Pharmacological targeting heparan sulfate–protein interactions
While understanding novel physiological functions of heparan sulfate is always thrilling, finding ways to manipulate its functions in pathological conditions can be life-saving. Heparin, a highly sulfated form of heparan sulfate made by mast cells, has been widely used as a potent anticoagulant for over a century. Heparin works by promoting the inhibition of antithrombin towards thrombin, which drives blood coagulation. We envision that the functions of many more disease-causing HS-binding proteins can be modulated by manipulating their interactions with HS. We believe the interactions can be manipulated in two different ways. The first approach is to utilize structure-defined HS oligosaccharides or HS mimetic, which would function as antagonists or agonists to inhibit or promote the interactions between HS and HS-binding proteins. The second approach is to target the HS-binding sites of HS-binding proteins by mAbs, which would effectively antagonize their interaction with HS and block their function.
Currently, we are working with Dr. Jian Liu's group to inhibit the activity of HMGB1 using the first approach. We are also developing mAbs to inhibit RAGE activation using the second approach.
Patents:
-
U.S. provisional patent application (No. 62/928,884) was filed on October 31, 2019. The application describes an anti-RAGE mAb that we developed, which inhibits HS-dependent RAGE oligomerization and RAGE signaling. Role: Principle inventor.
-
U.S. Provisional Patent Application (No. 62/581,443). The application describes an structure-defined HS oligosaccharides that displays protective effect on drug-induced liver damage. Role: co-inventor (principle inventor: Dr. Jian Liu).
Pharmacological targeting heparan sulfate–protein interactions
While understanding novel physiological functions of heparan sulfate is always thrilling, finding ways to manipulate its functions in pathological conditions can be life-saving. Heparin, a highly sulfated form of heparan sulfate made by mast cells, has been widely used as a potent anticoagulant for over a century. Heparin works by promoting the inhibition of antithrombin towards thrombin, which drives blood coagulation. We envision that the functions of many more disease-causing HS-binding proteins can be modulated by manipulating their interactions with HS. We believe the interactions can be manipulated in two different ways. The first approach is to utilize structure-defined HS oligosaccharides or HS mimetic, which would function as antagonists or agonists to inhibit or promote the interactions between HS and HS-binding proteins. The second approach is to target the HS-binding sites of HS-binding proteins by mAbs, which would effectively antagonize their interaction with HS and block their function.
Currently, we are working with Dr. Jian Liu's group to inhibit the activity of HMGB1 using the first approach. We are also developing mAbs to inhibit RAGE activation using the second approach.
Patents:
-
U.S. provisional patent application (No. 62/928,884) was filed on October 31, 2019. The application describes an anti-RAGE mAb that we developed, which inhibits HS-dependent RAGE oligomerization and RAGE signaling. Role: Principle inventor.
-
U.S. Provisional Patent Application (No. 62/581,443). The application describes an structure-defined HS oligosaccharides that displays protective effect on drug-induced liver damage. Role: co-inventor (principle inventor: Dr. Jian Liu).
Ding Xu, PhD
Associate Professor
Dr. Xu has been studying heparan sulfate his whole scientific career. He was highly fortunate to be mentored by two leading experts in heparan sulfate biology. With Dr. Jian Liu at UNC Chapel Hill, he studied biosynthetic enzymes of heparan sulfate and became an expert in HS structure, HS biosynthesis, protein expression and purification, and structural biology. With Dr. Jeff Esko at UCSD, he studied the physiological roles of heparan sulfate in vascular biology, inflammation and infection, during which time he became an expert in cell biology and animal models of human diseases. In 2014, Dr. Xu moved to the University at Buffalo to established his own lab with a new direction to study the role of HS in bone remodeling. Benefitted from his diverse training background, the type of study his lab is conducting is highly multidisciplinary, often spans structural biology, biochemistry, cell biology, genetically modified murine models and development of therapeutics.
Education
1995 - 1999
Central China Normal University
BS in Biochemistry
2002 - 2006
University of North Carolina at Chapel Hill
School of Pharmacy
PhD in Pharmaceutical Sciences
2007 - 2011
University of California, San Diego
Department of Cellular and Molecular Medicine
School of Medicine
Postdoctoral fellow
2011 - 2014
University of California, San Diego
Department of Cellular and Molecular Medicine
School of Medicine
Staff Scientist
2014 - 2019
University at Buffalo, SUNY
Department of Oral Biology
School of Dental Medicine
Assistant professor
Email: dingxu@buffalo.edu
Tel: 716-829-3509
Education
Miaomiao Li, PhD
Research Scientist
2005 - 2009
Shandong University of Traditional Chinese Medicine
BS in Pharmacy
2009 - 2015
Ocean University of China
School of Pharmacy
PhD in Pharmaceutical Sciences
Projects:
HS–SOST interactions in Bone remodeling
2015 - 2020
University at Buffalo
Department of Oral Biology
Postdoctoral Scholar
Email: mli55@buffalo.edu
Chih-Yean Ong
PhD student (2018)
Projects:
Role of HS in regulating osteoblast differentiation
Development of anti-RAGE mAb
Education
2009 - 2013
International Medical University, Malaysia
BS in Pharmaceutical Chemistry
2013 - 2018
Quality control management in various pharmaceutical companies in Malaysia and Singapore.
Email: chihyean@buffalo.edu
Yin Luo
PhD student (2019)
Education
Projects:
Role of HS in Cathepsin K biology
Roel of HS in TRAIL-induced apoptosis
2011 - 2016
Central South University
Xiangya School of Stomatology
BS in Stomatology
2016 - 2019
Central South University
Xiangya School of Stomatology
MS in Endodontics
Email: yinluo@buffalo.edu
Huanmeng Hao
PhD student (2021)
Projects:
Projects:
Role of HS in Cathepsin K biology
Role of HS in Odontoblast biology
HS-IFN-beta interaction in osteoclastogenesis
Education
2013 - 2018
Xi'an Jiao Tong University
School of Stomatology
BS in Stomatology
2018- 2021
Xi'an Jiao Tong University
School of Stomatology
MS in Stomatology
Email: huanmeng@buffalo.edu
Ziling Chen
PhD student (2023)
Projects:
Role of HS in osteoblast differentiation
Targeting RAGE in rheumatoid arthritis
Education
2013 - 2018
Xi'an Medical University
BS in Stomatology
2019- 2022
Xi'an Jiao Tong University
School of Stomatology
MS in Stomatology
Email: zilingch@buffalo.edu
Lab alumni
Xiaoxiao Zhang
PhD student (2016-2021)
Education
2006 - 2012
Shanghai Jiao Tong University
School of Medicine &Stomatology
BS in Stomatology
2012 - 2014
Shanghai Jiao Tong University
School of Medicine &Stomatology
MS in Oral and Maxillofacial Implantology
Current position:
Postdoctoral researcher at Eli Lilly