Intestinal chloride secretion is stimulated during diarrhea. Cholera toxin is secreted by bacterium Vibrio cholera and is responsible for the watery diarrhea after cholera infection. Mechanistically, cholera toxin increases intracellular cyclic AMP, which subsequently activates protein kinase A and the cystic fibrosis transmembrane regulator chloride channel (CFTR). However, we recently identified an intestinal cAMP-Ca cross-talk signaling pathway that is initiated by elevation of intracellular cAMP and subsequently elevates intracellular Ca concentrations through the exchange protein activated by cAMP (Epac). This observation suggests that both CFTR and calcium-activated chloride channels are targets of elevated intracellular cAMP signaling molecule. Therefore, we are studying the role of calcium-activated Cl channels in intestinal chloride secretion under physiological conditions and during diarrhea. We are also determining whether the recently identified transmembrane protein 16 family of proteins, which are calcium-activated chloride channels, is also involved in intestinal chloride secretion in addition to the well characterized CFTR channel. Increased understanding of regulation of intestinal Cl secretion provides the necessary background information for the development of therapeutic drugs for the treatment of diarrhea, constipation and cystic fibrosis. The discovery that calcium-activated chloride channels are involved in intestinal chloride secretion provides additional targets for anti-diarrhea drug development.

Research in the Meredith McCormack Lab deals primarily with pulmonary diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and the role of environmental exposures in lung diseases. We have researched the factors that contribute to inner-city asthma, with a focus on how particulate matter air pollution impacts pulmonary function. We are also part of the LIBERATE clinical study, which is focused on patients who experience difficulty breathing and have been diagnosed with severe emphysema. We also have a longstanding interest in the effects of race/ethnicity, poverty and urbanization on nutrition and food allergies.

The Michael Klag Lab focuses on the epidemiology and prevention of kidney disease, cardiovascular disease and hypertension. Our research determined that the U.S. was experiencing an epidemic of end-stage kidney disease, pinpointed the incidence of kidney disease and published scholarship on risk factors for kidney disease such as race, diabetes and socioeconomic status. Our Precursors Study has shown that serum cholesterol measured at age 22 years is a predictor for midlife cardiovascular disease, a finding that has influenced policy about cholesterol screening in young adults. We also research health behaviors that lead to hypertension and study how differences in these behaviors affect urban and non-urban populations.

The O'Connor Lab studies the molecular basis of infectious disease using Legionella pneumophila pathogenesis as a model system. We are looking at the network of molecular interactions acting at the host-pathogen interface. Specifically, we use L. pneumophila pathogenesis to examine the numerous mechanisms by which an intracellular bacterial pathogen can establish infection, how it exploits host cell machinery to accomplish this, and how individual proteins and their component pathways coordinately contribute to disease. We are also studying the role of environmental hosts in the evolution of human pathogens. Using genetics and functional genomics, we compare and contrast the repertoires of virulence proteins required for growth in a broad assortment of hosts, how the network of molecular interactions differs between hosts, and the mechanisms by which L. pneumophila copes with this variation.

The Rao Laboratory studies the roles of intracellular cation transport in human health and disease using yeast as a model organism. Focus areas include intracellular Na+(K+)/H+ exchange and Golgi CA2+(MN+) ATPases.