Jenny Huanjiao Zhou, MD, PhD
Research & Publications
Biography
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Research Summary
I have focused on translational research from the very beginning of my postgraduate study. To discover the molecular mechanisms and facilitate new therapeutic strategies for vascular diseases, I have worked on angiogenesis and lymphangiogenesis, predominantly to investigate the role of CCM3, Trx2, SENP1 and AIP1 genes in animal models and in vitro for vascular biology, cell biology and signaling, as well as potential therapeutic targets which would provide promising treatment for vascular diseases such as cerebral cavernous malformation, diabetic retinopathy and cardiomyopathy. Specifically, I have 1) defined novel function of AIP1 and CCM3 in regulating VEGFR3 signaling in angiogenesis and lymphangiogenesis (Arterioscler Thromb Vasc Biol, 2014;Arterioscler Thromb Vasc Biol, 2021); 2) elucidated critical function of mitochondrial redox protein Trx2 in cardiomyopathy in collaboration with Dr. Huang in the lab (Circulation, 2015), and found Trx2 modulates vessel sprouting and maturation in angiogenesis (ongoing work); 3) demonstrated that SENP1 functions as an endogenous activator in VEGFR2 signalling by regulating VEGFR2 trafficking from the Golgi to endothelial cell surface which pathway plays a critical role in diabetes-associated angiogenesis (Nat Commun, 2018); 4) established inducible endothelial-specific CCM3 mouse model for human cerebral cavernous malformation (CCM) disease and have intriguingly found that blockade of exocytosis or inhibition of Angpt2-TIE2 signaling completely blunts CCM lesion formation in the mouse model (Nat Med, 2016; Nat Commun, 2021).
News and Views at: http://www.nature.com/nm/journal/v22/n9/full/nm.4178.html
Yale News at: http://news.yale.edu/2016/08/22/research-note-study-uncovers-marker-chronic-brain-disease.
Yale News at: https://yaledailynews.com/blog/2016/09/13/potential-therapy-found-for-vascular-disease/
Extensive Research Description
Ongoing Projects:
1. 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). I 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.
2. Elucidate critical function of mitochondrial redox protein in vascular diseases:Thioredoxin 2 (Trx2) is a key mitochondrial protein that regulates cellular redox and survival by suppressing mitochondrial reactive oxygen species generation. Because mice with a constitutive deletion of Trx2 in endothelial cell were lethal, I generated endothelial-specific tamoxifen-inducible Trx2 loss-of-function mice, and am investigating the role of Trx2 in retina angiogenesis and retina diseases.
Positions available (for Students, Postdocs and Visiting Scholars): We are open to highly motivated postgraduate students and postgraduates including visiting scholars who has MD degree, PhD degree/candidate, both MD and PhD degree/candidate, to work on exciting on-going directions, especially vascular biology and malformations, vascular diseases (CCM, AVM, Eye diseases and Lymphatic diseases) and translational perspectives. We prefer someone who is experienced in both in vivo and in vitro study. Please contact me directly (jenny.zhou@yale.edu) with your updated CV if you are interested.
Coauthors
Research Interests
Arteriovenous Malformations; Blood Vessels; Blood-Brain Barrier; Cardiovascular Diseases; Endothelium
Public Health Interests
Cardiovascular Diseases
Selected Publications
- AIP1 mediates vascular endothelial cell growth factor receptor-3-dependent angiogenic and lymphangiogenic responses.Zhou HJ, Chen X, Huang Q, Liu R, Zhang H, Wang Y, Jin Y, Liang X, Lu L, Xu Z, Min W. AIP1 mediates vascular endothelial cell growth factor receptor-3-dependent angiogenic and lymphangiogenic responses. Arteriosclerosis, Thrombosis, And Vascular Biology 2014, 34: 603-15. PMID: 24407031, PMCID: PMC3952062, DOI: 10.1161/ATVBAHA.113.303053.
- Thioredoxin-2 inhibits mitochondrial reactive oxygen species generation and apoptosis stress kinase-1 activity to maintain cardiac function.Huang Q, Zhou HJ, Zhang H, Huang Y, Hinojosa-Kirschenbaum F, Fan P, Yao L, Belardinelli L, Tellides G, Giordano FJ, Budas GR, Min W. Thioredoxin-2 inhibits mitochondrial reactive oxygen species generation and apoptosis stress kinase-1 activity to maintain cardiac function. Circulation 2015, 131: 1082-97. PMID: 25628390, PMCID: PMC4374031, DOI: 10.1161/CIRCULATIONAHA.114.012725.
- Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation.Zhou HJ, Qin L, Zhang H, Tang W, Ji W, He Y, Liang X, Wang Z, Yuan Q, Vortmeyer A, Toomre D, Fuh G, Yan M, Kluger MS, Wu D, Min W. Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation. Nature Medicine 2016, 22: 1033-1042. PMID: 27548575, PMCID: PMC5014607, DOI: 10.1038/nm.4169.
- SUMOylation of VEGFR2 regulates its intracellular trafficking and pathological angiogenesis.Zhou HJ, Xu Z, Wang Z, Zhang H, Simons M, Simons M, Min W. SUMOylation of VEGFR2 regulates its intracellular trafficking and pathological angiogenesis. Nature Communications 2018, 9: 3303. PMID: 30120232, PMCID: PMC6098000, DOI: 10.1038/s41467-018-05812-2.
- Author Correction: SUMOylation of VEGFR2 regulates its intracellular trafficking and pathological angiogenesis.Zhou HJ, Xu Z, Wang Z, Zhang H, Zhuang ZW, Simons M, Min W. Author Correction: SUMOylation of VEGFR2 regulates its intracellular trafficking and pathological angiogenesis. Nature Communications 2019, 10: 3679. PMID: 31417083, PMCID: PMC6695411, DOI: 10.1038/s41467-019-11659-y.
- Caveolae-mediated Tie2 signaling contributes to CCM pathogenesis in a brain endothelial cell-specific Pdcd10-deficient mouse model.Zhou HJ, Qin L, Jiang Q, Murray KN, Zhang H, Li B, Lin Q, Graham M, Liu X, Grutzendler J, Min W. Caveolae-mediated Tie2 signaling contributes to CCM pathogenesis in a brain endothelial cell-specific Pdcd10-deficient mouse model. Nature Communications 2021, 12: 504. PMID: 33495460, PMCID: PMC7835246, DOI: 10.1038/s41467-020-20774-0.
- Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations.Wang K, Zhang H, He Y, Jiang Q, Tanaka Y, Park IH, Pober JS, Min W, Zhou HJ. Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations. Arteriosclerosis, Thrombosis, And Vascular Biology 2020, 40: 2171-2186. PMID: 32640906, DOI: 10.1161/ATVBAHA.120.314586.
- CCM3 Loss-Induced Lymphatic Defect Is Mediated by the Augmented VEGFR3-ERK1/2 Signaling.Qin L, Zhang H, Li B, Jiang Q, Lopez F, Min W, Zhou JH. CCM3 Loss-Induced Lymphatic Defect Is Mediated by the Augmented VEGFR3-ERK1/2 Signaling. Arteriosclerosis, Thrombosis, And Vascular Biology 2021, 41: 2943-2960. PMID: 34670407, PMCID: PMC8613000, DOI: 10.1161/ATVBAHA.121.316707.
- SENP1-mediated NEMO deSUMOylation in adipocytes limits inflammatory responses and type-1 diabetes progression.Shao L, Zhou HJ, Zhang H, Qin L, Hwa J, Yun Z, Ji W, Min W. SENP1-mediated NEMO deSUMOylation in adipocytes limits inflammatory responses and type-1 diabetes progression. Nature Communications 2015, 6: 8917. PMID: 26596471, PMCID: PMC4662081, DOI: 10.1038/ncomms9917.
- Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer.Yin M, Li X, Tan S, Zhou HJ, Ji W, Bellone S, Xu X, Zhang H, Santin AD, Lou G, Min W. Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer. The Journal Of Clinical Investigation 2016, 126: 4157-4173. PMID: 27721235, PMCID: PMC5096908, DOI: 10.1172/JCI87252.
- ASK1-dependent endothelial cell activation is critical in ovarian cancer growth and metastasis.Yin M, Zhou HJ, Zhang J, Lin C, Li H, Li X, Li Y, Zhang H, Breckenridge DG, Ji W, Min W. ASK1-dependent endothelial cell activation is critical in ovarian cancer growth and metastasis. JCI Insight 2017, 2 PMID: 28931753, PMCID: PMC5621912, DOI: 10.1172/jci.insight.91828.
- Stromal Senp1 promotes mouse early folliculogenesis by regulating BMP4 expression.Tan S, Feng B, Yin M, Zhou HJ, Lou G, Ji W, Li Y, Min W. Stromal Senp1 promotes mouse early folliculogenesis by regulating BMP4 expression. Cell & Bioscience 2017, 7: 36. PMID: 28770041, PMCID: PMC5526272, DOI: 10.1186/s13578-017-0163-5.
- Critical role of Lin28-TNFR2 signalling in cardiac stem cell activation and differentiation.Xiang Q, Yang B, Li L, Qiu B, Qiu C, Gao XB, Zhou HJ, Min W. Critical role of Lin28-TNFR2 signalling in cardiac stem cell activation and differentiation. Journal Of Cellular And Molecular Medicine 2019, 23: 0. PMID: 30734494, PMCID: PMC6433861, DOI: 10.1111/jcmm.14202.
- CD34+KLF4+ Stromal Stem Cells Contribute to Endometrial Regeneration and Repair.Yin M, Zhou HJ, Lin C, Long L, Yang X, Zhang H, Taylor H, Min W. CD34+KLF4+ Stromal Stem Cells Contribute to Endometrial Regeneration and Repair. Cell Reports 2019, 27: 2709-2724.e3. PMID: 31141693, PMCID: PMC6548470, DOI: 10.1016/j.celrep.2019.04.088.
- Short AIP1 (ASK1-Interacting Protein-1) Isoform Localizes to the Mitochondria and Promotes Vascular Dysfunction.Li Z, Li L, Zhang H, Zhou HJ, Ji W, Min W. Short AIP1 (ASK1-Interacting Protein-1) Isoform Localizes to the Mitochondria and Promotes Vascular Dysfunction. Arteriosclerosis, Thrombosis, And Vascular Biology 2020, 40: 112-127. PMID: 31619063, PMCID: PMC7204498, DOI: 10.1161/ATVBAHA.119.312976.
- BMX Represses Thrombin-PAR1-Mediated Endothelial Permeability and Vascular Leakage During Early Sepsis.Li Z, Yin M, Zhang H, Ni W, Pierce R, Zhou HJ, Min W. BMX Represses Thrombin-PAR1-Mediated Endothelial Permeability and Vascular Leakage During Early Sepsis. Circulation Research 2020, 126: 471-485. PMID: 31910739, PMCID: PMC7035171, DOI: 10.1161/CIRCRESAHA.119.315769.
- Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance.He F, Huang Y, Song Z, Zhou HJ, Zhang H, Perry RJ, Shulman GI, Min W. Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance. The Journal Of Experimental Medicine 2021, 218 PMID: 33315085, PMCID: PMC7927432, DOI: 10.1084/jem.20201416.