About Me
In a broader context, my work has revealed how intrinsic flexibility endows β2 integrins with an ability to
recognize ligands at a range of distances and rotation, which would be important during rolling of leukocytes, a process
that precedes firm adhesion and transmigration across the activated vascular endothelium. However, engagement of
integrin to its ligand could then substantially reduce integrin flexibility on the endothelium. This would enable the
integrin-ligand complex to resist the distorting effects of fluid stress forces and facilitate the cellular traction required for
leukocyte migration.
In a collaborative effort with the laboratories of Drs. Tanya Mayadas and Cheng Zhu, I studied a polymorphic variant of the Mac-1 (αMβ2) integrin, which is highly associated with, Systemic Lupus Erythematosus (SLE), an autoimmune disease. This variant exhibited a marked impairment in affinity maturation of Mac-1 integrin under shear- flow and the ability to form catch bonds.
Prior to my work, biochemical and structural studies for the intact type-II integrins were unsuccessful due to their low expression, heterogeneity in solution and promiscuity. I have developed a customized expression system for integrins, which indeed also helped crystallization of other integrins, αVβ3, α5β1, αVβ6 and αVβ8 in the field and is widely used. Using my system, I collaborated with GSK and engineered ectodomains of αXβ2 and αLβ2 integrins in the closed state, which, in turn, offered rigid scaffolds for antagonist and agonist design. In parallel, I developed an inhibition assay to demonstrate the efficacy of individual small molecule antagonist hits on integrin-ligand interactions.
Academic Appointments
Assistant Professor |
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Instructor |
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Postdoctoral Fellow |
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Graduate Student |
Education
Biochemistry & Structural Biology, PhD |
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Chemistry, BS Molecular Biology & Genetics, BS |
Contact
| SERC Building, Suite 4012 | |
| msen@uh.edu | |
| +1 713 743-1448 |