Scholars@Duke
David M. Tobin

David M. Tobin

Minnie Geller Distinguished Professor for Research in Genetics
Molecular Genetics and Microbiology
Duke Box 3020, Durham, NC 27710
207 Research Drive, 207A Jones Building, Box 3020, Durham, NC 27710

Featured Works

Macrophage NFATC2 mediates angiogenic signaling during mycobacterial infection.

Journal article Cell Rep · December 13, 2022 Featured Publication During mycobacterial infections, pathogenic mycobacteria manipulate both host immune and stromal cells to establish and maintain a productive infection. In humans, non-human primates, and zebrafish models of infection, pathogenic mycobacteria produce and m ... Full text Open Access Link to item Cite

An ancestral mycobacterial effector promotes dissemination of infection.

Journal article Cell · November 23, 2022 Featured Publication The human pathogen Mycobacterium tuberculosis typically causes lung disease but can also disseminate to other tissues. We identified a M. tuberculosis (Mtb) outbreak presenting with unusually high rates of extrapulmonary dissemination and bone disease. We ... Full text Link to item Cite

Decoding the tuberculous granuloma.

Journal article Immunity · May 10, 2022 Featured Publication In this issue of Immunity,Gideon et al. (2022) couple sophisticated single-cell analyses with detailed in vivo measurements of Mycobacterium tuberculosis granulomas to define the cellular and transcriptional properties of a successful host immune response ... Full text Link to item Cite

A non-canonical type 2 immune response coordinates tuberculous granuloma formation and epithelialization.

Journal article Cell · April 1, 2021 Featured Publication The central pathogen-immune interface in tuberculosis is the granuloma, a complex host immune structure that dictates infection trajectory and physiology. Granuloma macrophages undergo a dramatic transition in which entire epithelial modules are induced an ... Full text Link to item Cite

Potentiation of P2RX7 as a host-directed strategy for control of mycobacterial infection.

Journal article Elife · January 29, 2019 Featured Publication Mycobacterium tuberculosis is the leading worldwide cause of death due to a single infectious agent. Existing anti-tuberculous therapies require long treatments and are complicated by multi-drug-resistant strains. Host-directed therapies have been proposed ... Full text Link to item Cite

An explant technique for high-resolution imaging and manipulation of mycobacterial granulomas.

Journal article Nat Methods · December 2018 Featured Publication A central and critical structure in tuberculosis, the mycobacterial granuloma consists of highly organized immune cells, including macrophages that drive granuloma formation through a characteristic epithelioid transformation. Difficulties in imaging withi ... Full text Link to item Cite

Cyclopropane Modification of Trehalose Dimycolate Drives Granuloma Angiogenesis and Mycobacterial Growth through Vegf Signaling.

Journal article Cell Host Microbe · October 10, 2018 Featured Publication Mycobacterial infection leads to the formation of characteristic immune aggregates called granulomas, a process accompanied by dramatic remodeling of the host vasculature. As granuloma angiogenesis favors the infecting mycobacteria, it may be actively prom ... Full text Link to item Cite

Tuberculous meningitis: a roadmap for advancing basic and translational research.

Journal article Nat Immunol · June 2018 Featured Publication Tuberculous meningitis is a serious, life-threatening disease affecting vulnerable populations, including HIV-infected individuals and young children. The US National Institutes of Health convened a workshop to identify knowledge gaps in the molecular and ... Full text Link to item Cite

Macrophage Epithelial Reprogramming Underlies Mycobacterial Granuloma Formation and Promotes Infection.

Journal article Immunity · October 18, 2016 Featured Publication Mycobacterium tuberculosis infection in humans triggers formation of granulomas, which are tightly organized immune cell aggregates that are the central structure of tuberculosis. Infected and uninfected macrophages interdigitate, assuming an altered, flat ... Full text Link to item Cite

Lysosomal Disorders Drive Susceptibility to Tuberculosis by Compromising Macrophage Migration.

Journal article Cell · March 24, 2016 Featured Publication A zebrafish genetic screen for determinants of susceptibility to Mycobacterium marinum identified a hypersusceptible mutant deficient in lysosomal cysteine cathepsins that manifests hallmarks of human lysosomal storage diseases. Under homeostatic condition ... Full text Open Access Link to item Cite

Direct In Vivo Manipulation and Imaging of Calcium Transients in Neutrophils Identify a Critical Role for Leading-Edge Calcium Flux.

Journal article Cell Rep · December 15, 2015 Featured Publication Calcium signaling has long been associated with key events of immunity, including chemotaxis, phagocytosis, and activation. However, imaging and manipulation of calcium flux in motile immune cells in live animals remain challenging. Using light-sheet micro ... Full text Open Access Link to item Cite

Whole genome sequencing identifies circulating Beijing-lineage Mycobacterium tuberculosis strains in Guatemala and an associated urban outbreak.

Journal article Tuberculosis (Edinb) · December 2015 Featured Publication Limited data are available regarding the molecular epidemiology of Mycobacterium tuberculosis (Mtb) strains circulating in Guatemala. Beijing-lineage Mtb strains have gained prevalence worldwide and are associated with increased virulence and drug resistan ... Full text Open Access Link to item Cite

CLARITY and PACT-based imaging of adult zebrafish and mouse for whole-animal analysis of infections.

Journal article Dis Model Mech · December 2015 Featured Publication Visualization of infection and the associated host response has been challenging in adult vertebrates. Owing to their transparency, zebrafish larvae have been used to directly observe infection in vivo; however, such larvae have not yet developed a functio ... Full text Open Access Link to item Cite

Live Imaging of Host-Parasite Interactions in a Zebrafish Infection Model Reveals Cryptococcal Determinants of Virulence and Central Nervous System Invasion.

Journal article mBio · September 29, 2015 Featured Publication UNLABELLED: The human fungal pathogen Cryptococcus neoformans is capable of infecting a broad range of hosts, from invertebrates like amoebas and nematodes to standard vertebrate models such as mice and rabbits. Here we have taken advantage of a zebrafish ... Full text Open Access Link to item Cite

Interception of host angiogenic signalling limits mycobacterial growth.

Journal article Nature · January 29, 2015 Featured Publication Pathogenic mycobacteria induce the formation of complex cellular aggregates called granulomas that are the hallmark of tuberculosis. Here we examine the development and consequences of vascularization of the tuberculous granuloma in the zebrafish-Mycobacte ... Full text Open Access Link to item Cite

Interception of host angiogenic signalling limits mycobacterial growth

Journal article Nature · January 29, 2015 Featured Publication Pathogenic mycobacteria induce the formation of complex cellular aggregates called granulomas that are the hallmark of tuberculosis. Here we examine the development and consequences of vascularization of the tuberculous granuloma in the zebrafish-Mycobacte ... Full text Cite

Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids.

Journal article Nature · January 9, 2014 Featured Publication The evolutionary survival of Mycobacterium tuberculosis, the cause of human tuberculosis, depends on its ability to invade the host, replicate, and transmit infection. At its initial peripheral infection site in the distal lung airways, M. tuberculosis inf ... Full text Link to item Cite

Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids

Journal article Nature · 2014 Featured Publication The evolutionary survival of Mycobacterium tuberculosis, the cause of human tuberculosis, depends on its ability to invade the host, replicate, and transmit infection. At its initial peripheral infection site in the distal lung airways, M. tuberculosis inf ... Full text Cite

Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections.

Journal article Cell · February 3, 2012 Featured Publication Susceptibility to tuberculosis is historically ascribed to an inadequate immune response that fails to control infecting mycobacteria. In zebrafish, we find that susceptibility to Mycobacterium marinum can result from either inadequate or excessive acute i ... Full text Link to item Cite