The Keller Laboratory at cc-TDI: an informal word on the research in the Keller Laboratory

Saturday, February 28, 2009

an informal word on the research in the Keller Laboratory

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, an orthopedic oncologist 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 25¢ fertilized chicken 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 starting 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 our novel mice.

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 my postdoctoral fellow, Koichi Nishijo. 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 3 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 we did present our results at a Children’s Oncology Group symposium a few weeks ago to help select a non-chemotherapy drug to add to the next COG trial for rhabdomyosarcoma).

We’re fortunate that despite the economic downturns that we’re doing pretty well so far… R01 funding from the National Cancer Institute, grants from the ALSF, the St Baldrick’s Foundation, the National Brain Tumor Society, the Joanna McAfee Foundation and more. Seven publications in print or accepted in 2008. This are truly exciting times. On top of all this is our mouse drug testing program mentioned above, which is open to public participation (for more details, see the left column of our blog). And just to put a plug in for a colleague’s new lab, try visiting Dr. David Langenau’s website . David has made a zebrafish model of embryonal rhabdomyosarcoma. He treats these little fish with drugs, right in the tank water. Also see Dr. Rene Galindo's website on using fruitflies to understand rhabdomyosarcoma. It will probably take a lot of new approaches and cooperation between groups to make the big impact we’re all hoping for, but it can be done.

Where there is a will, there is a way. Change can be tangible.

Charles Keller, MD
~~kellerc2@uthscsa.edu~~ keller@ohsu.edu

[ many thanks to collaborator Dr. Bryan W. Jones who took this picture on a hike in Utah. ]

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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 Children's Cancer Therapy Development Institute 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 Children's Cancer Therapy Development Institute, 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 {see 16 minutes onward}.)

For additional information regarding supporting this program please contact Charles Keller at charles@cc-tdi.org. 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.