The School of Natural Sciences
At the Crossroads of Drug Discovery and Understanding Basic Mycobacteriology
Landys Lopez Quezada, Ph.D.
Department of Microbiology and Immunology/Department of Natural Sciences
Weill Cornell Medicine/Marymount Manhattan College
Friday, June 11th, 2021
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Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is attributed to over 1.5 million deaths in 2016 and is estimated to infect a third of the global population. With treatment requiring prolonged exposure to several classes of antibiotics and resistant strains becoming more prevalent, the need for novel treatment strategies is urgent. While studying the mechanism(s) of action of two families of small molecules, we were left with several mysteries. The b-lactam family of antibiotics proved surprisingly effective against replicating and dormant Mtb cells. What are the mediators of b-lactam induced cell lysis? Two component signal transduction systems are the most likely mediators. 4-hydroxyquinolines, the second family of antimycobacterial compounds, induced a catastrophic loss of Mg2+ in mycobacterial cells, overwhelming the homeostatic capacity of the two principle Mg2+ transporters, CorA and MgtE. Because metallo-homeostasis depends on a careful balance of metal concentrations, I hypothesized that Mg2+ homeostasis represents a novel vulnerability in Mtb that has yet to be exploited and CorA, a proven druggable target whose cellular role and regulation is not well understood, holds the key to that vulnerability.
My scientific career spans many facets of infectious disease biology. I completed my doctoral research on Schistosoma mansoni under Dr. James McKerrow at the University of California, San Francisco. During my tenure at UCSF, I was a National Institute of General Medical Sciences Fellow and a Microbial Pathogenesis and Host Defense Research Fellow. After my graduate studies, I joined Dr. Carl Nathan’s Laboratory at Weill Cornell Medicine (WCM) where I investigated the mechanism of action and resistance of novel antimycobacterials uncovered during our small molecule screening campaigns searching for novel chemical scaffolds that kill Mycobacterium tuberculosis (Mtb). As an Instructor at WCM, I developed an in vitro model of human tuberculous caseum. Additionally, for the past two years I have been teaching at Marymount Manhattan College as an Adjunct Professor.
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