Molecular Medicine 2014
Undergraduate Institute: Johns Hopkins University
Research Advisor: Toni Antalis, Ph.D.
Current Position: Senior Associate, Center for Strategic Philanthropy at Milken Institute
Description of Research
Our lab studies the biology of serine proteases and serine protease inhibitors (SERPINs) in several cell types. Functionally, our lab investigates how the dysregulation of these enzymes contributes to immunomodulation and the pathophysiology of membrane barrier integrity, angiogenesis, and cancer. Currently, I am investigating the molecular mechanisms that govern macrophage survival. Specifically, I am looking at how lipopolysaccharide, a bacterial endotoxin, regulates the transcription of plasminogen activator inhibitor type 2 gene (PAI-2). PAI-2, also known as SERPINB2, has been implicated in mediating a cytoprotective effect on macrophages.
PAI-2, originally identified as a physiological inhibitor of urokinase-type plasminogen activator (uPA), is unique in that it exists predominantly as an intracellular glycosylated protein mediating several intracellular events independent of uPA inhibition. Our data provide evidence of a gene-regulatory network that works to achieve maximal activation of PAI-2 in macrophages. It is crucial for macrophages to subvert cell death because they are the main effectors of our innate immune system, and they play a role in establishing immunological memory through the adaptive immune response. Bacterial infections, such as M. tuberculosis, threaten the world’s population, and many such pathogens mediate their effects by causing macrophage cell death, and overcoming the host’s defenses. In the same vein, B. anthrasis, a biological weapon, also mediates its effects by shutting down protective mechanisms within the macrophage, thus leading to cell death. Therefore, my research could potentially have broad implications in mediating pathogen clearance, septic shock and tissue repair.