Eskandarian Haig A

My research has focused on studying general mechanisms of microbial pathogenesis. During my doctoral thesis work, I focused on understanding how microbial pathogenesis by Listeria monocytogenes, is characterized by a global hijacking of host cell processes. We focused on discovering how the pathogen induces host chromatin-modifications leading to changes in global gene transcription. For my postdoctoral work, I had the good fortune of receiving four years of funding through an EMBO long-term fellowship and an EMBO advanced long-term fellowship, for which less than one percent of applicants were awarded both. Working simultaneously in engineering and microbiology labs, this interdisciplinary environment enabled me to develop and utilize a novel single-cell microscopy technique, called Long-Term Time-Lapse Atomic Force Microscopy (LTTL-AFM) [3]. I sought to discover the mechanisms enabling mycobacterial pathogens to resist antibiotics and host immunity by studying critical fundamental cell processes for which no molecular mechanisms are yet known. My efforts have aimed at precisely defining the molecular and mechanical principles controlling mycobacterial division, growth and death. My initial work culminated in the publication of a seminal work on how division site selection (DSS) is programmed in mycobacteria, which lack all known molecular determinants of DSS described in other bacteria, albeit evolutionarily disparate [4]. We now have a conceptual framework by which to understand how molecular determinants might drive DSS in mycobacteria. My work has also focused on pioneering and advising students to reveal the interplay in mechanical and molecular determinants working in unison to drive mycobacterial cell cleavage and pole growth dynamics [1 & 2], both of which are believed to influence antibiotic tolerance. In an effort to discover how mycobacteria undergo cell death, I sought to stress individuals by both macrophage infection and antibiotic treatment. These efforts have led to the serendipitous discovery that mycobacteria physically adapt to stress and this adaptation represents a critical step in the logic of how resistance is programmed. Having recently moved from EPFL to UCSF, I am now ideally poised to discover the molecular determinants underlying how mycobacteria adapt to stress, both mechanical and biochemical. Additionally, the Division of Experimental Medicine offers an unique location to harness the expertise of colleagues in immunology and to envisage translating the fundamental cell processes that I discover to more translational and clinical environments.