Dr. Youn’s long-term research interests are investigating the molecular mechanisms of cardiovascular and pathological disease conditions. His academic training and research experiences have provided an excellent background in molecular biology, vascular biology, and stem cell biology. Dr. Youn has a strong background in vascular biology and expertise in genetic engineering, molecular signaling, real-time imaging, and vascular functional assays. He is also a research assistant professor in Dr. Kitajewski’s Lab and a director for UIC Viral Vector Core.

Notch signaling:

Notch signaling in endothelial cells plays a central role in angiogenesis and lymphangiogenesis. Endothelial Notch signaling suppresses tip cell formation, migration, and proliferation while promoting barrier formation. Notch activity is highly dynamic in sprouting endothelial cells, while constitutive Notch signaling drives homeostatic endothelial polarization, indicating the need for both rapid and constitutive Notch targets.

Together with Dr. Kitejewski’s lab, Dr. Youn characterized the dynamic response to Notch with translatomic and biological analysis that concludes RND1, the rapid highest induction gene, is directly regulated by endothelial Notch signaling to suppress endothelial migration. They also found a novel candidate of Notch targets, Unc5B, to regulate endothelial proliferation, migration, junction activity, and retinal plexus branching. They recently developed peptibodies of Notch1 and Notch4, which specifically inhibit the function of Notch1 and Notch4 in vitro and in vivo angiogenesis.

Liver and Cardiovascular disease:

Obesity, aging, and metabolic diseases are linked to metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by fat accumulation leading to liver dysfunction. Metabolic dysfunction-associated steatohepatitis (MASH), an inflammatory state of MASLD, is increasing in incidence among the U.S. population. MASH develops through fat accumulation, fibrosis, inflammation, and pathological angiogenesis in the liver. This process can lead to cirrhosis and liver failure or hepatocellular carcinoma (HCC). At present, there are no approved pharmacotherapies for MASH cirrhosis, and a definitive cure requires liver transplantation, which is limited by patient tolerance and access to donor organs.

The liver vasculature is unique compared to the vascular systems of other organs. Sinusoidal vessels are lined by liver sinusoidal endothelial cells (LSEC), characterized by fenestrae that allow free passage of macromolecules such as fatty acids out of the bloodstream. During liver disease pathogenesis, LSECs rapidly transition to an arterial phenotype through “capillarization,” in which liver vasculature no longer maintains hepatic homeostasis, leading to inflammation, fibrosis, and organ dysfunction.

MASH has also been linked to an increased risk of cardiovascular disease (CVD), and CVD is the leading cause of morbidity and mortality in patients with MASLD/MASH. Recent works indicated that the increased vascular growth factor C (VEGFC) during liver disease progression accelerated disease severity through LSECs. Thus, Dr. Youn’s current works focus on how pathological angiogenesis regulates the acceleration of MASH and HCC development and CVD progression.