Biography

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?

Education

Medical School
Cornell University Medical College (2001)
Residency
University of California, San Francisco (2003), Internal Medicine
Fellowship
University of California at San Francisco (2007), Infectious Diseases

Research Interest

  • Innate immune response to intracellular pathogens
  • Microbial pathogenesis
  • Mucosal immunology
  • Mycobacterium tuberculosis
  • Role of carbon monoxide (CO) in host-pathogen interactions

Publications

Featured Publications LegendFeatured Publications

Sensing of Mycobacterium tuberculosis and consequences to both host and bacillus.
Stamm CE, Collins AC, Shiloh MU Immunol. Rev. 2015 Mar 264 1 204-19
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

Honors & Awards

  • Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases
    (2018-2023)
  • The Department of Internal Medicine Chair’s 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
    (2011)
  • NIH/NIAID K08 award
    2008-2012 (2008)
  • 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)

Professional Associations/Affiliations

  • American Association of Immunologists (2014)
  • American Society of Microbiology (2013)
  • Infectious Disease Society of America (2010)