You Can Participate in our Novel Therapeutics Studies !

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

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

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!)

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

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

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

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 .

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