Sriram Krishnaswamy studies the molecular mechanisms underlying blood coagulation. His laboratory investigates how proteins involved in blood coagulation interact with membranes to yield regulated clotting responses to vascular injury and to understand the unregulated responses seen in thrombotic and bleeding diseases. The regulation of blood coagulation response to vascular injury is essential for life, as excessive bleeding is associated with a range of genetic and acquired conditions that impair the clotting response. Conversely, thrombotic diseases result from dysregulated clotting. Together, these diseases represent major causes of morbidity and mortality in the developed world. Dr. Krishnaswamy's research focuses on the proteolytic activation steps in coagulation, which are catalyzed by membrane complexes assembled through reversible binding of serine protease protein cofactors to the membrane surface. His lab employs a combination of biophysical techniques, mutagenesis, and functional studies to relate the binding steps to significant increases in the function of serine protease biological substrates. The team also investigates how substrates are recognized by enzyme complexes and how substrate cleavage imparts biological activity to the products. By using advanced techniques like X-ray crystallography and cryo-electron microscopy, they provide structural insights into the interactions of components relevant to function, aiming to reveal novel strategies to modulate coagulation reactions for disease treatment.