- Medical School - Cornell University Medical College (1993-2001)
- Residency - University of California, San Francisco (2001-2003), Internal Medicine
- Fellowship - University of California at San Francisco (2003-2007), Infectious Diseases
Michael Shiloh, M.D., Ph.D.
- Professorship in Infectious Diseases, in honor of James P. Luby, M.D.
- Internal Medicine - Infectious Diseases and Geographic Medicine
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 mechanisms 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 & Training
Professional Associations & Affiliations
- American Association of Immunologists (2014)
- American Society of Microbiology (2013)
- Infectious Disease Society of America (2010)
Honors & Awards
- Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases 2018-2023
- The Department of Internal Medicine Chairs Pilot Awards 2015-2017, A Synthetic Lethal Genetic Interaction Map in Mycobacterium tuberculosis
- UTSW High Impact/High Risk Award 2012, Research award for development of a novel M. tuberculosis vaccine
- Disease Oriented Clinical Scholar, UTSW 2011
- NIH/NIAID K08 award 2008, 2008-2012
- Sandler Family Foundation Discovery Award 2006, Research award for highly innovative research
- Giannini Family Foundation Research Fellowship, 2005-2008 2005, Honors research fellows in the state of California
Books & Publications
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 (Augusta, Ga.) 1999 Apr 11 4 253-8
Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens.
Nathan C, Shiloh MU Proceedings of the National Academy of Sciences of the United States of America 2000 Aug 97 16 8841-8
To catch a killer. What can mycobacterial models teach us about Mycobacterium tuberculosis pathogenesis?
Shiloh MU, DiGiuseppe Champion PA Current opinion in microbiology 2010 Feb 13 1 86-92
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
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
Screening Mycobacterium tuberculosis Secreted Proteins Identifies Mpt64 as a Eukaryotic Membrane-Binding Bacterial Effector.
Stamm CE, Pasko BL, Chaisavaneeyakorn S, Franco LH, Nair VR, Weigele BA, Alto NM, Shiloh MU, mSphere 2019 Jun 4 3
Mycobacterium tuberculosis Sulfolipid-1 Activates Nociceptive Neurons and Induces Cough.
Ruhl CR, Pasko BL, Khan HS, Kindt LM, Stamm CE, Franco LH, Hsia CC, Zhou M, Davis CR, Qin T, Gautron L, Burton MD, Mejia GL, Naik DK, Dussor G, Price TJ, Shiloh MU, Cell 2020 Mar
BECN1F121A mutation increases autophagic flux in aged mice and improves aging phenotypes in an organ-dependent manner.
Sebti S, Zou Z, Shiloh MU, Autophagy 2022 Aug 1-9
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
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 Proceedings of the National Academy of Sciences of the United States of America 1997 Dec 94 25 13997-4001
Mechanisms of mycobacterial transmission: how does Mycobacterium tuberculosis enter and escape from the human host.
Shiloh MU Future microbiology 2016 Dec 11 1503-1506
A baculovirus-conjugated mimotope vaccine targeting Mycobacterium tuberculosis lipoarabinomannan.
Shin HJ, Franco LH, Nair VR, Collins AC, Shiloh MU PloS one 2017 12 10 e0185945
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 Molecular microbiology 2005 Jun 56 5 1234-45
The Ubiquitin Ligase Smurf1 Functions in Selective Autophagy of Mycobacterium tuberculosis and Anti-tuberculous Host Defense.
Franco LH, Nair VR, Scharn CR, Xavier RJ, Torrealba JR, Shiloh MU, Levine B Cell host & microbe 2016 Dec
Evaluation of bacterial survival and phagocyte function with a fluorescence-based microplate assay.
Shiloh MU, Ruan J, Nathan C Infection and immunity 1997 Aug 65 8 3193-8
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
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
Cyclic GMP-AMP Synthase Is an Innate Immune DNA Sensor for Mycobacterium tuberculosis.
Collins AC, Cai H, Li T, Franco LH, Li XD, Nair VR, Scharn CR, Stamm CE, Levine B, Chen ZJ, Shiloh MU Cell host & microbe 2015 Jun
Microfold Cells Actively Translocate Mycobacterium tuberculosis to Initiate Infection.
Nair VR, Franco LH, Zacharia VM, Khan HS, Stamm CE, You W, Marciano DK, Yagita H, Levine B, Shiloh MU Cell reports 2016 Jul
Heme Oxygenase-1 Regulates Inflammation and Mycobacterial Survival in Human Macrophages during Mycobacterium tuberculosis Infection.
Scharn CR, Collins AC, Nair VR, Stamm CE, Marciano DK, Graviss EA, Shiloh MU Journal of immunology (Baltimore, Md. : 1950) 2016 Jun 196 11 4641-9
Identification of scavenger receptor B1 as the airway microfold cell receptor for Mycobacterium tuberculosis.
Khan HS, Nair VR, Ruhl CR, Alvarez-Arguedas S, Galvan Rendiz JL, Franco LH, Huang L, Shaul PW, Kim J, Xie Y, Mitchell RB, Shiloh MU, eLife 2020 Mar 9
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
Sensing of Mycobacterium tuberculosis and consequences to both host and bacillus.
Stamm CE, Collins AC, Shiloh MU Immunological reviews 2015 Mar 264 1 204-19
Infectious and Inflammatory Pathways to Cough.
Naqvi KF, Mazzone SB, Shiloh MU, Annual review of physiology 2022 Sep
A novel antioxidant gene from Mycobacterium tuberculosis.
Ehrt S, Shiloh MU, Ruan J, Choi M, Gunzburg S, Nathan C, Xie Q, Riley LW The Journal of experimental medicine 1997 Dec 186 11 1885-96
Effect of carbon monoxide on Mycobacterium tuberculosis pathogenesis.
Zacharia VM, Shiloh MU Medical gas research 2012 2 1 30
Bag it, tag it: ubiquitin ligases and host resistance to Mycobacterium tuberculosis.
Campos PC, Cunha DT, Souza-Costa LP, Shiloh MU, Franco LH, Trends in microbiology 2022 Apr
EBV-driven HIV-associated diffuse large B-cell lymphoma causing profound lactic acidosis.
Prokesch BC, Shiloh MU Blood 2014 Aug 124 6 842
Reactive nitrogen intermediates and the pathogenesis of Salmonella and mycobacteria.
Shiloh MU, Nathan CF Current opinion in microbiology 2000 Feb 3 1 35-42
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 Critical care medicine 2000 May 28 5 1276-82
- Lethality of endotoxin in mice genetically deficient in the respiratory burst oxidase, inducible nitric oxide synthase, or both.
- Innate immune response to intracellular pathogens
- Microbial pathogenesis
- Mucosal immunology
- Mycobacterium tuberculosis
- Role of carbon monoxide (CO) in host-pathogen interactions