- 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 more than 3 million deaths worldwide. Because of the capacity of M. tuberculosis to establish a latent infection, an estimated 2 billion people worldwide are infected with M. tuberculosis. Immunodeficiency caused by malnutrition, old age or HIV infection enhances development of active disease, either from a primary infection or more likely from reactivation of a latent infection. However, the environmental cues responsible for initiating latent infection in the host are not clearly understood. We previously showed that the gas carbon monoxide (CO) produced by host macrophages triggers a dormancy response in mycobacteria mediated by a bacterial two-component system. We also showed that carbon monoxide is well tolerated by mycobacteria, suggesting that mycobacteria can resist CO toxicity, and further have recently discovered a novel gene in M. tuberculosis that affords such resistance. We are currently characterizing the role of this gene in CO resistance, including its precise biochemical mechanism, interacting partners, metabolic effects and role in pathogenesis. Furthermore, we are identifying additional CO resistance genes and characterizing their functions and role in pathogenesis.
In addition to studying the role of carbon monoxide in M. tuberculosis pathogenesis, we are broadly interested in the metabolic and physiologic adaptations of M. tuberculosis during latency. Because successful M. tuberculosis infection occurs as a consequence of complex interactions with the host, we also are studying unique cellular and immunologic responses of the host that facilitate M. tuberculosis survival. Our hope is to identify novel microbial and host factors that can be inhibited or modulated to improve the treatment or prevention of tuberculosis.
- American Association of Immunologists (2014)
- American Society of Microbiology (2013)
- Infectious Disease Society of America (2010)
- 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
- Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases 2018-2023
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
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
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
Mechanisms of mycobacterial transmission: how does Mycobacterium tuberculosis enter and escape from the human host.
Shiloh MU Future microbiology 2016 Dec 11 1503-1506
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
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
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
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 Medical gas research 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 Current opinion in microbiology 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 Molecular microbiology 2005 Jun 56 5 1234-45
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
Reactive nitrogen intermediates and the pathogenesis of Salmonella and mycobacteria.
Shiloh MU, Nathan CF Current opinion in microbiology 2000 Feb 3 1 35-42
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
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
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
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
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
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
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
- A baculovirus-conjugated mimotope vaccine targeting Mycobacterium tuberculosis lipoarabinomannan.
- Innate immune response to intracellular pathogens
- Microbial pathogenesis
- Mucosal immunology
- Mycobacterium tuberculosis
- Role of carbon monoxide (CO) in host-pathogen interactions