Division of Endocrinology, Diabetes & Metabolic Diseases
My training and experience include clinical medicine, basic research, and industrial drug development. Since 2007, I have been involved in a few drug discovery programs (β-secretase inhibitor, α7-nicotinic agonist and β-amyloid oligomer inhibitor for Alzheimer’s disease; allosteric hemoglobin modulator for hypoxia-related conditions), in which I headed pharmacology & pharmacokinetics, supporting lead optimization, ADME, PK/PD, dose projection, IND enabling, and clinical development. The work from my team contributed to advancing several small molecule drugs into clinical trials, and a co-development partnership deal worth ~$760M in 2008. I came back to academia in 2013 with the realization: 1) that the bottleneck of therapeutic development lies in the rather difficult basic-to-clinical translation, and 2) that a current trend of shifting early drug discovery to academia may bring translational opportunities.
The overall goal of the research in my lab is to facilitate the translation of important sciences into the clinic. This includes identifying biomarkers, disease mechanisms and drug targets, and developing new treatments employing creative strategies such as drug repurposing. One current focus is preeclampsia and related vascular disorders of diabetes. Preeclampsia is a leading complication of pregnancy that affects 3 to 5% of women in general and 4-fold more in those with high-risk conditions such as diabetes. It is characterized by new-onset hypertension with proteinuria during the 2nd half of gestation. Its etiology remains elusive, and there is no effective, targeted therapy. However, there have been some recent advances in our understanding of its pathogenesis, including the increased release of anti-angiogenic factors soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng) from the placenta, which cause maternal vascular endothelial cell injury (a central pathology of preeclampsia). Exploiting these important mechanisms, we have developed novel cell-based models and screened a library of clinical drugs with favorable safety features. We are currently validating the preclinical efficacy and pharmacological profiles of a list of candidate drugs in order to support a future clinical trial(s). This work has been funded by the ‘Saving Lives at Birth - A Grand Challenge’ (jointly by the USAID, Government of Norway, Gates Foundation, Grand Challenges Canada, and UKAID), and more recently by the NIH/NICHD.