Yanning Rui
Assistant Professor
University of Texas Health Science Center at Houston
McGovern Medical School
Department of Neurosurgery
Autophagy, a fundamental process of intracellular self-digestion, plays a pivotal role in maintaining the quality control of diverse organelles such as mitochondria, endoplasmic reticulum (ER), and aggresomes. The turnover of distinct organelle types necessitates unique cargo receptors, which identify organelle-specific resident proteins and ferry them to autophagosomes—the central machinery responsible for conveying cargos to lysosomes for degradation. This orchestrated deployment of distinct cargo receptors in selective autophagy ensures the precise turnover of designated organelles under both physiological and pathological contexts. The emergence of deleterious rare variants in these cargo receptors, coupled with the disruption of selective autophagy, has been implicated in a spectrum of human diseases encompassing cerebrovascular disorders and neurodegenerative conditions. Our laboratory has demonstrated a longstanding commitment to unraveling the intricate molecular mechanisms of selective autophagy in vascular cells, with a particular focus on discerning its implications in stroke and stroke-related dementia.
More recently, we have identified a new type of selective autophagy, characterized by the targeted degradation of focal adhesions (FAs) within endothelial cells. We are actively delineating the contributions of dysregulated FA-phagy—an autophagy-mediated process governing the specific turnover of FAs—to the landscape of cerebrovascular disorders. Employing a strategic combination of zebrafish and murine models, we have established platforms to mimic the pathophysiological conditions observed in stroke patients. An advantage of the zebrafish model is its transparent embryos, enabling direct microscopic observation of fluorescence-labeled vessels and blood cells. Manipulation of vascular integrity in zebrafish engenders intracranial hemorrhage, a phenomenon reminiscent of the clinical presentation in stroke patients. Meanwhile, intricate manifestations, including intracranial aneurysms and cognitive impairments, are explored within murine models. Our investigative endeavors extend to the evaluation of cerebral vasculature and integrity, leveraging an array of advanced imaging methodologies amenable to live mice. Magnetic resonance imaging is used to detect aneurysm formation, growth and rupture, while two-photon microscopy affords the opportunity to examine vascular cell dynamics within cortical domains.
Unified by the synergy of dual animal models and cutting-edge imaging platforms, our laboratory is dedicated to elucidating the molecular mechanisms governing FA-phagy within vascular cells. Understanding the role of FA-phagy in the context of stroke, we aim to reveal innovative therapeutic targets with potential benefits for patients affected by this condition.
Education & Training
PhD - Hong Kong University of Science and Technology - 2007