Tuberculosis is a global epidemic that annually accounts for approximately 2 million deaths worldwide. Because of the capacity of Mycobacterium tuberculosis (Mtb) to establish a latent infection, an estimated 1-2 billion people worldwide are infected with Mtb. Because of this, my long-term goal is to discover the mechansims by which Mtb causes disease in humans. My laboratory is taking an integrated approach, using powerful new molecular genetic, cell biologic, bioinformatic and metabolomic tools to test novel hypotheses and challenge existing paradigms. Our ultimate aim is to use this knowledge to develop new vaccines and treatments for Mtb.
Three key phases in a pathogen’s life cycle dictate its ability to cause disease, namely, i) invasion ii) survival and propagation and iii) escape beyond the host to infect naïve individuals. To date, how Mtb crosses the mucosa and enters the human body is incompletely understood. Likewise, the full repertoire of mechanisms used by Mtb to manipulate and persist within host macrophages is unknown. Additionally, our knowledge of macrophage antimicrobial mechanisms in host defense against Mtb and other pathogens remains incomplete. Enhancing such antimicrobial mechanisms via host-directed therapies is a promising new approach to Mtb treatment. Finally, how Mtb facilitates its own transmission through cough induction has not been studied. Thus, we are addressing these areas of Mtb biology through a series of hypothesis-driven approaches. First, how does Mtb penetrate the nasopharyngeal and respiratory mucosa to cause disease? Second, what are the mechanisms Mtb uses to manipulate host processes to facilitate survival? Third, can host antimicrobial pathways be leveraged to enhance the eradication of intracellular bacteria such as Mtb? Finally, how does Mtb trigger coughing to mediate its spread?
- Medical School
- Cornell University Medical College (2001)
- University of California, San Francisco (2003), Internal Medicine
- University of California at San Francisco (2007), Infectious Diseases
- Innate immune response to intracellular pathogens
- Microbial pathogenesis
- Mucosal immunology
- Mycobacterium tuberculosis
- Role of carbon monoxide (CO) in host-pathogen interactions
- Secretory leukocyte protease inhibitor, an inhibitor of neutrophil activation, is elevated in serum in human sepsis and experimental endotoxemia.
- Grobmyer SR, Barie PS, Nathan CF, Fuortes M, Lin E, Lowry SF, Wright CD, Weyant MJ, Hydo L, Reeves F, Shiloh MU, Ding A Crit. Care Med. 2000 May 28 5 1276-82
- Reactive nitrogen intermediates and the pathogenesis of Salmonella and mycobacteria.
- Shiloh MU, Nathan CF Curr. Opin. Microbiol. 2000 Feb 3 1 35-42
- Lethality of endotoxin in mice genetically deficient in the respiratory burst oxidase, inducible nitric oxide synthase, or both.
- Nicholson SC, Grobmyer SR, Shiloh MU, Brause JE, Potter S, MacMicking JD, Dinauer MC, Nathan CF Shock 1999 Apr 11 4 253-8
- Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase.
- Shiloh MU, MacMicking JD, Nicholson S, Brause JE, Potter S, Marino M, Fang F, Dinauer M, Nathan C Immunity 1999 Jan 10 1 29-38
- Periplasmic superoxide dismutase protects Salmonella from products of phagocyte NADPH-oxidase and nitric oxide synthase.
- De Groote MA, Ochsner UA, Shiloh MU, Nathan C, McCord JM, Dinauer MC, Libby SJ, Vazquez-Torres A, Xu Y, Fang FC Proc. Natl. Acad. Sci. U.S.A. 1997 Dec 94 25 13997-4001
- A novel antioxidant gene from Mycobacterium tuberculosis.
- Ehrt S, Shiloh MU, Ruan J, Choi M, Gunzburg S, Nathan C, Xie Q, Riley LW J. Exp. Med. 1997 Dec 186 11 1885-96
- Evaluation of bacterial survival and phagocyte function with a fluorescence-based microplate assay.
- Shiloh MU, Ruan J, Nathan C Infect. Immun. 1997 Aug 65 8 3193-8
Honors & Awards
- Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases
- The Department of Internal Medicine Chairs Pilot Awards
A Synthetic Lethal Genetic Interaction Map in Mycobacterium tuberculosis (2015-2017)
- UTSW High Impact/High Risk Award
Research award for development of a novel M. tuberculosis vaccine (2012)
- Disease Oriented Clinical Scholar, UTSW
- NIH/NIAID K08 award
- Sandler Family Foundation Discovery Award
Research award for highly innovative research (2006)
- Giannini Family Foundation Research Fellowship, 2005-2008
Honors research fellows in the state of California (2005)
- American Association of Immunologists (2014)
- American Society of Microbiology (2013)
- Infectious Disease Society of America (2010)