Bench to Bedside

We're excited to share that Charles has been appointed as a full time member of the Children's Oncology Group (COG) Soft Tissue Sarcoma Committee. This committee designs clinical and translational trials for rhabdomyosarcoma and other soft tissue sarcomas. This appointment follows other COG activities in recent years including ad hoc participation in the Soft Tissue Sarcoma Committee since 2001. Also, Charles has also been an awardee of the COG Young Investigator Award (2001) and a recipient of the COG Translational Research Award (2001-2002). The results of the latter are published as a COG report entitled, "Rhabdomyosarcomas utilize developmental, myogenic growth factors for disease advantage". This study was the foundation upon which our more recent from-the-bench-towards-bedside efforts have been focused. Our lab looks forward to being able to contribute more to clinical and translational trial design as new, molecularly-targeted drugs become available to pediatric patients.

Collaborator Andrew Brack visits GCCRI

Friend and collaborator, Dr. Andrew S. Brack, gave a terrific seminar presentation at GCCRI today. Andrew is an Assistant Professor at the Center for Regenerative Medicine at MGH, as well as a member of the Harvard Stem Cell Institute. A recent trainee of our other valued colleague, Dr. Thomas A. Rando at Stanford, Andrew has established a productive independent laboratory of his own and is a young rising star in the muscle biology field. As ever, the cross-pollination between muscle cancer biologists and muscle biologists leads to interesting conversations, novel ideas, and new outlooks on ways to treat muscle cancer. We are grateful to Andrew for making the trip to San Antonio and giving such a great seminar on satellite cell (muscle stem cell) renewal.

[ PICTURED: Andrew (left) with Koichi (right) at the Alamo ]

Koichi and Tohru's paper accepted to The FASEB Journal

Congratulation to Koichi and Tohru as first and second author on a muscle stem cell physiology / rhabdomyosarcoma study that was accepted today to The FASEB Journal. Other lab members who co-authored this work include Bev, Suresh and Mandy - as well as lab alumnist Ali Bahadur. We are grateful for the contributions of our collaborators, especially Chris Bjornson who is a member of the laboratory of Thomas Rando and our pathologist collaborator, Brian Rubin.  We are grateful, too, to the Scott Carter Foundation for sponsoring Koichi's fellowship.  

  
[ pictured on above right: a green myotube and its blue nucleus with an adjacent pink-white muscle stem cell (satellite cell). Pictured below, Koichi (left) and Tohru (right). ]

[ Koichi & Tohru's paper is now online. ]

Imran awarded AMA Seed Grant

Congratulations to Imran, who has been awarded a 2009 Medical Student Seed Grant from the American Medical Association Foundation. Imran's project will investigate the role of interleukin receptors in rhabdomyosarcoma biology and therapeutic strategies. This is a great start to Imran's project as a candidate for the M.D. with Distinction in Research Program at our medical school. We're very impressed with the trajectory of this future physician-scientist.

[ pictured at right: Imran hard at work in the lab following a set of medical school exams. ]

[ update 05/22/09: Imran has been accepted to the MD with Distinction program at UTHSCSA! Congratulations, Imran! ]

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. ]

GCCRI Symposium

In celebration of the 5th anniversary of the GCCRI we held a symposium on the Genetics and Biology of Childhood Cancer at the Hotel Contessa February 26 - 27th. Our founding director Dr. Sharon Murphy also attended (Sharon is now a Scholar-in-Residence at the Institute of Medicine). The Keller lab hosted the session on disease models and preclinical studies. Speakers in this session included Tom Look (DFCI) who gave a great talk on ALK that follows his Fall report in Nature, Rene Galindo spoke on drosophila models of alveolar rhabdomyosarcoma, Pat Reynolds talked about exciting new retinoid therapies for neuroblastoma and leukemia, and Peter Houghton reviewed the tremendous progress by the Pediatric Preclinical Testing Program. We can't thank the speakers enough for making this an exciting, interactive exchange.

In memory of Patsy McCleish

Our deepest sympathies go out to Mandy and her sisters following the passing yesterday of their mother, Patricia Mary McCleish. Patsy was a loving mother and guiding example of strength throughout her many years of recurrent, metastatic cancer. Her positive attitude and love of life were an example to everyone who met her. Patsy's services will be held 1pm on Saturday February 14th at St. Francis of Assisi Church, 4201 De Zavala Rd, San Antonio. There will be a small gathering of family and friends at Mandy's home following the services.

The family asks that in place of flowers that a donation be made in her honor to the American Cancer Society to benefit research for lung or liver cancer.

Our hearts go out to Mandy and her sisters, Nicole Quirk and Allison McCleish, in this saddening time.