Our research program delves into the intricate molecular mechanisms governing pathological cell death. Dysregulation of cell death pathways is a common occurrence in various human diseases, including ischemic injuries, degenerative diseases, cancer, and aging. Gaining a deeper understanding of cell death pathways during these disease states is crucial for identifying novel therapeutic targets that can effectively prevent or induce cell death as required.

 

Our primary research focus centers around uncovering the molecular mechanisms underlying the regulated necrotic pathway in cardiac ischemic injuries. Given the high reliance of cardiomyocytes on mitochondrial ATP production, mitochondrial dysfunction lies at the core of numerous cardiomyopathies. One of the primary contributors to this dysfunction is the mitochondrial permeability transition pore (mPTP), which plays a significant role in heart-related issues. In our previous work, we made significant progress by identifying the outer mitochondrial membrane regulators of the mPTP, Bax, and Bak. This discovery revealed a pivotal point connecting the apoptotic and necrotic cell death pathways. Additionally, my research centers on investigating the molecular identity of the inner mitochondrial membrane pore-forming component of the mPTP. Recently, we successfully genetically inhibited the mPTP in mice, leading to the formulation of a hypothesis involving multiple pore-forming components.

 

Furthermore, our program has conducted numerous genome-wide overexpression screens to identify novel regulators of cell death, and we are currently conducting in vivo studies to explore these candidates further. By building on established knowledge of cell death pathways, our program aims to elucidate overlaps, crosstalk, and, most importantly, uncover new regulators that could hold the key to future therapeutic interventions.