Email: jhhu@sioc.ac.cn
Phone: 021-6858 2261
Office: 100 Haike Rd, #13, Room 323
Website:
Principal Investigator, Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences.
Postdoctoral Fellow, German Cancer Research Center (DKFZ) (2008-2014)
Ph.D., Shanghai Institute for Biological Sciences (2002-2007)
B.Med, Anhui University of Science and Technology (1997-2002)
Dr. Junhao Hu's research interests focus on understanding the crosstalk between endothelial cells and pericytes, which constitute the blood vessel wall, as well as how such crosstalk controls vascular function and organ homeostasis.
The blood vessels, which consist of endothelial cells and mural cells (the vascular smooth muscle cells and pericytes), are conduits for the exchange of oxygen, nutrients, and metabolic waste. However, during the past decade, emerging evidence has demonstrated that blood vessel-derived paracrine signals play an essential role in many physiopathological conditions, including organ development, regeneration, tumor metastasis, etc. However, the molecular nature of these inter- and intracellular communication is not fully understood.
Endothelial cell–pericyte interaction in health and disease
The crosstalk between endothelial cells and pericytes is essential for angiogenesis, vessel remodeling, and vessel maturation. Dysregulation of endothelial cell–pericyte interaction results in excessive angiogenesis and impaired vascular integrity, which are key pathological changes of a variety of diseases, including cancer, diabetic retinopathy, liver fibrosis, lung edema, and neurodegenerative diseases. Our interest lies in systematically mapping the endothelial cell–pericyte interactome in the lung, liver and brain under healthy and pathological conditions. Based on the mechanistic insight that is provided by the interactome, we would further explore whether targeting specific endothelial cell–pericyte crosstalk or blood vessel-derived signaling could provide a therapeutic benefit for the treatment of diseases, including ARDS, liver fibrosis, and cerebral small vessel disease.
Vessel size determination and maintenance
The lumen size of mature blood vessels is quite stable; however, it could undergo vessel remodeling under certain conditions, such as the enlargement of collateral vessels that connect the ischemic tissue. It is well accepted that both the blood flow and the metabolic demand of surrounding tissue play important roles in determining vessel size. However, whether there exist intrinsic pathways that actively control a vessel’s lumen size remains elusive. We are currently utilizing a microfluidic-based vessel formation system and genetic mouse models to explore the endothelial cell-intrinsic mechanisms that determine and maintain vessel diameter.
Hu J*, Srivastava K*, Wieland M, Runge A, Mogler C, Besemfelder E, Terhardt D, Vogel M, Cao L, Korn C, Bartels S, Thomas M, Augustin H. Endothelial cell-derived angiopoietin-2 controls liver regeneration as a spatiotemporal rheostat. Science. 343: 416–419. (2014). (*, co-first authors).
Srivastava K*, Hu J*, Korn C, Savant S, Teichert M, Kapel S, Jugold M, Besemfelder E, Thomas, M, Pasparakis M, Augustin H. Postsurgical Adjuvant Tumor Therapy by Combining Anti-Angiopoietin-2 and Metronomic Chemotherapy Limits Metastatic Growth. Cancer Cell. 26: 880–895. (2014). (*, co-first authors).
Singhal M*, Liu X*, Inverso D, Jiang K, Dai J, He H, Bartels S, Li W, Abdul Pari AA, Gengenbacher N, Besemfelder E, Hui L, Augustin H#, Hu J#. Endothelial cell fitness dictates the source of regenerating liver vasculature. Journal of Experimental Medicine. 215: 2497–2598. (2018). (*, co-first authors; #, co-corresponding authors).
Hu C*, Li W*, Tian F, Jiang K, Liu X, Cen J, He Q, Qiu Z, Keenest Y, Wang Z, Zhang H, Ji Y#, Hu J#, Hui L#. Arid1a regulates response to anti-angiogenic therapy in advanced hepatocellular carcinoma. Journal of Hepatology. 68: 465–475. (2018). (*, co-first authors; #, co-corresponding authors).
Dai J, Zhang C, Guo L, He H, Kai J, Huang Y, Zhang X, Zhang H, Wei W, Zhang Y, Lu L#, Hu J#. A necroptotic-independent function of MLKL in regulating endothelial cell adhesion molecule expression. Cell Death and Disease. 11: 282 (2020). (#, co-corresponding authors).
Yang W*, He H*, Wang T, Su N, Zhang F, Jiang K, Zhu J, Zhang C, Niu K, Wang L, Yuan X, Liu N, Li L, Wei W, Hu J. Single-cell transcriptomic analysis reveals a hepatic stellate cell-activation roadmap and myofibroblast origin during liver fibrosis. Hepatology. 74: 2774–2790. (2021). (*, co-first authors).
Zhang C, He H, Dai J, Li Y, He J, Yang W, Dai J, Han F, Kong W, Wang X, Zheng X, Pan W, Chen Z, Singhal M, Zhang Y, Guo F#, Hu J#. KANK4 promotes arteriogenesis by potentiating VEGFR2 signaling in a TALIN-1–dependent manner. Arteriosclerosis, Thrombosis, and Vascular Biology. 42:772-788. (2022).