Michael Starnbach, PhD
Department of Microbiology and Molecular Genetics, Harvard Medical School
Bacterial infection and acquired immunity
T-cell response to bacterial infection, including sexually transmitted chlamydia disease
To extend the Chlamydia findings in mice to primate models and eventually to human clinical trials
Identify antigenic determinants of Chlamydia and other bacterial pathogens suitable as druggable antibiotic targets; Pinpoint host factors that participate in the interferon-dependent signaling responsible for conferring immunity to bacterial infections, as a prerequisite for developing novel anti-bacterial treatments
Current Research Interests
- Employ retrogenic mouse models engineered to express TCR clones for specific bacterial antigenic epitopes in naïve T-cells in order to study bacterial infection and mechanisms of adaptive immunity, with a particular focus on Chlamydia, Salmonella, and Legionella.
- Investigate the T-cell response to bacterial infection in the genital tract as well as other mucosal surfaces.
- Dissect the components of the host interferon-dependent signaling pathways responsible for generating immunity to bacterial infections, and determine if multiple interferon-dependent pathways exist to quell different bacterial pathogens.
- Investigate mammalian host factors that modulate the immune response to pathogenic bacterial infection.
- Dr. Starnbach is interested in understanding genetic and biochemical mechanisms underlying the T-cell response to bacterial infection as well as the complex interplay of pathogen and host molecules that either orchestrate immune evasion and promulgation of infection or consort to suppress bacterial survival and replication.
- He has exploited advanced retrogenic mouse technology to study in vivo naïve T-cells harboring cloned TCRs as a surrogate for investigating the immune response to bacterial organisms.
- Dr. Starnbach is employing retrogenic mouse technology, global RNAi genetic screens for host factors involved in the immune response triggered by bacterial infection, non-toxic recombinant toxins for in vivo expression of bacterial and viral epitopes.
Dr. Starnbach’s laboratory has published high-profile articles on the T-cell response to bacterial infections, including bacterial-induced immunosuppression and sexually transmitted disease (STD) caused by Chlamydia, the most prevalent bacterial STD in the US. His recent studies have illuminated a key aspect of the immune response to chlamydia infection. He employed a “retrogenic” methodology that allows the study of naïve T-cell reactions, in which bone marrow cells transduced with a retrovirus containing a cloned TCR specific for a Chlamydia antigenic epitope were used to repopulate irradiated mice (i.e., a retrogenic mouse strain). He found that antigen-specific CD8+ T cells proliferated and secreted interferon when the retrogenic mice were exposed to genital tract Chlamydia infection. In fact, these clonal T cells displayed homing to the genital mucosa, demonstrating an important facet of the adaptive immune response to Chlamydia infection. Corroborative studies employed TCR transgenic mice specific for a different Chlamydia antigen. Dr. Starnbach has also found that Salmonella have the intriguing capability to directly block T-cell activation through a contact-dependent process.