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Jenny Zhou Lab
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    Cerebral cavernous malformations

    Cerebral cavernous malformations (CCMs) are common vascular malformations with a prevalence of 0.4-0.8% that affect the vasculature of central nervous system in the human population where they result in increased risk for stroke, seizures and focal neurological deficits.

    My research aims to address the following fundamental questions:

    • Why are CCM lesions primarily confined to brain vasculature despite CCM proteins are ubiquitously expressed in all tissues?
    • Which is the major cell type in which CCM loss initiates CCM lesion formation?
    • And what is the critical signaling in endothelial cells and pericytes that contributes to CCM disease?
    I expand my current study of CCM3 to explore the hypothesis that loss of CCM3 in endothelial cells (EC) and pericytes (PC) alters signaling critical for EC-PC interactions, contributing to vascular disassembly and capillary dilation within the neurovascular unit, leading to CCM (Nat Med, 2016; Arterioscler Thromb Vasc Biol, 2020; Nat Commun, 2021). Furthermore, CCM3 deletion augments the VEGFR3-ERK1/2 signaling in lymphatic endothelial cells that drives lymphatic hyperplasia and malformation and warrant further investigation on the potential clinical relevance of lymphatic dysfunction in patients with CCM (Arterioscler Thromb Vasc Biol, 2021). We will use the complementary approaches of genetic, cell biological and imaging analyses to define augmented membrane protein targeting in a specialized cell type within neurovascular unit as the causes of CCM pathology, and define new and more effective therapies for this potentially debilitating neurological disorder.

    Elucidate critical function of mitochondrial protein in retinopathy

    Mitochondrial dysfunction is involved in the pathogenesis of the major blinding retinal diseases such as diabetic retinopathy and age-related macular degeneration, but study on mitochondria in retinal vasculature is limited. We will employ genetic, biochemical, cell biology, microscopy imaging and single cell transcriptome analyses to define the angiogenic and metabolic pathways regulated by mitochondrial proteins with distinct functions, which will facilitate our understanding of the molecular mechanisms and pathogenesis involved in vascular diseases in the eye, and help in defining more effective therapies.