Gastrointestinal Oncology SPORE
Juanita Merchant, M.D., Ph.D.
Translational research in gastrointestinal cancer is critically needed to enhance applications of the knowledge gained through the rapid expansion of our understanding of the genetic and molecular basis of the pathogenesis of cancer. A comprehensive faculty career development program is proposed to meet the urgent need for increased number of clinicians and basic scientists devoted to gastrointestinal cancer research. Although some of this need has been addressed through NIH T32 training grants for post-doctoral fellows, transition to an independent, funded research career in gastrointestinal cancer for full time faculty has been difficult. Direct funding of young investigators with outstanding new translational research programs relevant to gastrointestinal cancer is proposed to address this limitation. Focus on young faculty members will ensure attraction of new, energetic investigators, who when successful, will likely maintain a long-term research interest in gastrointestinal oncology. A rigorous selection process is outlined that includes University-wide recruitment, strong emphasis on recruitment of women and minorities and comprehensive basic and clinical science mentoring. Close evaluation and monitoring is achieved through monthly meetings and annual internal and external review for continued funding. In addition to tailored scientific mentorship of individual projects, the GI SPORE career development program establishes an educational process for young investigators that is closely integrated with existing programs within the Cancer Center, Medical School, and the Michigan Institute for Clinical and Health Research. A major emphasis is placed on salary support for clinician scientists to ensure adequate time commitment to their SPORE research program.
Career Development Program Pilots
Hepatocellular Carcinoma Stem Cells and Microenvironmental Influence of Immune Cell Subsets
Targeting CDC25 phosphatases in gastrointestinal cancers
Targeting Tumor Specific Outlier Kinases through Kinome Profiling of Pancreatic Cancers - A Pilot Study for Personalized Treatment of Primary Human Tumors XenograftsPrinciple Investigator:
Chandan Kumar, Research Assistant Professor
Department of Pathology
Arul M. Chinnaiyan, M.D., Ph.D., Professor Department of Pathology
Diane M. Simeone, M.D., Professor Department of Surgery
11/1/2011 - 10/31/2012
Evan as next generation high throughput sequencing techniques are beginning to deliver on the promise of providing a comprehensive landscape of molecular aberrations present in individual tumors, the ensuing challenge is to translate this information into clinical practice. The questions of driver versus passenger aberrations, clonal heterogeneity of tumors, role of stoma in tumora sustenance coding RNAs in disease and therapy are all expected to be unraveled in the coming days leading to profoundly novel insights, improved diagnostics and therapeutic approaches. Here, we are addressing a more immediate practical question: based on all that we already know, based on all the molecular targets that are already characterized and for which effective inhibitors are already in use (or undergoing clinical trials/ advanced preclinical evaluations), can we use the currently emergent molecular information from deep sequencing of tumors, to impact treatment and patient survival.
Hepatocellular Carcinoma Stem Cells and Microenvironmental Influence of Immune Cell SubsetsPrinciple Investigator:
Theodore Welling, M.D., Assistant Professor
Department of Surgery
11/1/2010 - 10/31/2012
In this study Dr. Welling proposed studies exploring the interactions between hepatocellular carcinoma (HCC) cancer stem cells and their microenvironment, with an emphasis on the immune response in the tumor microenvironment.
Targeting CDC25 phosphatases in gastrointestinal cancersPrincipal Investigator:
Tomasz Cierpicki, Ph.D., Assistant Professor
Department of Pathology
11/1/2010 - 10/31/2012
The goal of Dr. Cierpicki's proposal is to identify and characterize small molecule inhibitors that disrupt CDC25B-CDKs/Cyclin binding as potential anticancer agents. By activation CDKs through removal of inhibitory phosphorylation, CDC25 family members play an essential role to ensure cell cycle progression. Dr. Cierpicki's lab has developed an NMR-guided approach to identify CDC25 inhibitors that disrupt the binding between CDC25 and CDKs/Cyclin and have identified a small molecule compound, 8H8 that binds to CDC25B.