An assistant professor at the Greehey Children’s Cancer Research Institute (GCCRI), aims to improve therapies for specific types of childhood cancer. Dr. Keller is a board-certified pediatric oncologist specializing in the development of more effective, less toxic therapies for a type of childhood muscle cancer called rhabdomyosarcoma, and a type of childhood brain tumor called medulloblastoma. To achieve these goals, Dr. Keller’s laboratory utilizes physiologically-accurate mouse models of three related pediatric small round blue cell tumors: alveolar rhabdomyosarcoma, embryonal rhabdomyosarcoma and medulloblastoma.   
       

    Dr. Keller joined the Greehey Children's Cancer Research Institute in January of 2005 as a Principal Investigator in Developmental Cancer Genetics and Therapeutics and as an Assistant Professor in the Department of Cellular & Structural Biology. Dr. Keller attended Tulane University where he received a degree in Biomedical Engineering prior to attending Baylor College of Medicine where he received his M.D. degree. After completing his internship and residency in Pediatrics at Texas Children's Hospital, Dr. Keller trained in Pediatric Hematology-Oncology at the University of Utah and as a postdoctoral fellow in the laboratory of 2007 Nobel laureate, Mario R. Capecchi.

 

     The diseases studied by Dr. Keller’s laboratory have evaded traditional research approaches for many years.  Alveolar and embryonal rhabdomyosarcoma are aggressive muscle cancers that are difficult to treat if not completely resected or if metastatic.  Interestingly, embryonal rhabdomyosarcomas have a markedly better potential for cure than alveolar rhabdomyosarcomas when matched for stage.  Understanding the fundamental biological differences between these related cancers is the motivation for studying alveolar and embryonal rhabdomyosarcomas in parallel.  Medulloblastoma is an aggressive childhood brain tumor of the cerebellum that, even when resected, requires treatment that can impair cognition, and when metastatic to the leptomeninges is very difficult to cure.  Medulloblastomas and embryonal rhabdomyosarcomas share a common pathway of Sonic Hedgehog/Patched1-mediated proliferation, which makes parallel therapeutic investigation of particular interest.

 

     In their new approaches, Dr. Keller’s team has developed and characterized pediatric preclinical cancer models that will shed light on several fundamental biological questions and many clinically relevant aspects of cancer therapeutics.  These models are being used test the hypothesis that misregulated developmental genes drive tumorigenesis at both early and late stages of disease. These models have also allowed their laboratory to explore the spatial and temporal origins of these tumors. This latter interest has led Dr. Keller to study the biology of muscle stem cells, called satellite cells.  However, the long-term emphasis of Dr. Keller’s laboratory’s research is the investigation of how primary and secondary genetic changes lead to tumor progression, since advanced disease remains the greatest challenge in the treatment of children with these cancers.  To this end, Dr. Keller’s laboratory will be the first to incorporate genetically-engineered models into the National Cancer Institute’s Pediatric Preclinical Testing Program, and Dr. Keller is also a recently appointed member of the Children’s Oncology Soft Tissue Sarcoma committee that designs clinical trials for rhabdomyosarcoma. 

 

     In addition to his laboratory’s cancer research, Dr. Keller is Director of the GCCRI Small Animal Imaging Facility, which conducts research into anatomical & molecular imaging methods for mouse models of human disease.