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).
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 and hopefully this award will help she secure an independent faculty position!
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 !