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
- EBV-driven HIV-associated diffuse large B-cell lymphoma causing profound lactic acidosis.
- Prokesch BC, Shiloh MU Blood 2014 Aug 124 6 842
- The ubiquitin ligase parkin mediates resistance to intracellular pathogens.
- Manzanillo PS, Ayres JS, Watson RO, Collins AC, Souza G, Rae CS, Schneider DS, Nakamura K, Shiloh MU, Cox JS Nature 2013 Sep 501 7468 512-6
- cor, a Novel Carbon Monoxide Resistance Gene, Is Essential for Mycobacterium tuberculosis Pathogenesis.
- Zacharia VM, Manzanillo PS, Nair VR, Marciano DK, Kinch LN, Grishin NV, Cox JS, Shiloh MU MBio 2013 4 6
- Mycobacterium tuberculosis activates the DNA-dependent cytosolic surveillance pathway within macrophages.
- Manzanillo PS, Shiloh MU, Portnoy DA, Cox JS Cell Host Microbe 2012 May 11 5 469-80
- Effect of carbon monoxide on Mycobacterium tuberculosis pathogenesis.
- Zacharia VM, Shiloh MU Med Gas Res 2012 2 1 30
- Mycobacterium tuberculosis MycP1 protease plays a dual role in regulation of ESX-1 secretion and virulence.
- Ohol YM, Goetz DH, Chan K, Shiloh MU, Craik CS, Cox JS Cell Host Microbe 2010 Mar 7 3 210-20
- To catch a killer. What can mycobacterial models teach us about Mycobacterium tuberculosis pathogenesis?
- Shiloh MU, DiGiuseppe Champion PA Curr. Opin. Microbiol. 2010 Feb 13 1 86-92
- Mycobacterium tuberculosis senses host-derived carbon monoxide during macrophage infection.
- Shiloh MU, Manzanillo P, Cox JS Cell Host Microbe 2008 May 3 5 323-30
- A glutamate-alanine-leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages: role of cyclic diGMP.
- Hisert KB, MacCoss M, Shiloh MU, Darwin KH, Singh S, Jones RA, Ehrt S, Zhang Z, Gaffney BL, Gandotra S, Holden DW, Murray D, Nathan C Mol. Microbiol. 2005 Jun 56 5 1234-45
- Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens.
- Nathan C, Shiloh MU Proc. Natl. Acad. Sci. U.S.A. 2000 Aug 97 16 8841-8
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)