Susanta Sarkar

Matrix metalloproteases (MMPs), a 23-member family of human enzymes, are crucial for human health because they directly or indirectly affect most of the top ten causes of death in the USA. Despite their importance, targeting MMPs for improving human health is challenging because MMPs have diverse functions and interact with and degrade many proteins in the human body. Any drug targeting the active site of MMPs inhibits intended as well as unintended functions and results in adverse side effects. My primary research goal is to control one function of a protein without altering its other functions. 

Although we are interested in the fundamental understanding of protein function, we hope to improve human health through research because we get funding from the National Institutes of Health (NIH). My current focus is on MMP1 (interacts in the extracellular environment) and MMP14 (anchored to the cell membrane), both of which degrade collagen and are essential for normal tissue remodeling and cancer metastasis.

We take an integrative approach to studying water-soluble MMPs interacting with water-insoluble substrates. Many physiologically important substrates are water-insoluble, such as collagen fibrils (cancer metastasis), crosslinked fibrin (the primary component of a blood clot), and aggregates of proteins such as alpha-synuclein and amyloid-beta (involved in Parkinson’s and Alzheimer’s). There are not many techniques to investigate molecular understanding of enzyme activity on insoluble substrates. We validate simulated dynamics using experimental dynamics at the single molecule level. Please check out some of our publications below.