The last century is notable for the remarkable successes made in the area of antibiotic and vaccine development against infectious agents. However, as we begin this century, the singular most common cause of morbidity and mortality in man and animals is once again infectious diseases. With the anticipated growth in the aged and immunocompromised populations in our midst and the rapid emergence of multiresistant bacteria, there is an acute need for the development of alternate approaches to curb microbial infections and their harmful sequellae.
This laboratory is interested in developing innovative approaches for curbing microbial infections through the study of the molecular interactions occurring between pathogenic bacteria and prominent immune and epithelial cells. We believe that there is a significant amount of crosstalk occurring between bacteria and host cells during infection and that the outcome of this interaction dictates both how quickly the infection is cleared and the severity of the pathology associated with the infection. We also believe that through deciphering this crosstalk we should be able to selectively promote certain beneficial interactions while abrogating the harmful ones. In so doing, we hope to minimize the severity of the infection and achieve more rapid clearance of the pathogen.
There are two major research areas being pursued in this laboratory. The first is centered around elucidating how mast cells, frequently overlooked players in initiating and maintaining host immune responses, mobilize key components of the immune system during bacterial infections. Ultimately, the goal of these studies is to harness some of these activities attributed to mast cells for therapeutic or vaccine development purposes. The second area of research within our laboratory focuses on understanding how uropathogenic Escherichia coli, the overwhelmingly predominate causative agent of urinary tract infections, successfully gains entry into epithelial cells of the bladder to cause infection. This subject is especially intriguing because of the role the bladder plays as a reservoir for urine. Predictably the "water-tight" epithelial barrier of the bladder is especially difficult for bacteria to breech. Yet, E.coli, which compared to other pathogens have no specialized organelles for cell entry, appears to achieve this feat. We believe that by investigating the molecular events associated with the entry of E.coli into bladder epithelial cells and the resulting break down of the bladder barrier, we will be able to develop novel strategies to prevent these infections.
Other studies currently undertaken by one or more members of the laboratory include (i) examination of how particulate allergens interact with pulmonary mast cells to trigger air way hyperesponses and pulmonary inflammation. (ii) investigation of how, during infection, highly virulent pathogens such as Yersinia pestis, Salmonella typhimurium, etc., actively remodel the draining lymph nodes, the epicenter of the adaptive immune response (iii) investigation of how Pseudomonas aeruginosa co-opts cellular entities generally known as lipid rafts to colonize the airways.
Our studies are located at the intersection of cell biology, molecular biology, immunology and bacterial pathogenesis. Cumulatively, our studies should facilitate the design of innovative strategies to combat pathogens that selectively potentiate the hosts immune response without evoking some of its harmful side effects.