Investigators in the Pablo Iglesias Lab use analytic tools from control systems and dynamical systems to study cell biology, including biological signal transduction pathways. Our research interests include the ways cells interpret directional cues to guide their motion, regulatory mechanisms that control cell division, and the sensing and actuation that enable cells to maintain lipid homeostasis.

The Wong Lab seeks to understand mechanisms employed by cells and tissues to maintain metabolic homeostasis. We are currently addressing how adipose- and skeletal muscle-derived hormones (adipokines and myokines), discovered in our lab, regulate tissue crosstalk and signaling pathways to control energy metabolism. We use transgenic and knockout mouse models, as well as cell culture systems, to address the role of the CTRP family of hormones in physiological and disease states. We also aim to identify the receptors that mediate the biological functions of CTRPs.

The James Hamilton laboratory performs pre-clinical experiments and basic studies investigating liver inflammation, fibrosis, and nuclear receptor signaling. In close collaboration with Dr Svetlana Lutsenko in Physiology, their team performs detailed studies of hepatocyte and non-parenchymal cell isolation, culture, biology and genetic manipulation. Working with models of Wilson disease, a disorder of copper overload, they discovered that hepatic nuclear receptor mediated control of lipid metabolism is a preferential and early target of copper toxicity. Furthermore, targeting nuclear receptors with pharmacologic agonists prevents and reverses liver inflammation and fibrosis.

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 research in the Svetlana Lutsenko Laboratory is focused on the molecular mechanisms that regulate copper concentration in normal and diseased human cells. To understand the molecular mechanisms of copper homeostasis in normal and diseased human cells, we utilize a multidisciplinary approach involving biochemical and biophysical studies of molecules involved in copper transport, cell biological studies of copper signaling, and analysis of copper-induced pathologies using Wilson's disease gene knock-out mice.

Researchers in the Suzanne Jan de Beur Lab are interested in bone and mineral metabolism, endocrinology and osteoporosis. In addition, we focus on hormonal regulators of phosphate homeostasis, parathyroid hormone signaling and the molecular basis of hypophosphatemic disorders.

The Melia lab performs basic, translational, and clinical research on inflammatory bowel disease. Specifically, Dr Melia's basic science and translational research program is concentrated on novel roles of manganese (Mn) homeostasis in Crohn's disease and the interaction with aberrant N-glycosylation with current support from NIDDK and NICHD, including support as a co-investigator in the Center for Metals in Nutrition and Development.

The Gregg Semenza Lab studies the molecular mechanisms of oxygen homeostasis. We have cloned and characterized hypoxia-inducible factor 1 (HIF-1), a basic helix-loop-helix transcription factor. Current research investigates the role of HIF-1 in the pathophysiology of cancer, cerebral and myocardial ischemia, and chronic lung disease, which are the most common causes of mortality in the U.S.

Work in the Enid Neptune Lab focuses on topics within the fields of pulmonary and critical care medicine. Our research centers primarily on therapeutic strategies for Marfan syndrome and hepatocyte growth factor signaling in airspace homeostasis. We also conduct research on chronic obstructive pulmonary disease (COPD), with a focus on its mechanisms and potential methods for preventing its progression. Our research within critical care has most recently involved investigating superoxide dismutase 3 dysregulation in neonatal lung injuries.

The Espenshade Lab uses a multi-organismal and multidisciplinary approach to understand how eukaryotic cells measure insoluble lipids and dissolved gases. We have chosen cholesterol and oxygen as our model molecules, based on their essential roles in cell function and the importance of their proper homeostasis for human health.