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David Tobin

Assistant Professor
Molecular Genetics and Microbiology
(919) 684-9152
Research Interest: 
Microbiology and virology
Research Summary: 
Tuberculosis: Mycobacterial pathogenesis and host susceptibility.
Research Description: 

Tuberculosis kills 1.5 million people annually. Our laboratory aims to understand the intricate interplay between mycobacteria and their hosts using a combination of model organism genetics, human genetics, pharmacology and high-resolution microscopy. By identifying key pathways utilized by the infecting bacteria and the host innate immune system, we hope to discover new therapeutic targets and interventions to combat this enduringly destructive disease.

Using a Mycobacterium/zebrafish model, we have identified new host susceptibility loci for tuberculosis. Zebrafish are natural hosts to Mycobacterium marinum, the closest relative of the Mycobacterium tuberculosis complex. Because zebrafish embryos and larvae are optically transparent, we are able to visualize the complex details of mycobacterial pathogenesis in whole, live animals. The facile genetics of the zebrafish allow us to map and positionally clone affected host susceptibility genes. In addition, zebrafish larvae are remarkably permeable to small molecules, providing a platform for whole-animal pharmacological manipulation of specific host immune responses.

We have identified novel pathways that modulate susceptibility to tuberculosis. We have shown that genes identified in the zebrafish model are also important in human tuberculosis. We find robust associations of human variants in a specific eicosanoid pathway with susceptibility to both tuberculosis and leprosy.

We have active collaborations in both Vietnam and Guatemala. In Guatemala, we are working with the Clínica Familiar Luis Angel García and the Asociación de Salud Integral to support projects involving HIV-infected patients and to understand the dynamics of TB transmission in Central America.

Host-Directed Therapies for Tuberculosis.
Tobin DM.
Cold Spring Harb Perspect Med. 2015. 5: .

Interception of host angiogenic signalling limits mycobacterial growth.
Oehlers SH, Cronan MR, Scott NR, Thomas MI, Okuda KS, Walton EM, Beerman RW, Crosier PS, Tobin DM.
Nature. 2015. 517:612-5.

Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids.
Cambier CJ, Takaki KK, Larson RP, Hernandez RE, Tobin DM, Urdahl KB, Cosma CL, Ramakrishnan L.
Nature. 2014. 505:218-22.

Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections.
Tobin DM, Roca FJ, Oh SF, McFarland R, Vickery TW, Ray JP, Ko DC, Zou Y, Bang ND, Chau TT, Vary JC, Hawn TR, Dunstan SJ, Farrar JJ, Thwaites GE, King MC, Serhan CN, Ramakrishnan L.
Cell. 2012. 148:434-46.

The lta4h locus modulates susceptibility to mycobacterial infection in zebrafish and humans.
Tobin DM, Vary JC, Ray JP, Walsh GS, Dunstan SJ, Bang ND, Hagge DA, Khadge S, King MC, Hawn TR, Moens CB, Ramakrishnan L.
Cell. 2010. 140:717-30.