Understanding the Two Faces of the Human BIGH3 Protein: BIGH3 Roles in Diabetes and Cancer
Dr. LeBaron's research program is focused on the mechanisms that allow eucaryotic cells to interact with molecules of the extracellular matrix (ECM). Central to his research program is the mentorship and career development of underrepresented students and non-underrepresented students at the undergraduate, master's, and doctoral levels. Students investigate sectors of cell biology regarding roles of ECM molecules in health and disease. Different cell types collaborate using receptor mediated inter- and intra-cellular signaling to control cellular synthesis of three dimensional proteinaceous ECMs in the creation, repair and regeneration of functional tissues.
An overarching goal in Dr. LeBaron's research program is to better comprehend ECM roles in the regenerative process. One objective is to understand the biology of a proapoptotic ECM protein called BIGH3. His lab's research has shown that BIGH3 is important in the progression of diabetic complications in human renal, ocular and cardiovascular systems. Interestingly, a similar BIGH3 mechanism is intimately involved in human cancer progression, thus explaining his investigative probes of BIGH3 in diabetes and cancer. The lab has recently identified the BIGH3-derived signals that induce apoptosis. Moreover, they now have evidence that a specific cell-surface receptor is involved in the apoptotic pathway, and have linked the pathway to macrophages and TGF-β1. Immediate goals are to delineate the cytosolic pathway that propels BIGH3-mediated apoptosis, and identify targets for diabetic and cancer therapeutic interventions.
The second interest of Dr. LeBaron's research program is in the field of tissue engineering. Previously the lab had generated human-equivalent skin and articular cartilage tissues ex vivo, that is, outside the body using a bioreactor. They are currently exploring the role that BIGH3 plays in generation of engineered tissues, and BIGH3's potential signaling to stem cell proliferation and differentiation in the context of tissue engineering applications. The lab collaborates with a team of cell biologists, biochemists and tissue engineers at UTSA, UT Health San Antonio, and UC Davis in order to best understand ECM and cellular interactions in healthy and diseased tissues.
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