Sriram Neelamegham

PhD

Sriram Neelamegham

PhD

Sriram Neelamegham

PhD

Research Topics

Biomedical engineering; cell biomechanics; vascular engineering

Contact Information

906 Furnas Hall

Buffalo NY, 14260

Phone: (716) 645-1200

Fax: (716) 645-3822

neel@buffalo.edu

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Research Interests

My laboratory performs investigations in the fields of Molecular & Cellular Bioengineering, Systems Glycobiology, and Thrombosis & Hemostasis. In particular, we are interested in applying quantitative experimental and computational techniques to discover new mechanisms that control the cell adhesion properties of blood leukocytes and platelets during human inflammatory and thrombotic disorders. Many of the projects in my laboratory assess the roles of fluid/hydrodynamic forces, biochemical reaction networks and cell adhesion molecule binding properties on blood cell adhesion mechanics during inflammation, thrombosis & hemostasis, and cancer. A long term goal is to apply our knowledge of these regulatory pathways to identify new targets for drug development.

Our studies of inflammation biology examine the contribution of cell surface carbohydrate structures or glycans to white blood cell (leukocyte) activation and adhesion. In this regard, while glycosylation is a major post-translational modification (PTM) that alters the structure of most human proteins, relatively little is known about the functional diversity imparted by this modification. Unlike other PTMs like phosphorylation which are single step events, glycan biosynthesis is more complex since it involves the concerted action of a family of ~200 enzymes called glycosyltransferases (1% of the human genome). In my laboratory, we have developed numerous experimental tools to examine glycosylation at the molecular, cellular and animal levels. Principles of chemical reaction kinetics are used to model glycosylation reaction networks. The end goal is to apply systems level understanding of glycosylation processes in order to uncover new pathways and small molecule inhibitors that can control leukocyte migration during inflammation. This project also aims to develop cutting-edge experimental tools and theoretical concepts for studies in the emerging field of “Systems Glycobiology”.

Read more about the Neelamegham group's research

Other studies in my laboratory focus on von Willebrand Factor (VWF) structure-function relationships. This study is clinically significant since the recruitment of blood platelets by immobilized VWF at sites of vascular injury is an important contributor to arterial occlusion during myocardial infarction (heart attack) and stroke. In particular, we are interested in understanding how fluid shear and surface immobilization alters the three-dimensional structure of VWF thus promoting both protein conformation change and VWF self-association. In this regard, the former alteration affects the affinity of platelet-VWF interaction. The latter affects the avidity of this molecular binding event. While hypotheses related to this project are typically generated using computational models and in vitro experiments, we typically also validate these hypotheses using animal models and human blood samples from normal and disease individuals.

Projects

10/11/17
Identifying new technologies to improve stem cell therapy for an array of cardiovascular diseases. 

Sriram Neelamegham in the news