Jennifer Philips, MD, PhD
Assistant Professor, Departments of Medicine, Pathology, and Microbiology
Smilow Research Building
550 First Avenue
New York, NY 10016
Email: Jennifer Philips
|Medical Education:||2000, MD from the University of California, San Francisco|
|Graduate Education:||1998, PhD from the University of California, San Francisco|
|Postdoctoral Training:||2002-2006 Harvard Medical School|
|Academic Appointments:||2009, Assistant Professor, NYU
2006, Clinical Instructor, Harvard Medical School
|Academic Responsibilities:||Course Co-director, CMB Special Topics Course: Principles of Protein Modifications in Health and Disease; Member, Medical Scientist Training Program Faculty Operating Committee|
|Major Honors:||2008 — Maxwell Finland Award for Excellence in Research
Massachusetts Infectious Disease Society
2009 — Michael Saperstein Medical Scholar, NYU, Dept of Medicine
2010 — Clinical Scientist Development Award, Doris Duke Charitable Foundation
2010 — Astellas Young Investigator Award, Infectious Disease Society of America
2011 — Edward Mallinckrodt Jr. Foundation Award
2013 — Colton Scholar
Approximately one-third of the world’s population is infected with Mycobacterium tuberculosis (Mtb), the causative agent of the disease tuberculosis. Mtb is able to establish this enormous worldwide burden of disease by disrupting the anti-microbial pathways of the macrophage, allowing the bacilli to survive for decades in immunologically normal hosts.
An important virulence property of Mtb is its ability to avoid delivery to the lysosome. The Mtb-induced block in phagosome-lysosome fusion has been attributed to a wide array of lipid and protein effectors, but the mechanism remains poorly understood. Specialized secretion systems are often used by bacterial pathogens to translocate effectors that target the host, and Mtb encodes type VII secretion systems (TSSSs) that enable mycobacteria to secrete proteins across their complex cell envelope.
We found that EsxH, which is secreted by the Esx-3 TSSS, interacts with the host protein Hgs/Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate), a component of the endosomal sorting complex required for transport (ESCRT). ESCRT is required to deliver Mtb to the lysosome and to restrict intracellular bacterial growth. The Mtb effector, EsxH, in complex with EsxG, disrupts ESCRT function and impairs phagosome maturation.
Thus, we demonstrated a role for a TSSS and the host ESCRT machinery in one of the central features of tuberculosis pathogenesis. Ongoing work in the laboratory involves further elucidating the importance of EsxH and ESCRT in mycobacterial pathogenesis. In addition, work of others has demonstrated the importance of autophagy in resistance to Mtb.
Additional projects in the laboratory involve defining the molecular basis by which the autophagy machinery recognizes mycobacteria. The work in our laboratory is motivated by the medical importance of TB, enormous gaps in the understanding of the interaction between the bacteria and host macrophages, and the fact that novel technologies offer new ways to fill those gaps.
|Alka Mehra, PhD
|Stefan Koster, PhD
|Cynthia Portal, MD, PhD
|Name||Term||Present or last known position|
|Aleena Zahra (technician)||2009-2013||Medical student, NYU School of Medicine|
|Kristen Penberthy (technician)||2009-2010||MD-PhD student, University of Virginia School of Medicine|
|Ashley Wells (technician)||2009-2010||Medical student, Mt. Sinai School of Medicine|