David Reiner

Education and Training

• Carleton College, BA, 1988
• University of Washington, PhD, Genetics, 1996
• University of Washington, Postdoctoral Training, 1997
• University of California, Berkeley, Postdoctoral Training
• University of North Carolina at Chapel Hill , Postdoctoral Training

Research Interests

• A long-term goal of the Reiner lab is to understand the molecular basis underlying the contribution of signal transduction to development. What determines the extraordinarily high fidelity of developmental systems – and how novel signaling mechanisms and components contribute to that fidelity – remains a fundamental gap in the field. The skeleton of most core signaling cascades has been defined by the convergence of complementary research using model genetic organisms, mechanistic analyses in mammalian cell culture, biochemical and biophysical studies, and pathophysiological definitions of important players. We even know many so-called “modulator” genes to flesh out the signaling world. Yet how these components are woven into dynamic and plastic signaling networks during development is still not well understood. Our research bootstraps from the Ras small GTPase, the most mutated mammalian oncoprotein. Among the relatives of Ras, we look downstream of Ras (Ral), in the shadow of Ras (Rap1), and at a cousin of Ras in metabolism and development (Rheb), which also connects back to Ral. We have also found novel signals downstream of Ral, a missing link in Ras-dependent tumors. Most of our work uses the genetic model organism, C. elegans, though we have published cross-platform studies by letting the worm lead the way to insights into mammalian biology. Another focus of the Reiner lab is to harness the power of C. elegans genetics to engineer animals for highly sensitized drug discovery screens. Here in the IBT Center for Translational Cancer Research on the 9th floor of the Alkek building is the John S. Dunn High Throughput Screening Core Facility, part of the Gulf Coast Consortia for Quantitative Biomedical Sciences. Also our neighbor on the 9th floor is the Center for Advanced Imaging, which contains state of the art confocal imaging as well as high throughput imaging instruments, and the expertise to use them. With them we are working to define a novel cross-platform drug discovery pipeline, with model organism small molecule inhibitor identification generating candidates for cell culture and mouse validation, and from there into the clinic. Consequently, our efforts are inherently collaborative. A key element of our project design is that, unlike conventional targeted drug therapy paradigms, we do not assume that we know the best target in a given system. Rather, we sensitize a system with a known mutation as an entry point for high throughput small molecule screening for specific phenotypic endpoints. We reason that the target identification can come later; we are looking for potentially valuable inhibitors in a given system regardless of the target, thereby complementing existing drug discovery paradigms. We began with oncogenic Rac and Ras as proofs of principle, and will extend to other entry points. We emphasize that in the long term our drug discovery scheme is generalizable: to other diseases with highly conserved molecular entry points (channelopathies, neurodegeneration, dystrophies, etc., as well as oncogenes) and to other model system platforms (yeast, worms, flies, frogs and fish).