Biography: Dr. Mingdong Huang obtained his PhD degree in Chemistry from Oregon State University of USA. After post-doctoral training in The Scripps Research Institute with Ian A. Wilson, he took a faculty position in Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA. His research was funded by grants from NIH (RO1), American Heart Association, and biomedical industry. In 2003, he took the position of director of the Division of Chemical Biology in Fujian Institute of Research on the Structure of Matter (FJIRSM), Chinese Academy of Sciences, and started a chemical biology program in the institute. He moved to Fuzhou University in 2016.
Research directions: One of Dr. Huang main research focuses is on the studies of crystal structures and the development of modulators of various vascular proteins, especially proteins in haemostatic and fibrinolytic processes. He determined the crystal structures of a series of important vascular proteins, notably the structures of urokinase receptor (uPAR) and its complex with urokinase and vitronectin, which was published in Science. This work re-kindles research interest in developing uPAR inhibitors to intervene with cancer metastasis.
(1) Chemical biology. We developed a technology for biomedical imaging and cancer therapy. We synthesized a unique fluorescent probe (CPZ or beta-carboxy-phthalocyanine zinc, https://www.sciencedirect.com/science/article/pii/S1387700305004077) in large quantity (commercially available at http://fmerc.fzu.edu.cn/html/hzjl/2018/09/29/73bc2f2c-d6bd-461b-b95e-bb08a336f9a3.html). This compound has three important features: (a) high stability and strong fluorescence (ex610nm/em690nm); (b) generation of reactive oxygen species (ROS) when illuminated at 680nm; (c) chemical expandability: CPZ contains a carboxy group that can be easily conjugated to peptide or proteins. We conjugated CPZ to various peptides: (a) urokinase receptor targeting peptide (ATF); (b) polylysine peptide; (c) Gonadotropin-releasing hormone (GnRH) peptide targeting at GnRH receptor, and demonstrated the tumor targeting capability of the conjugates in mice models. We also used the lysine-conjugated CPZ for antimicrobial applications and demonstrated that it inactivated drug resistant bacterial strains. This conjugate was later found practical applications as antimicrobial additive and antimicrobial fabric materials. For list of publications, see https://www.ncbi.nlm.nih.gov/pubmed/?term=Huang%2CMingdong%5BAU%5D+AND+photodynamic.
(2) The structures and functions of fibrinolytic proteins, including urokinase (uPA), its receptor (uPAR), inhibitor (PAI-1), and tPA. We determined the crystal structures of uPAR:uPA, uPA:peptide, tPA:PAI-1 and uPA:PAI-1 complexes. PAI-1 and uPA are biomarkers for cancer metastasis. We developed inhibitors for PAI-1 (small molecule, Embelin, and protein-based, named PAItrap), and for uPA (cyclic peptides), and discovered new principles for inhibitor development. We also developed inhibitors for uPAR, and one inhibitor (ATF) was fused to human serum albumin (HSA) to increase plasma half-life, and to render drug carrier properties of the fusion protein. For a list of publications, see https://www.ncbi.nlm.nih.gov/pubmed/?term=Huang%2CMingdong%5BAU%5D+AND+(urokinase+OR+PAI-1) .
(3) Crystal structures of cell surface receptors and albumin. HSA is an actively studied protein due to its wide applications. We determined a series of crystal structures of HSA. A surprising finding is the conversion of glucose from cyclic form to linear form induced by HSA, suggestion a new function for this old protein. For a list of publications, see https://www.ncbi.nlm.nih.gov/pubmed/?term=Huang%2CMingdong%5BAU%5D+AND+albumin
National and International Profile: Dr. Huang has delivered invited presentations in many international conferences and institutions. He was also an International Visiting Professor funded by Aarhus University in 2004. Since 2010 Dr. Huang organized three international meetings: (1) 7th Scientific Meeting of Danish-Chinese Centre for Proteases and Cancer, Soochow, China, February 22nd-25th, 2011. (2) Novo Nordisk - Chinese Academy of Science (CAS) workshop on Serine Protease Enzyme Systems in Health and Disease, Guilin, Guangxi, October 26th-30th, 2013. (3) 8th International Symposium on SERPINs and Proteases in Health and Disease, Shanghai, China, March 23rd-27th, 2017
International collaborations: Dr. Huang has established a number of international collaboration with investigators at United States, France, Australia, and Denmark. He established Danish-Chinese Centre of Proteases and Cancer (2008-2016), together with Prof. Peter Andreasen of Aarhus University, and five other research groups of Denmark. This centre was funded by both Chinese and Danish governments (grant numbers 31161130356 and 30811130467).
Awards and achievements: Dr. Huang was the recipient of Chinese National Distinguished Investigator award (2006). He has published 200 research articles (see e.g., https://www.ncbi.nlm.nih.gov/pubmed/?term=Huang%2CMingdong%5BAU%5D+OR+Huang%2CMing-Dong%5BAU%5D), 3 books, and held more than a dozen patents. One of the patents was commercialized in 2012. In his career, he has trained 6 post-doctoral fellows and more than 30 PhD or MS students, three of them are now full professors.
Supervision and Mentoring: Dr. Huang established a biology PhD training program in the FJIRSM institute of Chinese Academy of Sciences. His laboratory also accommodated the visits of many domestic and international postdocs and scholars. For current group members, see http://fmerc.fzu.edu.cn/html/rcdw/hmdktz/1.html.
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