Secretory diarrhea is a leading cause of childhood morbidity and mortality in developing countries. While diarrhea can be treated with oral rehydration solution (ORS), inclusion of zinc with oral ORS has been shown to reduce the duration of diarrhea. However, how zinc improves diarrhea is not known. It has been shown that zinc acts as an intestinal epithelial cell basolateral potassium channel blocker of cyclic AMP-mediated chloride secretion. We discovered that zinc also stimulates intestinal sodium and water absorption via the epithelial Na/H exchanger, NHE3. Zinc reverses the effect of cyclic AMP inhibition of NHE3 activity. The effect of zinc on NHE3 cannot be duplicated with other divalent metal ions. It has been well established that Na/H exchanger regulatory proteins are involved in NHE3 regulation. Whether these regulatory proteins are involved in zinc stimulation of NHE3 is a focus of our study. Our goal is to reveal mechanisms to explain how zinc improves diarrhea and to understand the role of zinc in salt and water homeostasis in the gut. Our study will provide a scientific basis to justify the inclusion of zinc in ORS for the treatment of secretory diarrhea.

The In-vivo Cellular and Molecular Imaging Center conducts multidisciplinary research on cellular and molecular imaging related to cancer. We provide resources, such as consultation on biostatistics and bioinformatics and optical imaging and probe development, to understand and effectively treat cancer. Our molecular oncology experts consult on preclinical studies, use of human tissues, interpretation of data and molecular characterization of cells and tumor tissue.

Research in the Ivor Berkowitz Lab targets pediatric critical care medicine. We are particularly interested in the pathophysiology behind the cerebrovascular dysfunction that occurs in bacterial meningitis as well as the anesthetic and perioperative complications of patients with dwarfing syndromes.

Research in the J. Hunter Young Lab focuses on the genetic epidemiology and physiology of cardiovascular disease and its risk factors, especially hypertension, diabetes and obesity. Current activities include an observational study of hypertension among African Americans; a genetic epidemiology study of worldwide cardiovascular disease susceptibility patterns; and several population-based observational studies of cardiovascular and renal disease. A recent focus group study found that changes in housing and city policies might lead to improved environmental health conditions for public housing residents.

Our research is focused on understanding the basic mechanisms of programmed cell death in disease pathogenesis. Billions of cells die per day in the human body. Like cell division and differentiation, cell death is also critical for normal development and maintenance of healthy tissues. Apoptosis and other forms of cell death are required for trimming excess, expired and damaged cells. Therefore, many genetically programmed cell suicide pathways have evolved to promote long-term survival of species from yeast to humans. Defective cell death programs cause disease states. Insufficient cell death underlies human cancer and autoimmune disease, while excessive cell death underlies human neurological disorders and aging. Of particular interest to our group are the mechanisms by which Bcl-2 family proteins and other factors regulate programmed cell death, particularly in the nervous system, in cancer and in virus infections. Interestingly, cell death regulators also regulate many other cellular processes prior to a death stimulus, including neuronal activity, mitochondrial dynamics and energetics. We study these unknown mechanisms. We have reported that many insults can trigger cells to activate a cellular death pathway (Nature, 361:739-742, 1993), that several viruses encode proteins to block attempted cell suicide (Proc. Natl. Acad. Sci. 94: 690-694, 1997), that cellular anti-death genes can alter the pathogenesis of virus infections (Nature Med. 5:832-835, 1999) and of genetic diseases (PNAS. 97:13312-7, 2000) reflective of many human disorders. We have shown that anti-apoptotic Bcl-2 family proteins can be converted into killer molecules (Science 278:1966-8, 1997), that Bcl-2 family proteins interact with regulators of caspases and regulators of cell cycle check point activation (Molecular Cell 6:31-40, 2000). In addition, Bcl-2 family proteins have normal physiological roles in regulating mitochondrial fission/fusion and mitochondrial energetics to facilitate neuronal activity in healthy brains.

The J. Webster Stayman Lab studies both emission tomography and transmission tomography (CT, tomosynthesis and cone-beam CT). Our research activities relate to 3-D reconstruction, including model-based statistical / iterative reconstruction, regularization methods and modeling of imaging systems. We are developing a generalized framework for penalized likelihood (PL) reconstruction combining statistical models of noise and image formation with incorporation of prior information, including patient-specific prior images, atlases and models of components / devices known to be in the field of view. Our research includes algorithm development and physical experimentation for imaging system design and optimization.

Research in the James Fackler Lab explores the operational side of the hospital environment, seeking ways to optimize patient care and physician decision-making. Our work includes building a mathematical model of how patients move throughout a hospital, which we believe will help hospitals better predict the influx of emergency cases and therefore optimize resource preparation and scheduling of elective procedures. We also research data acquisition and data mining in the operating room and intensive care unit, with a goal of identifying patterns and trends.

The main research interests of the James Hamilton Lab are the molecular pathogenesis of hepatocellular carcinoma and the development of molecular markers to help diagnose and manage cancer of the liver. In addition, we are investigating biomarkers for early diagnosis, prognosis and response to various treatment modalities. Results of this study will provide a molecular classification of HCC and allow us to identify targets for chemoprevention and treatment. Specifically, we extract genomic DNA and total RNA from liver tissues and use this genetic material for methylation-specific PCR (MSP), cDNA microarray, microRNA microarray and genomic DNA methylation array experiments.

Research in the James Knierim Laboratory attempts to understand the flow of information through the hippocampal formation and the computations performed by the various subfields of the hippocampus and its inputs from the entorhinal cortex. To address these issues, we use multi-electrode arrays to record the extracellular action potentials from scores of well-isolated hippocampal neurons in freely moving rats. These neurons, or ""place cells,"" are selectively active when the rat occupies restricted locations in its environment and help to form a cognitive map of the environment. The animal uses this map to navigate efficiently in its environment and to learn and remember important locations. These cells are thought to play a major role in the formation of episodic (autobiographical) memories. Place cells thus constitute a tremendous opportunity to investigate the mechanisms by which the brain transforms sensory input into an internal, cognitive representation of the world and then uses this representation as the framework that organizes and stores memories of past events.

How do we see, hear, and think? More specifically, how can we study living people to understand how the brain sees, hears, and thinks? Recently, magnetic resonance imaging (MRI), a powerful anatomical imaging technique widely used for clinical diagnosis, was further developed into a tool for probing brain function. By sensitizing magnetic resonance images to the changes in blood oxygenation that occur when regions of the brain are highly active, we can make ""movies"" that reveal the brain at work. Dr. Pekar works on the development and application of this MRI technology. Dr. Pekar is a biophysicist who uses a variety of magnetic resonance techniques to study brain physiology and function. Dr. Pekar serves as Manager of the F.M. Kirby Research Center for Functional Brain Imaging, a research resource where imaging scientists and neuroscientists collaborate to study brain function using unique state-of-the-art techniques in a safe comfortable environment, to further develop such techniques, and to provide training and education. Dr. Pekar works with center staff to serve the center's users and to keep the center on the leading edge of technology.