Scholar Profile

Sarah A. Stanley

Assistant Professor
Division of Infectious Disease and Vaccinology
School of Public Health
University of California, Berkeley
500C Li Ka Shing
MC3370
Berkeley, CA 94703
Voice: 510-666-3729
Email: sastanley@berkeley.edu
Personal Homepage
2014 Searle Scholar

Research Interests

Mycobacterium tuberculosis: a Remarkably Successful Pathogen

Mycobacterium tuberculosis is estimated to infect 2 billion people, or almost one-third of the world’s population. The majority of infections are latent, meaning that the immune system is able to contain, but not eliminate infection. Active disease results when immune defenses wane and bacteria are able to actively replicate. The cellular and molecular factors that determine whether disease is latent or becomes active are poorly understood. M. tuberculosis is a pathogen of macrophages, cells that normally function to kill invading microbes. On one level the outcome of M. tuberculosis infection is determined by the macrophage’s ability to mount microbicidal responses balanced by the bacterium’s ability to resist these processes and acquire nutrients necessary for sustaining growth and survival.

Metabolic regulation of M. tuberculosis infection

Our work is motivated by the idea that host-cell metabolism is at the heart of the M. tuberculosis-macrophage interaction. M. tuberculosis must acquire all of its nutrients required for survival from the host cell, and macrophage metabolism dictates the types of nutrients available to the bacterium. Moreover, macrophages are remarkably plastic cells that can take on a range of differentiated effector states. There is emerging awareness that specific metabolic pathways underlie different programs of macrophage differentiation, gene expression, and effector function, and specific alterations in metabolism dictate the range of microbicidal functions that can be employed against a particular microbe. Understanding the metabolism of macrophages has important consequences for understanding the survival of pathogens such as Mycobacterium tuberculosis that exploit macrophages as a host cell. Our goal is to elucidate connections between macrophage metabolism, effector functions that are specifically relevant to M. tuberculosis infection, and nutrient availability. In addition, we hope to uncover ways in which M. tuberculosis manipulates macrophage metabolism to facilitate intracellular survival. To do so we employ a diverse toolkit encompassing host and bacterial genetics, chemical biology, imaging, and global transcriptional and metabolite profiling. This work will shed light on the complex interplay between the host and the pathogen during a latent infection, and may also suggest new avenues for the development of novel therapeutics for treating M. tuberculosis.