Hao Huang
Education & Experience

2016-present    Principle Investigator, Peking University, Shenzhen Graduate School

2015 -2016       Senior Research Scientist (permanent position), Astex Pharmaceuticals, Cambridge, UK

2011 -2015       Postdoctoral Fellow, Mount Sinai Hospital-Toronto & University of Toronto, Canada (Supervisor: Dr. Frank Sicheri)

2006-2011        Ph. D in Biochemistry, University of Calgary, Canada (Supervisor: Dr. Hans Vogel)

2004-2005        M.Sc. in Chemistry, McMaster University, Canada

1999-2002        M.Sc. in Analytical Chemistry, Tsinghua University

1995-1999        B.Sc. in Biology, Sichuan University

Awards & Honors

2017        Bayer-PKU Investigator

2014        Canadian Institutes of Health Research (CIHR) postdoctoral fellowship

2008        Alberta Heritage Foundation for Medical Research (AHFMR) Ph.D studentship

Research Fields

The Hao Huang lab aims to discover small molecular anticancer/antiviral drug leads. We employ Fragment Based Drug Discovery (FBDD) and structure-based drug design (SBDD) to discover inhibitors targeting important proteins in cancer signaling pathways. In the process of discovering novel anticancer drugs, we use integrative approaches of structural biology, chemical biology and medicinal chemistry. Specifically, we pursue drug discovery in the ubiquitin-proteasome system (UPS).

We are also conducting cell biology research on signal transduction closely related to cancers in the UPS, hoping to understand the regulatory roles of oncogenes and tumor suppressors, as well as to identify new anti-cancer drug targets.

In the research of kinases, we are interested in the discovery of small molecular inhibitors for disease-related target proteins and the working mechanisms. We have extensive experiences in the research of pseudokinase-ribonuclease L (RNase L), and we are currently testing some unique ideas.

Self-motivated students, postdocs and research associates are encouraged to contact me if you are interested in joining our research lab.

 

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Selected Publications


1Cao D#, Duan L#, Huang B#, Xiong Y, Zhang G*, Huang H*, The SARS-CoV-2 papain-like protease suppresses type I interferon responses by deubiquitinating STING, Sci. Signal., 2023,16(783):eadd0082.

2Xiong Y#, Huang B#, Yang Y, Fu X, Fu Z, Xu H, Liu M, Cao D, Zhang M, Yang H, Niu X, Yu C, Huang H, Papain-like proteases from seven human-infecting coronaviruses differ in substrate selectivity and innate immune suppression, Sci. Signal., 2023,16(783):eade1985.

3Tang J#, Dong B#, Liu M, Liu S, Niu X, Gaughan C, Asthana A, Zhou H, Xu Z, Zhang G, Silverman RH*, Huang H*. Identification of Small Molecule Inhibitors of RNase L by Fragment-Based Drug Discovery, J Med Chem. 2022, 65(2):1445-1457.  

4Fu Z#, Huang B#, Tang J#, Liu S#, Liu M, Ye Y, Liu Z, Xiong Y, Zhu W, Cao D, Li J, Niu X, Zhou H, Zhao YJ, Zhang G*, Huang H*, The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery, Nat Commun. 2021;12(1):488.

5Ye Y#, Xiong Y#, Huang H., Substrate-binding destabilizes the hydrophobic cluster to relieve the autoinhibition of bacterial ubiquitin ligase IpaH9.8, Commun Biol. 2020;3(1):752.

6Tang J#, Wang Y#, Zhou H#, Ye Y, Talukdar M, Fu Z, Liu Z, Li J, Neculai D, Gao J, Huang H, Sunitinib inhibits RNase L by destabilizing its active dimer conformation , Biochem J . 2020;477(17):3387-3399.

7Daou S#, Talukdar M#, Tang J#, Dong B, Banerjee S, Li Y, Duffy NM, Ogunjimi AA, Gaughan C, Jha BK, Gish G, Tavernier N, Mao D, Weiss SR, Huang H*, Silverman RH*, Sicheri F*, A phenolic small molecule inhibitor of RNase L prevents cell death from ADAR1 deficiency, Proc Natl Acad Sci U S A.  2020;117(40):24802-24812.

8Huang H, Zeqiraj E, Dong B, Jha BK, Duffy NM, Orlicky S, Thevakumaran N, Talukdar M, Pillon MC, Ceccarelli DF, Wan LC, Juang YC, Mao DY, Gaughan C, Brinton MA, Perelygin AA, Kourinov I, Guarné A, Silverman RH, Sicheri F, Dimeric structure of pseudokinase RNase L bound to 2-5A reveals a basis for interferon induced antiviral activity.  Mol. Cell. 2014; 53, 221-34

Recommended in F1000, http://f1000.com/prime/718246713;

Highlighted in Cell 157, 2014: http://www.cell.com/cell/pdf/S0092-8674(14)00487-5.pdf

9Huang H*, Ceccarelli DF*, Orlicky S*, St-Cyr DJ, Ziemba A, Garg P, Plamondon S, Auer M, Sidhu S, Marinier A, Kleiger G, Tyers M, Sicheri F, E2 enzyme inhibition by stabilization of a low-affinity interface with ubiquitin. Nat. Chem. Biol. 2014 10, 156-63

10Fradet-Turcotte A, Canny MD, Escribano-Díaz C, Orthwein A, Leung CC, Huang H, Landry MC, Kitevski-LeBlanc J, Noordermeer SM, Sicheri F, Durocher D. 53BP1 is a reader of the DNA-damage-induced H2A Lys15 ubiquitin mark. Nature. 2013, 499, 50-54.

11Rivkin E, Almeida SM, Ceccarelli DF, Juang YC, MacLean TA, Srikumar T, Huang H, Dunham WH, Fukumura R, Xie G, Gondo Y, Raught B, Gingras AC, Sicheri F, Cordes SP. The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis. Nature. 2013, 498, 318-24

12Huang H and Vogel HJ, Structural Basis for the Activation of the Cytoplasmic Domain of the Human Platelet Integrin AlphaIIb-beta3 by CIB1. J. Am. Chem. Soc., 2012, 134, 3864-72Highlighted in Science Dailyhttp://www.sciencedaily.com/releases/2012/03/120319095011.htm



Patents

Tyers M, Sicheri F, Ceccarelli DF, Huang H, et al., Screening methods to identify compounds inhibiting the activity of E2 enzymes by stabilization of non-covalent ubiquitin-E2 complexes and pharmaceutical applications related to E2 inhibitors. Application #: PCT/CA2013/001079;