. Armed with this new information, the researchers in the Pediatric Cancer Biology Program at OHSU are looking for ways to stop or eradicate these sarcomas.

“A commonly held belief is that cancers should be cut out, burned out or killed. There is a fourth option – to have cancer cells choose to become normal cells, in this case muscle cells,” says Dr. Keller, who led the study. “A least for a subset of patients, possibly the ones with hereditary cancer, one approach suggested by our research might be to administer drugs that muscle cancers to convert into non-cancerous muscle fibers. This is a minority opinion, but one held by a small group of careful scientists throughout the US and abroad.”

The survival rate for childhood muscle cancer that has spread has remained unchanged for more than 40 years. It has reached the point that increasing the intensity of chemotherapy, radiation or surgery is no longer having any improved effect. A novel approach taken by Keller and his colleagues in the laboratory as well as in new clinical trials is to use non-chemotherapy medicines to inhibit “molecular targets” such as growth factor receptors in this disease. Suman Malempati, Director of the Oncology Developmental Therapeutics Program at OHSU’s Doernbecher Children’s Hospital, is the lead on a national clinical trial of one such growth factor inhibitor. This study is the first trial to incorporate a molecularly-targeted drug into a clinical trial for childhood muscle cancer for the Children’s Oncology Group/Curesearch, a nationwide network of hospitals, doctors and leading scientists that develop new treatments for childhood cancer. This type of therapy tailored to a cancer’s mutation was first pioneered at OHSU by DeBakey-Lasker Award Recipient, Dr. Brian J. Druker. Dr. Druker and his colleagues developed a non-chemotherapy pill, Gleevec, which when taken each day causes a form of blood cancer, chronic myelogenous leukemia, to remain dormant indefinitely. Personalized Cancer Care for children and adults is the primary mission of the Knight Cancer Institute at OHSU.

We are grateful to the Scott Carter Foundation for the fellowship support of Jinu Abraham and Koichi Nishijo that has made these studies possible.

For the Preview commentary, click here.
For the Article itself, click go to the main page or here.

Congratulations, Suresh !

2011-02-01T12:31:00.000-08:00

Congratulations to Suresh whose study, "Contrast Enhanced Vessel Imaging using MicroCT" was just published in the Journal of Visualized Experiments. This study was nearly entirely written and executed by Suresh in the same month that our laboratory moved from Texas to OHSU. Suresh is a standalone expert in the field of small animal imaging, and it is our great pleasure to have had him as a key member of our team for so many years. Not only is the technique presented by Suresh from our lab's work important in the study of genetically-engineered mouse models of cancer, but the journal format in which it is presented, a full video production, is an important new approach to sharing information and expertise about techniques.

Again, Suresh, many congratulations!

Congratulations, Jinu !

2011-01-31T10:07:00.003-08:00

Congratulations to Jinu, whose first author paper on drug resistance to Igf1 Receptor inhibitors was accepted today to the journal, Molecular Cancer Therapeutics. This study is of relevance to a Children's Oncology Group study run by OHSU co-author Dr. Suman Malempati, who is investigating Igf1 Receptor inhibitors in metastatic rhabdomyosarcoma. Other key contributors included Suresh Prajapati, Koichi Nishijo, Beverly Schaffer, Eri Taniguchi, Aoife Kilcoyne, Amanda McCleish, Laura Nelon and Frank Giles (UTHSCSA), Argiris Efstratiadis (Academy of Athens), Robin D. LeGallo (University of Virginia), Brent M. Nowak (UTSA) and Brian Rubin (Cleveland Clinic). Different aspects of this study were funded by the Scott Carter Foundation, Alex's Lemonade Stand Foudnation, Hyundai Hope on Wheels Program and the National Cancer Institute.

Nicely done, Jinu!

[ 4/11/2011: Jinu's paper is the cover article for April. ]

Dog Osteosarcoma Project

2011-01-28T21:14:00.003-08:00

We couldn't be more excited about the advocacy of our collaborator, Dr. Jeffrey Tyner, in presenting our multi-institution research program to identify better treatments for pet dogs that develop osteosarcoma. Jeff is a member of the Druker laboratory, and a key project contributor for this important initiative to understand childhood and canine osteosarcoma. The video on Fox News can be seen here. Other collaborators on this project include Oregon State University veterinary faculty Bernard Séguin, Shay Bracha, Stuart Helfand and John Mata; OHSU Epidemiology faculty Thuan Nguyen and Motomi Mori; Doernbecher Pediatric Oncology faculty Suman Malempati; Bioinformatics specialist Ranadip Pal; Druker laboratory member Marc Loriaux; and of course the core team in the KellerLab who drive this Pediatric Cancer Biology Program project: Nicolle Hofmann and Jinu Abraham, with the aid of Elaine Huang and incoming med-peds fellow, Lara Davis.

McAfee Foundation funds Preclinical Therapeutic Study for Alveolar Rhabdomyosarcoma

2011-01-07T19:28:00.002-08:00

We are grateful to the Joanna McAfee Childhood Cancer Foundation for their unwaivering 3nd grant to our lab in the amount of $15,000 to evaluate a novel new compound for efficacy in a genetically-engineered mouse model of alveolar rhabdomyosarcoma. This study is done as part of the Pediatric Preclinical Testing Initiative at the our institution... an effort to speed discovery of clinically-feasible agents that can be moved to clinical trials for childhood cancer. This work is done in the spirit of helping children like Joanna Rae McAfee, who faced the tremendous challenge of this disease and whose memory lives on to inspire research teams and communities to work together in making rhabdomyosarcoma a uniformly curable disease.

Funding from the JMCCF is raised with such grass-roots efforts as the annual Macy Easom Memorial Charity Golf Tournament. Macy was a young girl who, like Joanna, lost her battle against childhood cancer. Macy's parents and Joanna's parents (along with help from an amazing community of volunteers) organize this annual benefit to raise awareness and to provide tangible support to families of children currently going through their own treatment. To see what an amazingly pro-active group the JMCCF represents, visit their Events page for a list of presentations and fundraising activities over the past year. Simply amazing.

click below to see the results of our prior JMCCF-funded research!

Congratulations, Monika!

2010-11-27T10:09:00.000-08:00

Many congratulations to Monika, whose publication from earlier work in the Soderling Lab on medulloblastoma migration has recently been released for early electronic publication in the Journal of Neuro-Oncology. This thoughtful paper on mechanisms of medulloblastoma migration also takes a look towards pharmacological inhibition, a step towards addressing leptomeningeal metastasis.

Rebecca and Sada Tarshis Endowed Professorship

2010-11-24T07:13:00.016-08:00

It is an privilege and honor to be a steward of the Rebecca and Sada Tarshis Endowed Professorship. These two sisters came from a modest background as children of immigrants from Russia, yet by building careers and living well, though judiciously, created a legacy that continues to benefit the Portland greater community. I hope that through the work of our laboratory and the Pediatric Cancer Biology Program that we will meet the example of bringing forth tangible change and contributing to the greater good, particularly with respect to outcomes for metastatic childhood cancers.

-- Charles

[ above right: Charles with Elaine, who is holding 'the chair'. For the SOM Newsletter article, click here. ]

Visiting Scientist, Tohru Hosoyama

2010-11-06T14:55:00.001-07:00

We were honored to have lab alumnist Tohru Hosoyama visit our lab in Portland this past week. Tohru is now a fellow in the laboratory of Dr. Masatoshi Suzuki at the University of Wisconsin in Madison. Tohru is no doubt a rising star to watch in the muscle stem cell biology field.

[ above right: Tohru with lab members Monika, Charles & Jinu ]

Welcoming Guangheng !

2010-10-15T13:26:00.002-07:00

We are excited to welcome surgeon-scientist Dr Guangheng Li the Keller laboratory. 'GH' received his M.D in 1996 from Henan Medical University and his Ph.D in 2002 from the Shanghai Second Medical University. As a member of the Stem Cell Research Center in the Department of Orthopedic Surgery at University of Pittsburgh, GH authored or co-authored numberous tissue engineering and stem cell studies that have been published in the Journal of Tissue Engineering, Journal of Bone and Mineral Research, Nature Biotechnology, and Arthritis and Rheumatism. His research has focused primarily on using gene therapy, skeletal muscle stem cell and protein therapy to improve bone healing and delay the process of joints disease. In the Keller laboratory, GH will extend these interests to the study of activated muscle stem cells and muscle cancer (rhabdomyosarcoma).

Pediatric Cancer Biology Strategic Planning Retreat

2010-10-03T21:40:00.002-07:00

We thank the leadership and key members of the OHSU Division of Pediatric Hematology-Oncology, as well as our partners from the Doernbecher Children's Hospital Foundation for attending this Fall's first annual strategic planing retreat for the OHSU Pediatric Cancer Biology Program. The retreat met yesterday at Skamania Lodge in the Columbia River Gorge. The event was moderated by Dr. Cory Hallam, Director of Commercialization Alliances and Innovation as well as the Center for Innovation and Technology Entrepreneurship (CITE) at the University of Texas at San Antonio. It was a very productive day, with the only caveat that we were indoors nearly the entire time, whilst it was a beautiful day outside. Still, it was a tremendously valuable activity and will lead to a highly specific strategic plan to be generated in the coming weeks.

[ credits and thanks to Dr. Linda Stork for the Gorge photo ]

Hyundai Hope on Wheels funds Rhabdomyosarcoma study

2010-09-29T23:06:00.001-07:00

We are grateful to the Portland area and national Hyundai dealers who so graciously fuel the Hyundai Hope on Wheels program to fund childhood cancer research across the nation. Our laboratory yesterday received a generous award of $100,000 to study the response of alveolar rhabdomyosarcoma to growth factor inhibitors... and to determine the mechanisms by which such strategies might be improved to prevent relapse and inhibitor resistance. We are all also very humbled by rhabdomyosarcoma patient, Josh Flanery, who took his time to talk with the group about his own experience with adolescent and young adult cancer.

YouTube video: http://www.youtube.com/watch?v=VxOlgtbd5Z0

Fox News coverage: http://www.kptv.com/local-video/index.html?grabnetworks_video_id=4353023

Exciting New NCI Award

2010-09-25T12:28:00.000-07:00

We are thankful to be one of a handful of recipients of an R01 supplement exceeding $200k in response to the Carolyn Price Walker Act. This award to our laboratory and the Northwest Sarcoma Foundation is meant to increase awareness of the improved outcomes of childhood cancer patients when treated at specialized, multi-disciplinary centers. We also have a project to increase awareness of the value of biopsy samples for scientific research when tumors grow despite treatment. Many thanks to the great number of people on the team at Doernbecher Children's Hospital, Melissa Hill at the Northwest Sarcoma Foundation, and Nancy Goodman of Kids vs Cancer for making this possible.

COG Fall Meeting

2010-09-25T00:20:00.005-07:00

This past week was the Children's Oncology Group Fall meeting. Normally, the COG meets twice a year to discuss design and results (when available) of the latest clinical trials. This was a particularly special meeting, in that founding COG Chair, Dr. Gregory Reaman, was recognized for his phenomenal legacy of work with COG & CureSearch, and physician-scientist Dr. Peter Adamson took the leadership position moving forward. This meeting was well attended by pediatric oncology medical caregivers and the public alike. Our lab's contributions were a rhabdomyosarcoma presentation to the Soft Tissue Sarcoma Biology Special Session, as well as chairing (with the help of Maryam Fouladi) the CNS new therapeutics session.

[ above right: Charles and Ross Vick, advisory director member of QuadW, discussing sarcoma research ]

Legislation and Childhood Cancer

2010-09-12T21:33:00.005-07:00

Groups like CureSearch, foundations and individuals approach childhood cancer advocacy through hard work in lobbying for executive and legislative initiative that improve the research and care of childhood cancer patients. One example is that September is "Childhood Cancer Awareness Month" by Presidential Proclamation. Nancy Goodman is a childhood cancer parent and founder of KidsvCancer.org who regularly lobbies on behalf of childhood cancer causes. Another advocacy group for increasing drug availability for cancer patients is the Abigail Alliance. These groups certainly deserve our thanks and support in their efforts.



[ 9/15/10 For a touching story about a little girl named Joanna whose memory is bringing awareness and rallying a community around childhood cancer patients, click here. ]

[ 9/16/10 See Nancy Goodman's testimony before the House at http://www.kidsvcancer.org/pediatric-cancer-caucus/ ]

speeding the pace of Phase I studies

2010-09-11T06:18:00.022-07:00

We'd like to acknowledge nurse Rae Acosta who is coordinator for the Pediatric Oncology Phase I program at Doernbecher Children's Hospital, with whom we team to design preclinical trials that address special populations of pediatric cancer patients most in need of drug development. Dr. Suman Malempati is overall leader of this COG-affiliated Phase I program, and it is the cross talk that we develop with Rae and Suman that makes what we do in the research lab seem all the more tangible.

[ above right: Jen (left) and Rae (right) next to some new equipment in the lab ]

The Seattle - Portland Connection

2010-09-10T09:13:00.000-07:00

We are grateful to the basic scientist and clinical researchers at the University of Washington, Seattle Cancer Care Alliance and the Fred Hutchinson Cancer Research Center for meeting with our OSHU team (Suman Malempati, Chris Ryan and I) to discuss areas of synergy between our research programs. We found strong common interests, particularly in the areas of (1) understanding how medulloblastomas grow and spread, (2) defining the basic biology of the differentiation defect for rhabdomyosarcoma and (3) translating recent studies of adolescent and adult sarcoma biology to clinical trials. The opportunity to explore immunotherapy for sarcomas is especially strong, too. We are thankful to the laboratories of Dr. Jim Olson, Dr. Stephen Tapscott, Dr. Michael Jensen and the clinical trials researchers Doug Hawkins, Robin Jones, Eve Rodler - and especially surgeon-scientist Chappie Conrad, for taking the time to explore and initiate these dual city collaborations in the Pacific Northwest.

Charles

Tissue Banking - Demystified

2010-09-01T18:33:00.000-07:00

A question sometimes asked is how research can be advanced, and contributing tissue to a tumor bank for research is a key element (money, yes, is nice... but high quality tissue from patients with tumors for which little is know is more valuable). And if it can be put in a gentle way, tumor tissue from the patients that researchers and clinicians so far have failed is the most valuable. That is, tissue from patients with relapses... even post-mortem biopsies from patients that have failed our best treatments.

How does one enroll to give tissue? In the case of soft tissue sarcomas, the Children's Oncology Group (COG) has had a tumor bank protocol called "D9902" open since March 1999. The consent form for this study is usually presented to families at the time a child is diagnosed and is being considered for a COG treatment study. Most people think of D9902 as a study for collecting tissue from the original untreated tumor, but... the protocol does already allow tissue to be collected from biopsies done at the time of relapse, as well as tissue taken after death (autopsies, partial autopsies and post-mortem biopsies). In practice, relapse samples rarely are collected (there are practical reasons not to subject children to extra procedures). Post-mortem samples are scarce... maybe none, with recent notable exceptions.

Where does the tissue go? well, a really good tumor bank! The COG contracts the Pediatric Cooperative Human Tissue Network (pCHTN) to store COG sample studies. Their Director is Dr. Nilsa C. Ramirez, and she and the Biopathology Center for the pCHTN are at the Nationwide Children's Hospital in Columbus, Ohio. Nilsa succeeds the late Dr. Stephen Qualman, who himself was taken by pancreatic cancer. Dr. Qualman was a leader in rhabdomyosarcoma pathology research, but Nilsa keeps this tradition in sarcomas strong, and she was recently joined by rhabdomyosarcoma researcher Dr. Peter Houghton who is building an exciting pediatric cancer research program at Nationwide.

What happens with the tissue? It gets used, hopefully! Dr. Stephen Skapek at the University of Chicago leads the Soft Tissue Sarcoma Biology subcommittee of the COG. Researchers send the pCHTN/COG applications to use the tissue. The applications are reviewed by Steve and others on his committee (such as myself). If the study looks promising, a few samples are sent. If the researcher shows promising results, many more samples can be sent. In fact, for the best studies we even consider, "emptying the bank". (important notes: the researchers only have de-identified samples... they won't know each patient's name. Also, statistical rigorousness is another important judging criteria for proposed studies).

How much does it cost? In theory, it shouldn't.... the tissue collection kits are meant to be a part of the existing COG D9902 protocol. However, there have been cutbacks in what the NIH/NCI gives COG for its studies. If there were a sudden 'flood' of samples, the pCHTN and I estimate it would cost $150 total (70 for the kit, 30 to ship the kit to the child's hospital, 50 to ship it back on dry ice). I've talked with a few foundations on whether they'd sponsor kits, and while we don't have any definite commitments, I think if the need arose we could find a way that patients wouldn't need to use their own money to contribute to research through the tumor bank.

I hope this helps with some of the questions arising lately. Feel free to comment on this blog or email me for more information.

Sincerely,
Charles

Welcoming Nicolle!

2010-08-31T15:49:00.001-07:00

We are proud to welcome Dr. Nicolle Hofmann to the Keller laboratory as our 2010/2011 Scott Carter Foundation Fellow at OHSU. Nicolle will be pioneering an osteosarcoma therapeutics study between OSU (Corvallis) and OHSU (Portland). To this project Nicolle brings a background in plant genetics, which is probably very appropriate for certain kinds of therapeutics we will be exploring.

Nicolle's bio, in her own words:

" I received my B.Sc. in Animal Sciences at the University of Illinois. After taking a couple years off from school to work as a research assistant in the Nutrition and Food Science laboratory of Dr. John W. Erdman, I went on to pursue a Ph.D. in Plant Breeding and Genetics. Since completing my Ph.D., I have held two post-doctoral positions, one in the Soybean Genomics and Improvement Laboratory at the USDA in Beltsville, Maryland and one in a plant metabolic engineering laboratory at Virginia Tech in Blacksburg, Virginia. Now that I am here in Portland, I am very excited to enter a very important area of research in the Pediatric Cancer Biology Program at OHSU."

Welcome, Nicolle!

Scott Carter Foundation Big Show! and Golf Tournament

2010-08-30T22:32:00.003-07:00

Jinu and I were privileged to attend and participate in the Scott Carter Foundation fundraiser events this weekend in Tulsa, Oklahoma. This is an all-volunteer driven two part event, the Big Show dinner and auction, and the Indian Springs Golf Tournament. It was my pleasure to meet the numerous proactive benefactors of the SCF in Tulsa, including some special parents of childhood cancer survivors including Amy White, a tireless advocate of families in her role as Pediatric Oncology Coordinator of the Oklahoma Family Network. In its 17th year, this event exemplifies the commitment of a Scott's Family, and his community, to honor his memory by building a stronger foundation of research in childhood cancers. We are grateful that Jinu could be the 2009/2010 Scott Carter Fellow at OHSU.

Charles

[ above right: John Grant, Paula Carter, Jinu Abraham ]
[ below right: Jinu Abraham, Cason Carter, Charles Keller ]

an informal word on our lab's research

2010-08-20T20:35:00.002-07:00

Our laboratory focuses on long term and near-term treatments for the childhood muscle cancer, rhabdomyosarcoma, and the childhood brain tumor, medulloblastoma. To say long term, we mean basic science investigation of how these tumors work – such things as what kind of normal cell gives rise to one particular kind of cancer. And in saying near-term, we mean finding molecules in these cancers to directly turn off or turn on by drugs so that the tumor stops growing. Behind both approaches are some rather exciting genetically-engineered mice… modified from before birth so that at a certain age, and in a certain tissue, the same mutations found in a child’s cancer are activated in the mouse. Then the tumor can be followed to see how it grows and spreads… even to test a treatment to see whether the tumor growth can be reversed. That these mice have normal immune systems is a real plus, too, because white blood cells play an important role in how tumors evolve and respond to therapy.

While this use of mouse models makes our lab slightly unique, our greatest asset is that we have a very multi-disciplinary team. Biomedical engineers for building and operating imaging and diagnostic instruments, biochemists for understanding the molecules, molecular biologists and electrical engineers for understanding how tumors express genes in certain ways, and me (the board-certified pediatric oncologist) helping bring it all together in a focused way. Sometimes we venture beyond the ordinary, such as the use of 26¢ fertilized quail eggs (instead of mice or petri dish experiments) to study anti-cancer drugs. That last project is one graciously sponsored by the Alex’s Lemonade Stand Foundation. We’re even the first to work with the National Cancer Institute’s Pediatric Preclinical Testing Program to try exciting new drugs right out of the pharmaceutical development pipeline in genetically-engineered mouse models of childhood cancer.

I’d like to think that tangibly better treatments for rhabdomyosarcoma and medulloblastoma can be found in a matter of years, instead of tens of years. I go to a fundraiser golf tournament for the Scott Carter Foundation every year. They sponsored my research training in Mario Capecchi’s lab years ago, and now sponsor our pediatric cancer researcher in training, Nicolle Hoffman. Standing at the 18th hole every year, I get the same question about every 5 minutes, “Doctor, do you have anything new for these kids yet?” These questions led my lab to put a heavy emphasis on therapeutics about 4 years ago. As a result, we’re finding drug targets, as well as drugs to hit those targets that are less inclined to result in relapse for our patients (ok – yes, it’s just mice so far, but I also am a member of the Children’s Oncology Group committee that designs COG trial for rhabdomyosarcoma).

What's on the horizon? A lot! In moving to OHSU in Portland we're now teaming with Dr. Brian Druker to develop personalized targeted therapies (of the non-chemotherapy variety) for children with cancer. Our results can move faster than ever from the bench to the bedside with the COG Phase I pediatric oncology program here at our Doernbecher Children's Hospital, and with the leadership opportunity of building a de novo Pediatric Cancer Biology Program at OHSU, there's tremendous potential to build a focused team of laboratories that share a common goal of doing the best research and moving making results relevant to patients in the here and now.

Where there is a will, there is a way. Change can be tangible. And we are accountable.

Charles Keller, MD
keller@ohsu.edu

OSU College of Veterinary Medicine

2010-08-11T15:44:00.002-07:00

We thank Dr. Bernard Seguin (oncological surgery) and Dr. Shay Bracha (oncology) for meeting with us today to discuss the intersection of childhood and companion pet clinical trials for cancer. The specialized facilities at the Oregon State University College of Veterinary Medicine are truly outstanding, and represent a strong resource for partnerships in developing new treatments for soft tissue and bone sarcomas of childhood and adolescence.

[ above right: Jinu, Bernard, Charles & Elaine at OSU ]
[ note: neither Ducks or Beavers were harmed in the pursuit of this collaboration ]

The “Creating Hope Act of 2010” S.3697

2010-08-10T13:30:00.001-07:00

This important proposed bipartisan legislature by Senators Sam Brownback (R-KS), Sherrod Brown (D-OH), and Al Franken (D-MN) would encourage pharmaceutical companies to develop new drugs for rare childhood diseases, including cancer. Essentially, the pharmaceutical companies would receive a voucher to expedite FDA approval.

For more details, visit Nancy Goodman's website for KIDS V CANCER.

Suresh's Cover!

2010-08-09T23:21:00.001-07:00

Congratulations to Suresh whose multi-modal molecular imaging is the cover of Molecular Cancer Therapeutics ! The broader description of this study is that we can now investigate rhabdomyosarcoma tumor cell interactions with the blood vessels and the immune system... using optical imaging, and without the interference of, well, hair!

Many congratulations again to co-first authors Bev and Marcia, as well as Suresh!

[ For the abstract, click here ]

Jackson's Ride the Gorge

2010-08-09T16:42:00.000-07:00

This past weekend we had the good fortune to participate in Jackson's Ride the Gorge in Hood River, OR. This fundraiser honors the memory of 12 year-old Jackson Hill who battled osteosarcoma and inspired the beautiful ride through the Columbia Gorge. The money raised is used for increasing awareness and supporting research for sarcoma, a cancer of the connective tissue. We found ourselves humbled by the number of people who rode (300!) or volunteered (over 70!) to make this event happen and were delighted to have the opportunity to provide aide at rest stops and at the finish line alongside them.

It is safe to say that we have been moved by the enthusiasm and dedication of all involved and intend to participate (we hope as riders!) in the years to come.

(photos and text by Elaine, who with Audra volunteered at The Dalles support station)

Hyundai Hope on Wheels Award to Doernbecher & the PCB Program

2010-08-05T09:51:00.007-07:00

Our research team in the Pediatric Cancer Biology Program is grateful for this opportunity to further childhood cancer research on behalf of Hope on Wheels, Hyundai and their dedicated employees. The effect of Hope on Wheels can be tangibly seen across the nation, not only through the distinctive handprint cars, but through the innovative research that has been sponsored at so many academic hospitals and centers.

We are honored to have this chance to do our part.

for the KATU TV story, click here .

Congratulations to Sachiko!

2010-08-02T20:40:00.004-07:00

We are excited that Sachiko's cell and biochemical studies for IGF receptor inhibition in medulloblastoma have been accepted to Biochemical and Biophysical Research Communications. Co-authors include Tohru and Laura. A key aspect of this study is the use of primary cell cultures maintained under neural stem cell conditions. In general, our lab and others are trending away from the use of traditional cell cultures for medulloblastoma, especially when sonic hedgehog signaling might be important.

Again - many congratulations, Sachiko!

[ Aug 10, 2010: the manuscript is now available online here. ]

News feature on Jackson's Ride the Gorge

2010-07-29T23:16:00.001-07:00

We were honored to participate in a news piece tonight by Deb Knapp at KATU in Portland about a sarcoma fundraiser, Jackson's Ride the Gorge. This event is conducted by the NW Sarcoma Foundation this year and past years in memory of Jackson, a young man who lost his battle with osteosarcoma. For the online video link, see http://www.katu.com/home/video/99592974.html .

To register for the Ride, click here.

Scientific Presentations in Scottsdale and Princeton

2010-07-23T19:04:00.005-07:00

It was an exciting week for the Keller laboratory, with three presentation; 1 on rhabdomyosarcoma (Charles) & 1on satellite cells (Tohru) at the FASEB Muscle Satellite and Stem Cell Conference in Carefree (Scottsdale), Arizona, and 1 on rhabdomyosarcoma (Charles) at the Molecular Therapeutics Cancer Research Association Conference at Princeton University. All three presentations were received well, and what we hope is that more muscle stem cell biologists, and more pharmaceutical industry scientists, will become interested in rhabdomyosarcoma biology and therapy. In there, somewhere, was a red-eye flight, but it was certainly worth the extra effort.


[ above right: FASEB meeting with Michael Kyba (Univ of Minnesota), Charles and Andrew Brack (MGH/Harvard) ]
[ below right: CMTRA meeting at Princeton University ]

Tohru's FASEB Muscle Stem Cell Talk

2010-07-01T23:43:00.000-07:00

Congratulation to Tohru whose work in our lab on "The Role of Rb in Skeletal Muscle Stem Cell Pool Homeostasis" has been selected as platform talk for the upcoming FASEB Muscle Satellite and Stem Cell Conference in Carefree, Arizona.

Welcoming Jen

2010-06-25T09:10:00.000-07:00

We would like to welcome Jennifer Alabran as an important staff scientist and lab manager for the Keller lab at OHSU. Jen received a B.Sc. in Biology from Allegheny College, then went to the National Cancer Institute as a Cancer Research Training Award Fellow in the laboratory of Dr. John Letterio. When Dr. Letterio's laboratory moved to Case Western Reserve University, Jen enrolled in graduate school and received a M.Sc. in Pathology and Cancer Biology. From these studies, Jen is first author of the report of a synthetic trierpenoid therapeutic for neuroblastoma. Most recently Jen has been developing a preclinical cancer model in the T cell biology laboratory of Dr. Mark Jutila. Jen has a strong commitment to children with cancer in and out of the laboratory, and volunteers annually at camp for children with cancer in Montana.

Welcoming Monika!

2010-06-25T08:00:00.000-07:00

Dr Monika Davare will be joining our laboratory on September 1 as a staff scientist and as our pediatric brain tumor research projects leader. Monika has strong research portfolio, to be sure. In the Keller laboratory, she will lead our team investigating factors responsible for medulloblastoma progression and leptomeningeal metastasis. We look forward to having Monika as a member of our team!

" I received my PhD from the Molecular and Cellular Pharmacology Program at the University of Wisconsin – Madison. While in Madison, in Johannes Hell’s laboratory, I identified novel signaling complexes associated with CaV1.2 voltage gated calcium channel and demonstrated spatio-temporal regulation of the channel via associated adrenergic signaling complex. We published these data in the Journal of Biological Chemistry and in Science. In our PNAS paper we show the molecular mechanism for calcium channel upregulation that likely contributes to the calcium dysregulation in aging neurons correlated to age related neurodegeneration.

As a postdoctoral fellow with Dr. Thomas Soderling (at the Vollum Institute, OHSU), I have characterized the novel signaling complexes associated with calcium/calmodulin regulated kinases, including CaMKK and CaMK1g and identified the role of these kinases during neuronal development, including axonogenesis, activity regulated dendrite/spine formation as well as synaptic plasticity. These data were published as primary and secondary author papers in Journal of Neuroscience, Journal of Biological Chemistry, PNAS and Molecular and Cellular Neuroscience. With my extensive background in neuronal signal transduction, I am now highly motivated to focus research efforts on understanding the histogenesis and dissemination of brain tumors, particularly medulloblastoma and glioma.

As such with the Knight Cancer Foundation’s Career Development Award, I am exploring the role of calcium kinase signaling during medulloblastoma migration. In the coming year, I hope to intensify and focus these efforts, casting a wider net for putative therapeutic targets in Charles Keller’s laboratory. "

Introducing Liz

2010-06-25T07:35:00.000-07:00

As our laboratory transition from Texas to Portland, we'd like to acknowledge one of the key people who are helping make the process a success. Elizabeth 'Liz' Perkins is the Administrative Coordinator for the Pediatric Cancer Biology Program and other laboratories within the Pape' Family Pediatric Research Institute. Liz has extensive professional experience in enterprise-level organizations, as well as volunteerism, special events planning and entrepreneurship. Liz's experience in managing and organizing executive (board) level activities gives her a special insight into what makes a process successful, as well as how to avoid common pitfalls. We are grateful that Liz is a part of our team and look forward to growing a highly productive program with her as our founding team member.

Welcoming Elaine

2010-06-25T05:03:00.000-07:00

We are excited to welcome Elaine Huang as operational manager of the Pediatric Preclinical Testing Initiative at OHSU. Elaine hails from Baton Rouge, Louisiana, and received her B.S. in Microbiology from the University of Michigan. Elaine then attended graduate school at the University of Pennsylvania where she earned a M.Sc. in Immunology under Dr. Christopher Hunter studying host responses to T. gondii. Elaine's professional experiences include working in an industry-sponsored GLP/GMP clinical cell and vaccine production facility at U Penn. Most recently Elaine was a research associate at the Transgenic Mouse Model Shared Resource at OHSU, generating diverse genetically modified mouse models for the researchers using a full spectrum of reproductive technologies. In her off hours Elaine spends 'too much time' reading and knitting, that is when she’s not running around the various 'woodsy' parts of Oregon. Elaine will work in concert with Dr. Jinu Abraham, scientific manager of the PPTI, to discover and develop novel new treatments for childhood cancers. Welcome, Elaine!

Welcoming Audra

2010-06-24T22:28:00.001-07:00

Our laboratory welcomes Audra Lee to our team of basic and translational scientists in the Keller lab at OHSU. Audra earned both B.S. and M.S. degrees in Biology from Ball State University before becoming an important contributing scientist to the laboratory of Dr. Robert Wechsler-Reya, a colleague and one of the rising stars in childhood medulloblastoma research. In Rob's lab, Audra was first author on an important study on postnatal neural stem cells of the cerebellum published in Nature Neuroscience. Audra also has vital experience in the biotechnology field having worked at Zen Bio, Inc, in Research Triangle Park, NC. In her free time, Audra is an aspiring author and enjoys exploring the outdoors.
In our laboratory, Audra will work to further develop an exciting in ovo system for discovering drugs that inhibit metastasis which has been developed thus far by means of an Innovation Grant the Alex's Lemonade Stand Foundation.

Welcome, Audra!

Welcoming Summer Student, Lauren Peterson

2010-06-24T22:14:00.000-07:00

It is our pleasure to welcome Lauren to the lab team. Lauren will be researching and writing a manuscript on an important aspect of pediatric clinical research. This is a project for which her undergraduate studies and her social advocacy roles makes her especially qualified:

"I’ve grown up in eastern Washington and am attending Walla Walla University as a Humanities major with a Chemistry minor. I enjoy working with kids, whether it’s teaching swimming lessons or being a camp counselor. As well as working with kids, I enjoy writing and editing, which is why I am very excited to work on this writing project with Dr. Keller this summer. -- Lauren "

Welcoming Ken

2010-06-24T14:00:00.000-07:00

We are pleased to welcome physician-scientist Dr. Ken Kikuchi as a postdoctoral fellow to our laboratory starting July 1. Ken Received his MD and PhD degrees from Kyoto Prefectural University of Medicine in 1999 and 2008, respectively. For his PhD, Ken studied under Dr. Hajime Hosoi. The results of Ken's studies on the effects of the Pax3:Fkhr oncogene on alveolar rhabdomyosarcoma are published in the Biochemical and Biophysical Research Communications. Ken's long term career goal is to be the principal investigator of an independent academic research laboratory studying rhabdomyosarcoma biology. Welcome, Ken!

You Can Participate in our Novel Therapeutics Studies !

2010-06-23T10:45:00.000-07:00

One would like to think that tangibly better treatments for rhabdomyosarcoma, medulloblastoma and other childhood cancers can be found in a matter of years, instead of tens of years. Finding new treatments starts with research, perhaps even a new research approach to identifying effective new treatments. The Pediatric Preclinical Testing Initiative (at the Pediatric Cancer Biology Program, Pape' Family Pediatric Research Institute, Oregon Health & Science University) focuses on finding molecules in childhood cancers that can be directly turned off or on by drugs so that the tumor stops growing. Behind our novel approach is the use of genetically-engineered mice. Our Pediatric Preclinical Testing Initiative uses mice modified from before birth so that at a certain age, and in a certain tissue, the same mutations found in a child’s cancer are activated in the mouse. These special mouse models of childhood cancer can be used to test a treatment to see whether the tumor growth and spread (metastasis) can be reversed. The specific aspect of these mice having normal immune systems is a real plus, too, because white blood cells play an important role in how tumors evolve and respond to therapy.

Our program is designed around community participation. Through the Doernbecher Children's Hospital Foundation at OHSU, you can contribute directly to this grass-roots initiative. Donations through small gifts or grants will assist in studying compounds that may be effective in treating such childhood cancers as alveolar rhabdomyosarcoma, embryonal rhabdomyosarcoma, or medulloblastoma (the alveolar rhabdomyosarcoma model was featured by Dr. Keller's long time collaborator and former mentor, 2007 Nobel laureate Mario Capecchi, in his Nobel Prize lecture.) For example, a grant of $8500 enabled the PPTI to study a promising multi-kinase inhibitor in mice with alveolar rhabdomyosarcoma.

For additional information regarding supporting this program please contact Ms. Sue Nicol, Doernbecher Children's Hospital Foundation, at nicols(at)ohsu.edu . For additional information on this program, please contact PPTI leader Dr. Charles Keller at keller@ohsu.edu. Results obtained through these studies will be shared with the National Cancer Institute’s Cancer Therapy Evaluation Program, as well as the Children’s Oncology Group, which designs clinical trials for childhood cancer.

Acknowledging the Amazing Team at GCCRI

2010-06-20T14:35:00.005-07:00

As our laboratory moves officially from San Antonio to OHSU in Portland next week, it's important to acknowledge the incredibly talented group we've been able to work with at GCCRI in San Antonio.

In the time since our lab started in 2005, we've published over 2 dozen papers with funding in the form of R01(s), NIH S10 grants and other competitive awards. All this was possible through the hard work and intellectual contributions of postdoctoral fellows including:

- Eri Taniguchi (who went on to a second fellowship at MGH/Harvard and is now at Cincinnati Children's Hospital),
- Koichi Nishijo (who is now Clinical Leader in Oncology Therapeutic Development, Bayer Japan),
- Sachiko Ohshima (who has gone on to a second fellowship with Dr. Marina Emborg, Univ. of Wisconsin, Madison),
- Tohru Hosoyama (who has gone on to a second fellowship with Dr. Masatoshi Suzuki, Univ. of Wisconsin, Madison),
- Min Jung Cho (who is now faculty in the Dept of Pediatrics, Busan National University Hospital, Korea),
- Anu Soundararajan (who has gone on to a second fellowship with Dr. Peter Fox at Research Imaging Institute, UTHSCSA),
- Aoife Kilcoyne (who is a Radiology Resident in Dublin, Ireland), and
- Jinu Abraham (who will be taking an important leadership role with the PPTI in our lab at OHSU).

We've also had the good fortune to have diligent, kind-hearted and highly effective scientific staff, including the tireless Laura Nelon, Xiaolan Yi, Beverly Schaffer and Sheila Hampton. Laura, Xiaolan and Sheila made the move possible, and I personally can't thank them enough. In fact, there are almost no words that can adequately express our appreciation. The single most productive person, at least by authorship count, would be Suresh Prajapati, who managed our Small Animal Imaging Resource Facility with incredible efficiency and professionalism.

We graduated four graduate students, Patrick "P.J." Hawkes, Lisa Nevell, Corrine Chua, and the award-winning Aislynn Samano. Aislynn was particularly resilient in finding a way to rate therapies for medulloblastoma using our mouse models. And of course, Lisa is now a postdoctoral fellow with Nobel laureate, Mario Capecchi. We've had many other part time and Summer students in our lab that we've highlighted previously (including Mandy McCleish, Jerry Chang, Hunter Weibush, Steven McCarthy and Andrea Rodriguez), but it's important to acknowledge the incredible Courtney Kubicek, a nursing student who began each schoolday at 6am by examinations... of our mice! She will surely be an outstanding nurse anesthetist one day soon. Medical student Imran Aslam deserves special recognition, too, for working with Tohru to turn an AMA medical student seed grant into an important part of an R01 application that scored 25 (7th percentile).

The staff at GCCRI deserve our deep thanks, also. They include our fearless and sage Administrator, Bill Chessher (as a former hospital administrator, rodeo man, heavy equipment operator and poultry farmer, Bill's memoirs should be rather interesting), financial and information technology head Tony Mendicino (who knew both could be done by the same person, and so effectively!), Danette Besancon (the ultimate can-do person), Richard McDougle (to whom all PI's must account), the talented graphics artist David Rodriguez, helpful grantsperson Lucy Hernandez, talented histologist Michelle Brady, flow cytometry aficionado Jenny Rebeles, the gifted network systems engineer Barron Blackman, the sleepless network support person Tony Dennie, as well as the undeniable and very loved facility manager Tracy Byrd and Irma Gonzalez, who we couldn't have done without!  Our heart goes out to Frances 'Fran' Melton, who performed the impossible with our Oncomouse-related MTA's, and colleague Chris Burke, who managed our busy and complex IP portfolio without ever losing her sense of humor. Gaye, Joe, Richard and Teresa in Purchasing are deeply valued also.

What can be said of our fearless founding leader, Dr. Sharon Murphy? Although she's at the Institute of Medicine now, her insights into team building and driving biological problems cannot be surpassed, and we appreciate the opportunity to continue learning from her wisdom. Our work, too, couldn't have been accomplished without the support of Debbie Morrill and Kim Warshauer. Leslea Sarro and Tammy Linn in lab animal resources literally kept our lab's heart beating.

Finally, we'd like to thank the Foundations that have supported our work, including the Scott Carter Foundation, Alex's Lemonade Stand Foundation, the National Brain Tumor Society, the Sarcoma Foundation of America, the Amschwand Sarcoma Cancer Foundation, the Rally Foundation and the Joanna McAfee Childhood Cancer Foundation. Their support has allowed us to create the Pediatric Preclinical Testing Initiative and to pursue high risk, high reward projects that have gone on to successful R01's.

Charles & Team

Rhabdomyosarcoma Paper accepted to MCT

2010-06-14T12:21:00.003-07:00

Congratulations to co-first authors, Bev Schaffer (Keller lab) and Marcia Grayson (Infante lab) whose manuscript, "Immune Competency of a Hairless Strain for Improved Preclinical Studies in Genetically-Engineered Mice" was accepted today to Molecular Cancer Therapeutics, an AACR Journal. This study describes a way to improve genetically-engineered mouse models of cancer (particularly rhabdomyosarcoma) by making them fur-free. Other co-authors include Keller lab current and past members, Laura Nelon, Suresh Prajapati, Joy Wortham, Courtney Kubicek, Mandy McCleish, Michelle Brady and Tohru Hosoyama, as well as collaborators Tony Infante (UTHSCSA Pediatrics & Immunology), Inkyung Jung and Joel Michalek (UTHSCSA Biostatistics), Leslea Sarro and Marti Hanes (UTHSCSA Lab Animal Resources), Brian Rubin (Cleveland Clinic) and Charlie Clifford (Charles River Laboratories).

[ Update! 7/23/10... exciting news, this paper will be featured as the Cover Article ]

R01 grant receives great score (now hiring!)

2010-06-13T06:08:00.001-07:00

We are excited that our multiple-PI NIH R01 research grant in collaboration with Dr. Denis Guttridge at OSU has received a very favorable priority score, putting it in the top 7% of grants being reviewed this past cycle. This grant application addresses the role of NFkB in the childhood muscle cancer. The preliminary data for this application would not have been possible without the hard work and intellectual contributions of Keller lab postdoctoral fellows, Drs. Sachiko Ohshima and Tohru Hosoyama, as well as key experiments designed and implemented by medical student M. Imran Aslam, who was funded by an AMA Medical Student Research Seed Grant.

Naturally, of course, we will be looking for an additional postdoctoral fellow for this project. Please see our ad in Naturejobs, which is also below:

Postdoctoral Research Fellowship for Signaling in Muscle Stem Cells and Rhabdomyosarcoma. This mentored position in the Keller laboratory will empower the candidate to create and analyze complex conditional genetic mouse models of pediatric cancers for the purpose of developing novel molecular therapies. The primary goal for this position is to investigate the role of growth factor and cytokine signaling in the childhood muscle cancer, alveolar rhabdomyosarcoma.

Qualifications Required: MD and/or PhD, preferably with 3-4 years experience in Biochemistry; molecular biology; animal models and animal surgery; small animal imaging; cancer biology.

How to Apply: Please send cover letter and CV with 3 references to Dr. Charles Keller, at keller@ohsu.edu

Implications for Wilm's Tumor

2010-06-12T21:59:00.001-07:00

An interesting article in Stem Cell Research by Lusis et al this week discusses the embryonic and fetal stem cells that become the kidney, and how to culture and study this type of cell. This report has some rather important implications for Wilm's Tumor, a embryonic form of kidney tumor in children. For additional detail, follow the link to the original article or see our Commentary.

We are thankful to the Scott Carter Foundation for their support through a Scott Carter fellowship to Jinu Abraham, lead author of this editorial.

Suresh's Medulloblastoma Study Accepted for Publication

2010-05-30T09:07:00.001-07:00

Congratulations to Suresh whose study, "Micro-CT Based Virtual Histology Evaluation of Preclinical Medulloblastoma," has been accepted for publication in the journal, Molecular Imaging and Biology, the official journal of the Society of Molecular Imaging. Special thanks to co-author, Dr. Aoife Kilcoyne, a lab alumnist and now a Radiology resident in Ireland.

Postdoctoral Positions Available

2010-05-04T19:00:00.001-07:00

Our laboratory has 2 openings for postdoctoral fellows beginning July 1, 2010. These mentored positions will empower the candidates to create and analyze complex conditional genetic mouse models of pediatric cancers for the purpose of developing novel molecular therapies. The primary goals for these projects are to understand the role of proteins in the metastatic progression of the childhood brain tumor, medulloblastoma, or the childhood muscle cancer, rhabdomyosarcoma. Employing molecular biology, biochemistry and small animal imaging, the candidate will have the opportunity to identify critical factors in tumor maintenance and tumor progression from which new therapies can be developed. Rapid translation to the clinic is the underlying goal.

Interested candidates should email a cv to Charles at keller@ohsu.edu .

.

Macy Easom Golf Tournament benefits Childhood Cancer Families

2010-04-11T19:08:00.002-07:00

Yesterday, Middle Georgia Orthopaedic Surgery and Sports Medicine sponsored the 4th annual Macy Easom Memorial Charity Golf Tournament, benefitting the Joanna McAfee Childhood Cancer Foundation. Macy was a young girl who, like Joanna, lost her battle against childhood cancer. Macy's parents and Joanna's parents (along with help from JMCCF and MGO employees and volunteers) organize this annual benefit to raise awareness and to provide tangible support to families of children currently going through their own treatment. It was a privilege to be a part of this event near Warner Robins, GA (where the JMCCF is headquartered). This fundraiser is a heart-warming way in which the memory of Macy, Joanna and other children from this area can be honored by helping the families of children who are currently facing the same challenges.

[ below: Charles with golf partners (left to right) Jeff, Aaron and Sam. ]

Tohru's Paper accepted to Genes & Cancer

2010-04-06T09:00:00.006-07:00

Congratulations to Tohru, whose paper on pituitary tumors was just accepted to Genes & Cancer. Tohru showed that a certain protein (ie, homeobox transcription factor) defines a newly discovered type of progenitor cells after birth that give rise to pituitary tumors. (yes, actually, this was a fortuitous discovery... as we were originally trying to investigate childhood muscle and cerebellar tumors). Tohru's work fits well with the recent important discovery of pituitary stem cells by Gleiberman and colleagues. The publication of our work in Genes & Cancer is particularly appropriate because of this journal's focus on the interplay of development and cancer biology. Our thanks to UTHSCSA and extramural collaborators, who include pathologist Brian Rubin at the Cleveland Clinic, Bernd Scheithauer of the Mayo Clinic, and Wilmon Grant and Daniel Marks at OHSU.

[ above right: histology from a new pituitary tumor mouse model;

below right: microCT-based Virtual Histology of a pituitary tumor. ]

[ update June 6, 2010: Tohru's paper is now in print, Genes Cancer 2010;1 388-402 ]

Our Laboratory is Moving to OHSU, Portland !

2010-03-31T17:00:00.003-07:00

I'm excited to announce that our laboratory is moving to the Oregon Health & Science University where my team and I will be building and leading a Pediatric Cancer Biology program as well as a robust Preclinical Testing Program for childhood cancers. Whether to move a laboratory requires careful consideration, as described by Joe Simone in his 'Maxims'. Some key aspects in pursuing this opportunity for our lab are:

- an existing COG Pediatric Oncology Phase I program, so that we can more easily move new treatments from the laboratory bench to the clinic,

- Strong leadership in the Department of Pediatrics by Chairman and pediatric oncologist, Dr. Stacy Nicholson,

- Clinical trials expertise including Pediatric Hematology Oncology division chief, Dr. Linda Stork, and Phase I program PI, Dr. Suman Malempati (who currently conducts a COG clinical trial of an Igfr-1 inhibitor for rhabdomyosarcoma),

- An exceptional stem cell biology community with the Oregon Stem Cell Center to complement our interest in muscle and tumor stem cells,

- Field-leading expertise in gene therapy, including the research of Pape' Family Pediatric Research Institute Director, Dr. Markus Grompe, and fellow pediatric oncologist faculty member, Peter Kurre,

- A tradition of excellence in Neuroscience, complementing our interests in medulloblastoma, through the Vollum Institute led by Dr. Richard Goodman,

- a strong Division of Biomedical Engineering to enhance our multi-disciplinary approach to cancer research,

- opportunity to partner with the community in growing the pediatric cancer biology program faculty through collaboration with The Doernbecher Children's Hospital Foundation,

and importantly,

- the opportunity to collaborate with 2009 Lasker-Debakey Prize awardee, Dr. Brian Druker. Brian and colleagues pioneered the use of Imatinib (Gleevec, or STI571) as a targeted molecular therapeutic for Chronic Myelogenous Leukemia (CML). This precedent of finding a non-chemotherapy treatment for CML is one that we would very much like to repeat for childhood cancers. Such an approach would make a lot of sense, because growth factor receptors known to be active in many childhood cancers belong to the classes of kinases for which many new drugs are being developed for adult cancer. We have already had very productive collaborations with our colleagues Drs. Jason Glover, Jeff Tyner and Mark Loriaux in the Druker laboratory that will lead to co-authored studies this Spring.

We look forward to being a part of the OHSU community, and forging new ground in the discovery of novel and more effective treatments for childhood cancer.

Charles

"Start by doing what is necessary, then do what is possible, and suddenly you are doing the impossible", St. Francis of Assisi

[ above right: Mt Hood and Downtown Portland. photo credit, USGS ]

Spring COG meeting in Los Angeles

2010-03-26T17:00:00.020-07:00

The Children's Oncology Group Spring 2010 meeting was held in Los Angeles March 24 - 26, with our participation being in the Soft Tissue Sarcoma, Preclinical Testing and CNS (brain tumor) sessions. Research by Jinu and Anu was very well received at the Tuesday sarcoma session in Charles' presentation of, "Preclinical Rhabdomyosarcoma Studies in Genetically-Engineered Mice". These meetings are fabulous for establishing new treatment paradigms that bridge basic science and clinical trials.

Molecularly targeted therapies are generating a lot of excitement.

It pays to have a sense of humor

2010-03-12T11:54:00.000-08:00

Recently Laura went to a conference for mouse colony management and came back with some souvenirs. Oddly, they seem to have a life of their own. It's certainly nice to have light moments every once in a while.