Name: Michael T. Berton, Ph.D.

Title:  Associate Professor

Department of Microbiology and Immunology

Location:         4.037V

Phone:             (210) 567-3931

Fax:                 (210) 567-6428

E-mail:             Berton@uthscsa.edu

Web link:         http://www.uthscsa.edu/micro/faculty/mtb.htm

 

Research Interests:

My laboratory is focused on the regulation of host immune responses by host cell signaling pathways. This question is currently explored in two distinct model systems. The first system focuses on the role of Toll-like receptor (TLR) signaling primarily in macrophages and dendritic cells during the immune response to the intracellular bacterial pathogen, Francisella tularensis. The second model system focuses on cytokine signaling mechanisms that regulate responses during infection, inflammation and allergy.

 

The innate immune response to many pathogens is initiated when the host is alerted to infection as a result of recognition of pathogen-derived molecules by the Toll-like receptors (TLRs), members of a broader family of pattern recognition molecules that recognize and bind to conserved molecular motifs expressed by many pathogens. The TLRs are evolutionarily conserved germline-encoded receptors that signal many cell types via a set of conserved signaling molecules that lead to MAP kinase and NF-κB activation. Binding of TLRs to their respective ligands induces the expression of chemokines, pro-inflammatory cytokines and upregulation of MHC and co-stimulatory molecules on macrophage and dendritic cells. Francisella tularensis is a gram-negative, facultative intracellular bacterial pathogen that causes the disease tularemia. Because of the high infectivity, virulence and ability to be disseminated by aerosol, Francisella tularensis type A and B strains are classified as Category A bioweapon agents by the CDC. Numerous studies have indicated a critical role for the innate immune response in protection against infection with F. tularensis, but very little is known about activation of the innate response to this organism. Our interest is to elucidate the role of TLR signaling pathways in the innate and adaptive immune responses to infection with F. tularensis in a mouse model of pulmonary tularemia. Our studies are focused on identifying TLR ligands produced by F. tularensis and the mechanisms by which TLR signaling mediates activation and/or evasion of host effector mechanisms.

 

The second major interest in my laboratory is in understanding how the cytokine interleukin 4 (IL-4) and the transcription factor Stat6 regulate cell-type specific gene expression. This is important because IL-4 regulates critical immune processes such as the development of T helper cells and immunoglobulin isotype switching in B cells. Specifically, IL-4 promotes the development of T helper 2 cells which then make more IL-4 that can induce B cells to switch from the expression of IgM and IgD to the expression of IgE, which is critical for the development of allergy. Our current efforts are focused on the role of post-translational modifications of Stat6, such as serine phosphorylation, and interactions with other regulatory proteins in modulating IL-4/Stat6-dependent gene expression in B and T cells.

 

Unique Technical and Clinical Research Capabilities/Instrumentation:

molecular cloning, RT-PCR, promoter analysis, phosphoprotein analysis, baculovirus expression

 

Key Words:

Regulation of immunity in infection, allergy and cancer; cytokine and Toll-like receptor signal transduction, regulation of gene expression