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:
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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.
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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. In 2024, Dr. Xu moved to his current position in the Department of Orthopaedics at Emory University.
Education and Experience
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 - 2024
University at Buffalo, SUNY
Department of Oral Biology
School of Dental Medicine
Assistant Professor (2014-2019)
Associate Professor (2020-2024)
2024 - present
Emory University
Department of Orthopaedics
Department of Biochemistry
School of Medicine
Associate Professor
Email: ding.xu@emory.edu
Tel:
Xiaoxiao Zhang
Research Scientist
Projects:
mAb development for treating musculoskeletal diseases
Cartilage delivery
Role of HS in Cathepsin K biology
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
2016 - 2021
University at Buffalo, SUNY
School of Dental Medicine
PhD in Oral Biology
Dongfang Li
Research Scientist
Education
2010 - 2017
Shandong University
School of Stomatology
BS and MS in Dental Science
2017 - 2021
Shanghai Jiao Tong University
School of Stomatology
DDS and PhD in Dental Science
Projects:
HS-MMP13 interaction in musculoskeletal diseases
HS-MMP14 interaction in musculoskeletal diseases
Huanmeng Hao
PhD student (2021)
Projects:
Role of HS in Cathepsin K biology
HS-IFN-beta interaction in osteoclastogenesis
HS-MMP interactions
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.hao@emory.edu
Jenny Lin
Lead Research Specialist
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Education
2016 - 2020
National Chung Hsing University
BS in Food Science and Biotechnology
2020- 2024
University of Georgia
MS in Nutritional Sciences
Email: yu-chen.lin@emory.edu
Projects:
HS in MMP biology
mAb development
Yu Bai
Lead Research Specialist
Education
2010 - 2015
Changzhi Medical College
MD
Email: yu.bai2@emory.edu
Projects:
Targeting RAGE in rheumatoid arthritis
Cartilage delivery
Christopher Park
Emory undergraduate
Education
2025 - present
Emory University
Department of Chemistry
Email: christopher.park2@emory.edu
Projects:
HS in MMP biology
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:
Research Scientist
Emory University
Education
Miaomiao Li, PhD
Postdoc and Research Scientist (2015-2024)
2005 - 2009
Shandong University of Traditional Chinese Medicine
BS in Pharmacy
2009 - 2015
Ocean University of China
School of Pharmacy
PhD in Pharmaceutical Sciences
Email: li.15541@osu.edu
Current position:
Assistant Professor
College of Dentistry, Ohio State University
Chih-Yean Ong
PhD student (2018-2024)
Current position:
Postdoctoral scholar
Roswell Park Cancer Institute, Buffalo, NY
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 (2019-2024)
Education
Current position:
Postdoctoral scholar
Forsyth Institute, Boston MA
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
Daniel Tehrani
Education
Post Doctoral Scholar (2025-2026)
2015 - 2019
Georgia State University
BS in Biology
2020- 2025
University of Georgia
PhD in Biochemistry and Molecular Biology
Current position: