Amy Barczak

Amy Barczak

Assistant Professor of Medicine
Amy Barczak
Work in the Barczak lab focuses on the molecular pathogenesis of Mycobacterium tuberculosis. After COVID-19, tuberculosis is the leading cause of death from infection globally. A comprehensive understanding of the cellular and molecular events that drive Mtb’s success as a pathogen remains elusive. Using cellular and mouse models of TB infection, we explore how Mtb virulence factors interact with host factors to shape infection outcomes. Macrophages are the first cells that take up Mtb. Although one key role of macrophages is recognizing and responding to invading microbes, Mtb is able to survive and grow in at least a subset of infected cells. The capacity to damage the phagosomal membrane has emerged as a key function of virulent mycobacteria; this damage is postulated to benefit the bacterium in the host-pathogen standoff. Current areas of interest in the lab include (1) defining the consequences of phagosomal membrane damage for the innate immune responses to Mtb and (2) identifying host factors that constrain or repair phagosomal membrane damage.
 
The lab also has a significant interest in how extracellular matrix (ECM) remodeling contributes to tuberculosis pathogenesis. Most studies of microbial pathogenesis focus exclusively on the interactions between microbes and host cells; the ECM is generally considered to be an inert scaffold. However, matrix damage and remodeling are an inherent part of the tissue damage that occurs during the progression of multiple pathologic processes, including TB infection. Early active TB is characterized by
exponential bacterial growth; immune cell recruitment and the development of infiltrative lung lesions follow, driving a plateau in bacterial number. We are interested in how individual matrix enzymes contribute to inflammation, tissue damage, and cellular infiltration in this early stage of TB disease. In later stages of infection, acute tissue damage gives way to overly exuberant ECM remodeling, with resulting fibrosis and permanent lung damage. We are interested in identifying the ECM remodeling enzymes that contribute to pathologic remodeling and fibrosis in later stages of TB infection.

Contact Information

Ragon Institute of MGH, MIT and Harvard
400 Technology Square, Room 990
Cambridge, MA 02139

Community or Program Affiliation

People