The Ding Laboratory
Introduction:
The main research focus of
the Ding laboratory is to
develop and integrate chemical and functional
genomic tools to study stem cell biology and regeneration.
Recent advances in stem cell biology may make possible new approaches for the treatment of a number of diseases including cardiovascular disease, neurodegenerative disease, musculoskeletal disease, diabetes and cancer. These approaches could involve cell replacement therapy and/or drug treatment to stimulate the body’s own regenerative capabilities by promoting survival, migration/homing, proliferation, differentiation and reprogramming of endogenous stem/progenitor cells or more differentiated cells. However, such approaches will require identification of renewable cell sources of engraftable functional cells, an improved ability to manipulate their proliferation and differentiation, as well as a better understanding of the mechanisms that control their fate/function.
Equipped with high throughput screening platform and large arrayed chemical libraries, we have been constantly developing and integrating new chemical and functional genomic tools to study stem cell biology and regeneration. Our current works have focused on screening the chemical libraries to identify and further characterize small molecules that can control stem cell fate in various systems, including (i). Self-renewal regulation of embryonic and adult stem cells; (ii). Directed and step-wised differentiation of embryonic stem cells toward neuronal, cardiac and pancreatic lineages; (iii). Directed neuronal differentiation and subtype neuronal specification of human neural stem cells; (iv). Cellular plasticity and reprogramming of lineage-restricted somatic cells to more primitive precursor cells; (v). Functional proliferation of adult cardiomyocytes and pancreatic beta cells; (vi). Developmental signaling pathways (i.e. Wnt, Hh, BMP and FGF) and epigenetic mechanisms (histone and DNA de/methylation). (vii). Development of new technologies for stem cell derivation. Moreover, major efforts are devoted to characterize the molecular mechanism of these identified small molecules using various approaches, including detailed structure-activity-relationship (SAR) studies, affinity chromatography for target identification, transcriptome profiling, proteomics analysis, chemical/genetic epistasis, and biochemical and functional assays in vitro and in vivo. So far, functional small molecules and fundamental mechanisms have been identified and are being characterized in each of the above twenty plus distinct biological processes involving regulation of stem/progenitor cells. More recent examples include identification and characterization of distinct small molecules for hESC self-renewal and clonal expansion/survival; dopaminergic neuron specification from mESCs; derivation of rat pluripotent stem cells; reprogramming of somatic cells to pluripotent state (iPS cells) under chemically defined conditions; definitive endoderm and pancreatic induction; chemically defined monolayer conditions for self-renewal of ESCs and their directed differentiation to cardiac lineages; proliferation of human beta cells; and regulating Wnt signaling. Those studies may ultimately facilitate the therapeutic application of stem cells and the development of small molecule drugs to stimulate tissue and organ regeneration in vivo.
Sheng Ding did his undergraduate at California Institute of Technology with Drs. Grubbs, Rees, Goddard, Myers and Chan. His work with Dr. Grubbs (2005 Nobel Laureate in Chemistry) resulted in the "the second generation of Grubbs Catalyst", and work with Dr. Rees resulted in a 0.7 angstrom DNA structure. After he graduated from Caltech in 1999, he joined Dr. Peter Schultz lab at the Scripps Research Institute to conduct his Ph.D. studies, which opened up new avenues for developing future regenerative medicine. He then started his independent career as an Assistant Professor in the Chemistry Department at Scripps by the end of 2003. Since early 2007, Ding has been an Associate Professor at Scripps.
A current curriculum vitae for Professor Ding is available.