Stanley M. Spinola, M.D.
Professor and Chair, Department of Microbiology and Immunology
Professor of Medicine, Microbiology & Immunology, Pathology, and Laboratory Medicine
Summary of the focus of the research of Dr. Spinola
The Spinola laboratory focuses on the pathogenesis of and host response to the bacterium Haemophilus ducreyi in an experimental model of human infection and on novel strategies for antimicrobial drug development.
Description and summary of research focus of the research of Dr. Spinola.
The Spinola laboratory focuses on the pathogenesis of and host response to the bacterium Haemophilus ducreyi, which causes nonsexually transmitted cutaneous ulcers in children in the tropics and the genital ulcer disease chancroid, which facilitates the transmission of HIV-1. We developed a model in which human volunteers are infected on the skin of the arm with the bacterium that is relevant to both syndromes. Features of the model include a low dose required for infection (1 to 100 CFU) and a clinical course and a cutaneous immune response that mimics naturally occurring disease. In both experimental and natural infection, H. ducreyi resides in an abscess, and the primary mechanism by which the organism causes disease is evasion of phagocytosis. One major project in the laboratory is to determine the molecular interaction network between H. ducreyi and the host on a transcriptional level using RNA-sequencing; our preliminary data indicate that H. ducreyi is primarily seeking nutrients and adapting to anaerobiasis in vivo. As a result of our H. ducreyi pathogenesis studies, we found that activation of a two-component system cripples the virulence of H. ducreyi and 3 other antibiotic resistant gram negative pathogens. We have identified small molecules that activate this system in E. coli as potential antimicrobials. There are currently 1 technician, 1 postdoctoral fellow and 1 Research Associate in the laboratory. New trainees will be exposed to molecular biology, immunology, cell biology, therapeutics and the methods and ethics of human research.
- *Gangaiah D, *Labandeira-Rey M, Zhang X, Fortney KR, Ellinger S, Zwickl BW, Baker B, Liu Y, Janowicz DM, Katz BP, Brautigam CA, Munson, RS, Jr., Hansen EJ, Spinola SM. Haemophilus ducreyi Hfq Contributes to Virulence Gene Regulation as Cells Enter Stationary Phase. MBio 2014; 5(1):e01028-13. doi: 10.1128/mBio.01081-13. PMCID: PMC3950518
- Zhang X, Gangaiah D, Munson, RS, Jr., Spinola SM, Liu Y. Correcting imbalanced reads coverage in bacterial transcriptome sequencing with extreme deep coverage. International Journal of Computational Biology and Drug Design. 2014; 7: 195-213.
- Holley C, Gangaiah D, Li W, Fortney KR, Janowicz DM, Ellinger S, Zwickl B, Katz BP, Spinola SM. A (p)ppGpp null mutant of Haemophilus ducreyi is partially attenuated in humans due to multiple conflicting phenotypes Infect. Immun. 2014; 82: 3492-3501. PMCID: PMC4136218
- Gangaiah D, Zhang X, Fortney KR, Baker B, Liu Y, Munson, RS, Jr., Spinola SM. Haemophilus ducreyi RpoE and CpxRA appear to play distinct yet complementary roles in regulation of envelope-related functions. J. Bacteriol. 2014; 196: 4012-4025. PMCID: PMC4248869
- Trombley MP, Post DM, Rinker SD, Reinders LM, Fortney KR, Zwickl BW, Janowicz DM, Baye FM, Katz BP, Spinola SM, Bauer ME. Phosphoethanolamine transferase LptA in Haemophilus ducreyi modifies Lipid A and contributes to human defensin resistance in vitro. PLoS One 2015; Apr 22;10(4):e0124373. PMCID: PMC4406763
- van Rensburg JJ, Fortney KR, Chen L, Kreiger A, Lima BP, Wolfe AJ, Katz BP, Zhang Z-Y, Spinola SM. Development and validation of a high-throughput cell-based screen to identify activators of a bacterial two-component signal transduction system. Antimicrob Agents Chemother. 2015; 59: 3789-3799. PMCID: PMC25870061
- Gangaiah D, Webb KM, Humphreys TL, Fortney KR, Toh E, Tai A, Katz SS, Pillay A, Chen C-Y, Roberts SA, Munson, RS, Jr., Spinola SM. Haemophilus ducreyi cutaneous ulcer strains are nearly identical to Class I genital ulcer strains. PLoS Neglected Tropical Diseases 2015; July 6; 9(7): e0003918. PMCID: PMC4492979
- Holley C, Zhang X, Fortney KR, Ellinger S, Johnson P, Baker B, Liu Y, Janowicz DM, Katz BP, Munson, RS, Jr., Spinola SM. DksA and (p)ppGpp have unique and overlapping contributions to Haemophilus ducreyi pathogenesis in humans. Infect. Immun. 2015; 83: 3281-3292. PMCID: PMC4496623.
- *van Rensburg JJ, Lin H, Gao X, Toh E, Fortney KR, Ellinger S, Zwickl B, Janowicz DM, Katz BP, Nelson DE, Dong Q, Spinola SM. The Human Skin Microbiome Associates with the Outcome of and Is Influenced by Bacterial Infection. mBio. 2015;6(5). doi: 10.1128/mBio.01315-15. PubMed PMID: 26374122
* Featured in The Scientist, 9/6/15
- Undergraduate: Brown University, B.A. in Biology, Magna Cum Laude, 1974
- Graduate: Georgetown University, M.D., Cum Laude, 1978
- Postdoctoral: Combined internship and residency in Internal Medicine and Pediatrics, University of North Carolina, Chapel Hill, 1978 to 1982
- Adult and Pediatric Infectious Diseases, University of North Carolina, Chapel Hill, 1984 to 1987; trained with Dr. Janne Cannon, Department of Microbiology and Immunology