Dongming Cai MD, PhD

Icahn School of Medicine at Mount Sinai

Dr. Dongming Cai has a broad background in neuroscience, with specific training and expertise in key research areas for studies in aging and neurodegenerative disorders. During her postdoctoral training at Laboratory of Paul Greengard of The Rockefeller University, she carried out research studies focusing on characterization of the impact of phospholipase D1 (PLD1) on APP processing and trafficking. Studies suggest that the Aβ-lowering effect of PLD1 is independent of its ability to promote vesicular budding of APP. At Yale School of Medicine, Dr. Cai expanded her research to investigate the regulation of membrane lipid composition, metabolism and its effects on AD. Since she joined Icahn School of Medicine at Mount Sinai as a faculty, the research program has been focused on studying the regulation of phospholipid composition and metabolism in AD pathogenesis. Recent evidence from his lab demonstrates a novel regulatory role for synaptojanin 1 (synj1) in Alzheimer’s disease, by which reduction of synj1 facilitates cellular Aβ clearance through endosomal/lysosomal system, and attenuates amyloid-induced neuropathologic changes. More importantly, she has observed changes in PIP2 homeostasis and synj1 expression levels in ApoE4 brains if compared to ApoE3 counterparts. Reduction of synj1 can rescue cognitive deficits in an AD transgenic mouse model (Swedish APP/PS1E9) and in an ApoE4 knock-in (KI) mouse model. The findings uncover novel roles for reducing synj1 expression in AD therapies (amyloid clearance and reversing ApoE4 pathogenic nature). One of his current research projects is to develop preclinical candidates and new chemical scaffolds that can lower synj1 expression for AD therapies. More importantly, she will investigate mechanistic actions of newly developed drug candidates on lowering brain synj1 levels and restoring phospholipid dysregulation in AD which will shed lights on understanding pathways underlying ApoE-regulated synj1 expression. Other projects in the lab are focusing on exploring the interaction between ApoE4 and other risk factors of AD such as TBI, sex and vascular comorbidities in AD development and progression. In summary, Dr. Cai has demonstrated record of productive research projects in an area of high relevance for our aging population, and her expertise and experience has prepared her to lead the projects.