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).
09-14-2026
Huanmeng's PhD defense day!!
09-01-2026
Warm welcome to Dr. Xiaoxiao Zhang, who rejoined the lab as a Research Scientist. Dr. Zhang spend the last 5 years as a scientist focusing on mAb development at Eli Lilly and Charles River Laboratories. So great to have her back to lead several projects in mAb development and drug delivery!
08-11-2026
Warm welcome to Dr. Dongfang Li, who just jointed the lab as a Research Scientist. Dr. Li spend the last 5 years as a postdoc scholar at ADA Forsyth Institute/Harvard School of Dental Medicine and will bring a wealth of experience in cell biology and animal disease models to the group!
07-02-2026
Dr. Xu was elected as a vice chair for 2028 Gordon Research Conference (GRC)–Proteoglycans. GRC–Proteoglycans is the premier conference in our field and it is such a great honor to be elected to service our great community in 2028 (as vice chair) and 2030 (as co-chair) GRCs.
05-06-2026
Our third Cathepsin K paper describing the structural insight of HS-mediated proCtsK activation is published on Biochemical Journal today! Congratulations to Huanmeng!
04-22-2026
Our second Cathepsin K paper describing the bone phenotype of HS-binding deficient CtsK knockin mice is published on Matrix Biology today! Congratulations to Yin, Xiaoxiao and Huanmeng!
07-23-2024
After a blessed 10 years at the University at Buffalo, the lab will move to Emory University to start our new journey in the newly established Musculoskeletal Research Center, furthering our study of heparan sulfate in bone and cartilage diseases!
07-02-2024
Chihyean successfully defended his thesis today, becoming the third PhD out of Xu lab. Congratulations!
05-01-2024
Our first Cathepsin K paper is published on Matrix Biology today! Congratulations to Xiaoxiao, Yin and Huanmeng!
04-22-2024
Yin successfully defended her thesis today, becoming the second PhD out of Xu lab. Congratulations!
04-12-2024
Huge congratulations to Miaomiao for accepting a tenure-track Assistant Professor position at the College of Dentistry, Ohio State University !!!
01-04-2024
Chihyean's anti-RAGE mAb paper was published on Glycobiology today! Congratulations!
11-01-2023
Yin and Huanmeng's TRAIL-HS paper was published on eLife today! Congratulations!
09-01-2023
In collaboration with Dr. Baohong Zhao (PI), our labs are awarded with a 5-year R01 grant from NIAMS to study the role of Heparan sulfate in inflammatory bone remodeling!
02-01-2023
Congratulations to Miaomiao for receiving her NIDCR R03 award for Young Investigators!!
07-15-2022
Both Miaomiao and Yin were selected to give oral presentations in 2022 Gordon Proteoglycan conference! They have both done excellent jobs presenting and really showcased the diverse subjects we study in the lab!
07-14-2022
Our lab is awarded with a new 5-year R01 grant from NIDCR to study the role of Heparan sulfate–cathepsin K interaction in bone remodeling !
07-02-2022
Miaomiao scored an excellent priority score of 23 in her resubmission of NIDCR R03 award for Young Investigators. Really proud of her!
02-01-2022
Miaomiao's RAGE paper is officially accepted by eLife today! This is our third paper on RAGE since 2011. By using a novel RAGE knock-in strain and an mAb that specifically target the HS-binding site, we demonstrated that HS-induced oligomerization is essential for RAGE signaling in vivo.
08-04-2021
Xiaoxiao successfully defended her thesis today, becoming the first PhD out of Xu lab. Congratulations!
01-20-2021
Xiaoxiao's cystatin C paper was officially accepted by Communication Biology today! Another prime example of the structural diversity of HS-binding site.
07-08-2020
Miaomiao's OPG knockin mice paper appeared online today on PNAS website! This is our third paper on OPG and first knock-in animal with impaired HS-binding site.
06-18-2020
We have completed moving the lab to a new space in Biomedical Research Building. A refreshing change after a long dormancy during COVID19!
06-02-2020
We were awarded $90,000 by Buffalo Accelerator Funds to develop our anti-RAGE mAb for treatment of inflammatory diseases !