Dr. Oren Rosenberg is an infectious disease physician with a background in structural biology. His objective in this current project is to combine his clinical and basic science interests by studying the structure and function of key virulence determinants in Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. Through a series of specific aims that use a combined structural, biochemical and genetic approach, Dr. Rosenberg will examine the role of essential components in the type VII secretion system, which is known to be critical for the virulence of Mtb. The goal is to understand mycobacterial infection better so as to aid in the design of faster, cheaper, less toxic and more effective ways to prevent and treat tuberculosis. Additionally this proposal is designed to complement Dr. Rosenberg's prior laboratory experience and provide him with the requisite technical and intellectual background in microbial pathogenesis and structural biology to function as an independent investigator. A committee of physicians and scientists will oversee Dr. Rosenberg's progression towards independence. His scientific development will also be enriched through attendance at UCSF courses in pertinent topics, several seminar series, departmental retreats and national meetings. Dr. Rosenberg will develop a clinical specialization in tuberculosis and other respiratory infections through work at the tuberculosis clinic at San Francisco General Hospital. At the end of the granting period Dr. Rosenberg will be prepared to develop his own research and clinical agenda as an independent investigator in the basic biology of microbial pathogenesis.

Public Health Relevance

Tuberculosis is a global problem leading to over 1.7 million deaths each year. The proposed work is relevant to determining how the bacteria that cause tuberculosis are able to establish and maintain infection in a human host. Understanding this process at an atomic level will help us to design targeted therapies and vaccines.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Clinical Investigator Award (CIA) (K08)
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Microbiology and Infectious Diseases B Subcommittee (MID)
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Jacobs, Gail G
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University of California San Francisco
Internal Medicine/Medicine
Schools of Medicine
San Francisco
United States
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Rosenberg, Oren S; Dovala, Dustin; Li, Xueming et al. (2015) Substrates Control Multimerization and Activation of the Multi-Domain ATPase Motor of Type VII Secretion. Cell 161:501-512
Mirrashidi, Kathleen M; Elwell, Cherilyn A; Verschueren, Erik et al. (2015) Global Mapping of the Inc-Human Interactome Reveals that Retromer Restricts Chlamydia Infection. Cell Host Microbe 18:109-21
Hadjivassiliou, Haralambos; Rosenberg, Oren S; Guthrie, Christine (2014) The crystal structure of S. cerevisiae Sad1, a catalytically inactive deubiquitinase that is broadly required for pre-mRNA splicing. RNA 20:656-69
Lohse, Matthew B; Rosenberg, Oren S; Cox, Jeffery S et al. (2014) Structure of a new DNA-binding domain which regulates pathogenesis in a wide variety of fungi. Proc Natl Acad Sci U S A 111:10404-10
Scharschmidt, Tiffany C; Amerson, Erin H; Rosenberg, Oren S et al. (2013) Immune reconstitution reactions in human immunodeficiency virus-negative patients: report of a case and review of the literature. JAMA Dermatol 149:74-8
Rosenberg, Oren S; Dovey, Cole; Tempesta, Michael et al. (2011) EspR, a key regulator of Mycobacterium tuberculosis virulence, adopts a unique dimeric structure among helix-turn-helix proteins. Proc Natl Acad Sci U S A 108:13450-5