Research in the Department of Microbiology and Immunology
With 11 faculty members, a staff of 28 research associates and postdocs and 12 Ph.D. students, Ira Schwartz, Ph.D., professor and chairman, oversees a department with research funded by grants from the National Institutes of Health, the American Heart Association and other sources, totaling more than $5 million per year.
Research in the department is concentrated in two areas—infectious diseases and cancer biology. In general, the researchers studying infectious diseases are looking at what properties of microbes cause invasive or more serious disease, and the evolutionary relationships between different strains of pathogens. The cancer biology focus includes studies on prostate and breast and glioma. In collaboration with clinician researchers in departments like pediatrics, medicine and otolaryngology, investigators are involved in translational research—bringing new discoveries and research insights to the patients’ bedside.
“Microbiology and immunology are key to understanding basic life processes. They are also instrumental in the quest to improve the quality of life by addressing important public health problems,” says Dr. Schwartz. “In our department, we’re committed to working as a team toward discoveries that could lead to novel approaches to treat an assortment of diseases. And we’re also training the next generation of physicians and scientists.”
Ranjit Banerjee, Ph.D., assistant professor, is examining the effect of various host cell factors in controlling the infectivity and pathogenicity of human immunodeficiency virus (HIV-1), as well as human hepatitis B and hepatitis C viruses. Using various cloned cellular models, he is studying the function of the cellular proteins and other macromolecules affecting these viral regulatory motifs. By identifying novel genes and cell signaling pathways, he can better characterize the differences between the disease progressors and non-progressors, interactions between these viruses in the host, and the effectiveness of certain drug therapies.
Debra Bessen, Ph.D., professor, leads a research team focused on understanding the bacterial pathogen, group A streptococcus, the causative agent of strep throat. One of the fundamental questions is why some streptococcal strains cause pharyngitis, whereas other strains cause skin infections (impetigo). The differential expression of genes encoding virulence factors appears to hold some answers. The lab takes a multifaceted approach that integrates molecular studies with animal models, population biology and genomics. In other studies, the role of streptococcal infection as a trigger for pediatric autoimmune neuropsychiatric disorders, such as Tourette syndrome and obsessive-compulsive disorder, is being investigated. Present collaborations include investigators at the Institute for Genome Sciences (Baltimore) and Yale University.
Doris L. Bucher, Ph.D., associate professor, oversees the laboratory that develops high-yield reassortant strains for the production of the world’s annual supply of influenza vaccine—some 400 million doses worldwide. Each year’s vaccine is different, containing the three strains that health officials believe are most likely to emerge during the subsequent flu season. Vaccine production is a lengthy process that takes about six months. In developing vaccine strains, the genes of the current virus are reassorted with the high-yield PR/8 virus to allow incorporation of its high-growth genes. This year, the strain created by Dr. Bucher’s lab—NYMC X-175C—comprises the H3N2 component that will go into the influenza vaccine, with 145 million doses destined for the U.S.
The laboratory of Felipe C. Cabello, M.D., professor, is involved in the analysis of the mechanisms used by Borrelia burgdorferi, the organism that causes Lyme disease, to regulate expression of its virulence genes. This includes study of global mechanisms such as the stringent response mediated by the alarmone (p)ppGpp that affects many genes, as well as mechanisms whose effect is localized to a single gene. The laboratory is also involved in the development of genetic tools to manipulate B. burgdorferi including antisense RNA and new antibiotic resistance markers. More recently, Dr. Cabello received a grant to study the effects of excessive use of antibiotics in salmon aquaculture. This research will help to determine whether there is traffic of antibiotic-resistant genes between marine bacteria, including fish and human pathogens.
Jan Geliebter, PhD, professor, investigates the molecular mechanisms in papillary thyroid cancer, with the hope that these molecular studies will lead to better diagnostic and prognostic tools as well as potential therapeutic targets for the treatment of the disease. Dr. Geliebter also studies the interplay of aging, diet and oxidative stress in the etiology of prostate cancer, as well as immuotherapeutic approaches for the treatment of cancer.
Carl V. Hamby, Ph.D., associate professor, is pursuing translational research centered around the development and testing of recombinant cytotoxic proteins for therapy of melanoma, glioma, and medulloblastoma tumors. Using potent bacterial toxins linked to human growth factors to target tumor cells, or the tumor vasculature-expressing growth factor receptors that sustain tumor growth, the team hopes to develop therapeutics that can eradicate microscopic residual tumors that may be left behind following surgical excision or that have disseminated from the original tumor. In addition, Dr. Hamby’s laboratory investigates molecular mechanisms of tumor metastasis with particular emphasis on the role of nm23 genes in regulating this process.
Dana G. Mordue Ph.D., assistant professor, studies the model intracellular protozoa Toxoplasma gondii, which causes toxoplasmosis. In particular, the group is investigating novel molecular mechanisms used by this intracellular pathogen to subvert the host innate immune response and to adapt to changes in the microenvironment during infection. Dr. Mordue’s team utilizes genetic and global microarray-based approaches to identify parasite genes that are differentially regulated by the host’s innate immune response during infection.
Ira Schwartz, Ph.D., professor and chairman, studies emerging tick-borne infectious diseases, primarily Lyme disease. His group was among the first to develop and apply PCR and quantitative PCR to patient and tick samples, leading to practical measurements of tick-borne disease risk and have developed molecular typing approaches for differentiating genotypes of Borrelia burgdorferi among Lyme disease patient isolates, resulting in identification of a B. burgdorferi genotype that is more frequently associated with disseminated infection in early Lyme disease patients. Dr. Schwartz's laboratory is currently using functional genomic approaches to identify genes that are responsible for B. burgdorferi dissemination and pathogenesis and those that mediate the human response to infection.
Raj Tiwari, Ph.D., professor, is studying prevention and treatment of cancer specifically the hormonally modulated cancers, breast, prostate and thyroid. We are developing a peptide based multi-valent approach towards prostate and breast cancer and have identified several anti-tumor peptides capable of inducting a robust immune response. These immunological approaches together with chemotherapy and novel stem cell therapy are being used to develop cutting edge combination therapeutic modalities. The Tiwari laboratory also has a program in thyroid cancer, which involves developing prognostic markers and using dietary and stem cell approaches to interact with hormonal responses in treating thyroid proliferative diseases.