Professor of Microbiology and Immunology, Adjunct Professor of Oral Biology
Allergy and Immunology; Apoptosis and cell death; Bacterial Pathogenesis; Gene Expression; Genomics and proteomics; Immunology; Infectious Disease; Medical Microbiology; Microbial Pathogenesis; Microbiology; Molecular and Cellular Biology; Molecular Basis of Disease; Molecular genetics; Protein Function and Structure; Signal Transduction
Research efforts in my laboratory are focused in the fields of immunology and bacterial pathogenesis, two diverse fields of biomedical research for which I have two separate research groups. Projects in both fields are performed by undergraduates, doctoral and master’s degree students, postdoctoral fellows and senior research associates.
One major focus of my laboratory is studying the regulation of mucosal immune responses. We investigate the cellular and molecular events by which Type II heat-labile enterotoxins (HLTs), produced by certain strains of Escherichia coli, modulate immune responses. We have demonstrated that LT-Ila, LT-IIb and LT-IIc, when co-administered with an antigen, have the capacity to enhance antibody and cellular immune responses to that antigen. Using a variety of immunological and cellular technologies, including flow cytometry, fluorescence resonance energy transfer (FRET) detection, cytokine multiplex analysis, mutagenesis, quantitative Reverse Transcription PCR (qRT-PCR), RNA-sequencing (RNA-Seq) and a variety of transgenic mice, we are investigating the mechanisms by which these immunomodulators productively interact with various immunocompetent cells (T cells, B cells, dendritic cells, macrophages) to induce or suppress cytokine production, costimulatory ligand expression and cellular proliferation. A practical outgrowth of these experiments is the potential to engineer novel recombinant vaccines by genetically fusing antigens from different pathogens to the enterotoxins. Recent experiments have shown that these HLT are lethal for triple-negative breast cancer cells, which has opened a new area of oncological research for the lab.
A second focus of my laboratory is to investigate the cytotoxic activities of the type II heat-labile enterotoxins for triple-negative breast cancer cells. Treatment of both cancer cell lines and primary cancer cells obtained from human tumors with LT-IIc elicits unusual vacuolation in the cells, enhanced autophagy, stalled autophagic flux, apoptosis, and necroptosis. Our laboratory is engaged in identifing the cellular mechanisms underlying those activities of LT-IIc with the goal of investigating those cytotoxic pathways to develop new pharmacological agents to treat triple-negative breast cancer, a type of cancer with poor prognosis and few treatment options.
In the last five years, we have evaluated the capacity of LT-IIc to specifically kill triple-negative breast cancer cells without having an effect on non-cancerous breast epithelial cells. This cytotoxic activity is induced in both TNBC cell lines and in breast cancer cells isolated from primary human tumors. Recently, we have demonstrated that binding of the toxin to its receptors on the cancer cell surface is sufficient to induce cytotoxicity. Currently, we are focused on identifying those receptors.