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Kansas State University

EXTERNAL ADVISORY COMMITTEE



The external advisors are not only established investigators with expertise appropriate for the junior faculty, but also leaders in the discipline of epithelial physiology recognized for their achievements by receipt of international awards, journal editorships, and elected office in scientific societies and organizations. Junior faculty participants of this COBRE benefit greatly from mentoring and evaluation by these renowned scientists.

This is a photograph of Walter Boron   Dr. Walter Boron
  Professor and Chairman, Physiology & Biophysics
  Case School of Medicine, Case Western Reserve University
  Phone: 216-368-3400
  Fax: 216.368.5586
  e-mail: wfb2@case.edu

Dr. Walter Boron’s laboratory studies the ion-transport processes involved in regulation of intracellular pH (pHi), and how these transporters are themselves regulated by cell volume, hormones, and oncogenes. A variety of pH-sensitive microelectrodes and dyes (including digital imaging techniques) are used to monitor pHi in single cells (e.g., neurons, glia, muscle, mesangial cells, osteoclasts, and cells of perfused renal tubules, gastric glands and colonic crypts). The primary objective is to deduce mechanisms by which acids and bases are transported across membranes, how the transporters are regulated, and how pHi changes affect processes such as growth control, transepithelial acid-base transport, and the tone of vascular smooth muscle. The laboratory is also attempting to clone the genes for bicarbonate transport proteins.

 


This is a photograph of Robert Bridges   Dr. Robert Bridges
  Professor and Chair of Physiology and Biophysics
  Rosalind Franklin University of Medicine and Science
  Phone: (847)-578-3273
  Fax: 847-578-3265
  e-mail: bob.bridges@rosalindfranklin.edu

Dr. Robert Bridges' primary area of research is on epithelial ion transport with a special focus on epithelial ion channels. His lab uses a wide range of electrophysiological methods and video imaging to study the regulation, pharmacology and biophysics of ion channels including CFTR, ENaC and various potassium channels. He collaborates with several pharmaceutical companies working toward the development of drugs for the treatment of Cystic Fibrosis and Chronic Obstructive Pulmonary Disease.

 



This is a photograph of Eric Delpire   Dr. Eric Delpire
  Professor of Anesthesiology
  Professor of Molecular Physiology and Biophysics
  Vanderbilt University Medical Center
  Phone: 615)-343-7409
  Fax: (615)-343-3916
  e-mail: eric.delpire@vanderbilt.edu

Dr. Eric Delpire’s research topics include the physiology of electroneutral cation-chloride cotransporters, regulation of intracellular chloride in neurons and GABAergic neurotransmission. GABAergic neurotransmission depends upon the transmembrane Cl concentration gradient that exists at the synapse. The intracellular Cl concentration in CNS and PNS neurons is regulated, in part, by cation-chloride cotransport mechanisms such as Na-K-2Cl and K-Cl cotransporters. For example, the inward Na-K-2Cl cotransporter is highly expressed in immature CNS neurons, resulting in a high intracellular Cl- concentration and GABA depolarizing or excitatory responses. In contrast, mature CNS neurons have low Na-K-2Cl cotransporter and high K-Cl cotransporter activity, leading to low intracellular Cl- and hyperpolarizing or inhibitory GABA responses. His laboratory is creating knockouts of the cotransporters and studying their relationship with neurotransmission and behavior. His work, in collaboration with Drs. Robert MacDonald and Mike McDonald, involves molecular biology, physiology, electrophysiology and behavior. These studies have significance in perception of pain, hyper-excitability and epilepsy, nerve conduction, peripheral neuropathy and paraplegia.



This is a photograph of Shmuel Muallem  Dr. Shmuel Muallem
  Chief, Epithelial Signaling and Transport Section
  Molecular Physiology and Therapeutics Branch
  NIDCR, Building 10, Room 1N-113
  NIH, Bethesda MD 20892
  Phone: (301)-496-1363
  e-mail: shmuel.muallem@nih.gov

Dr. Shmuel Muallem's research involves regulation of fluid and electrolyte secretion by epithelial cells. A key protein regulating epithelial function is the Cystic Fibrosis Transmembrane Regulator (CFTR). Dr. Muallem's work is geared towards understanding how CFTR regulates the activity of other transport proteins, in particular HCO3- transport across the luminal membrane. He believes that defective regulation of HCO3- transport is a critical problem in Cystic Fibrosis patients. Another aspect of his work is the study of the function of Ca2+ transport and signaling proteins and their organization into complexes. Electrophysiological and confocal imaging techniques are used to monitor Ca2+ in subcellular compartments and follow the activity of Ca2+ pumps and Ca2+ channels. These approaches are complemented by a variety of biochemical and molecular techniques to study the organization of Ca2+ signaling complexes in microdomains of polarized cells.

 


This is a photograph of Hanno Steen  Dr. Hanno Steen
  Director of the Proteomics Center, Children's Research Hospital Boston
  Assistant Professor, Department of Pathology
  Phone: (617)-919-2629
  Fax: (617)-730-0168
  e-mail: hanno.steen@childrens.harvard.edu

Dr. Hanno Steen is a pioneer in developing methods for the qualitative and quantitative analysis of protein modifications of complex protein mixtures by mass spectrometry, with special emphasis on tyrosine phosphorylation. In carcinogenesis, the pivotal role of tyrosine phosphorylation is underscored by the notion that almost half of the oncogenes known to date encode tyrosine kinases. Additional goals include: 1) development of methods for identifying and quantifying various protein modifications that are involved in pediatric diseases in order to provide new insights into the underlying biological processes, a prerequisite for a rational approach to prevent and/or cure these diseases. 2) screening to detect and identify diagnostic and prognostic disease markers in body fluids, which offer an easily accessible mirror of the state of the entire body. These biomarkers can guide treatment decisions, predict patient phenotypes, and allow for early diagnosis.

 


FORMER EXTERNAL ADVISORY COMMITTEE (2002-2007)



The external advisors are not only established investigators with expertise appropriate for the junior faculty, but also leaders in the discipline of epithelial physiology recognized for their achievements by receipt of international awards, journal editorships, and elected office in scientific societies and organizations. Junior faculty participants of this COBRE benefit greatly from mentoring and evaluation by these renowned scientists.

This is a photograph of Seth Alper  Dr. Seth Alper
  Professor of Medicine
  Beth-Israel Deaconess Medical Center, Harvard University
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The Alper laboratory studies the molecular basis of transmembrane and transepithelial ion transport, with foci on the ion exchange, ion co-transport, and channel mediated conductive transport of chloride, bicarbonate, and potassium. The laboratory is recognized for cloning variant transcripts from each of the three genes of the band-3 anion exchanger family. The physiological role of these polypeptides is being evaluated in intact animals subject to perturbations of acid-base status and extra-cellular fluid volume. Ongoing work also addresses the molecular pharmacology of K+ channel targets in sickle cell disease, secretory diarrhea, and polycystic kidney disease.





This is a photograph of Klaus Beyenbach   Dr. Klaus Beyenbach
  Professor of Physiology, Department of Biomedical Sciences
  Cornell University

Dr. Beyenbach’s laboratory studies the mechanisms and regulation of epithelial transport, and significant aspects of renal function such as aglomerular urine formation, transport across insect malpighian tubules, and mechanisms of magnesium homeostasis. Dr. Beyenbach and his research group are adept at the use of sophisticated electrophysiological techniques to define transport pathways in micro-preparations. The laboratory is internationally recognized for their work defining novel ion transport and fluid secretion mechanisms.





This is a photograph of Walter Boron  Dr. Walter Boron
  Professor and Chairman, Physiology & Biophysics
  Case School of Medicine, Case Western Reserve University

Dr. Walter Boron’s laboratory studies the ion-transport processes involved in regulation of intracellular pH (pHi), and how these transporters are themselves regulated by cell volume, hormones, and oncogenes. A variety of pH-sensitive microelectrodes and dyes (including digital imaging techniques) are used to monitor pHi in single cells (e.g., neurons, glia, muscle, mesangial cells, osteoclasts, and cells of perfused renal tubules, gastric glands and colonic crypts). The primary objective is to deduce mechanisms by which acids and bases are transported across membranes, how the transporters are regulated, and how pHi changes affect processes such as growth control, transepithelial acid-base transport, and the tone of vascular smooth muscle. The laboratory is also attempting to clone the genes for bicarbonate transport proteins.



This is a photograph of Dennis Brown  Dr. Dennis Brown
  Associate Chief for Research Affairs, MGH Nephrology Division
  Director, MGH Program in Membrane Biology
  Professor of Medicine, Harvard Medical School

Dr. Brown’s research is directed towards understanding the cell biological mechanisms that regulate polarized membrane protein trafficking and vesicle transport in epithelial cells. He has focused on vasopressin-induced translocation of the aquaporin 2 water channel both in vivo and in transfected cell culture systems, and on the recycling of the vacuolar H+ATPase in specialized proton-transporting cells in the kidney and, more recently, in the male reproductive tract. His work uses a combination of morphological, immunocytochemical, cell biological, and molecular biological approaches to address issues related to the role of protein kinases, the cytoskeleton and GTP-binding proteins in the exocytosis and endocytosis of these functionally important plasma membrane proteins.



This is a photograph of David Dawson   Dr. David Dawson
  Professor and Chair of Physiology and Pharmacology
  Oregon Health and Science University

The goal of the research carried out in Dr. Dawson's lab is to provide the scientific basis for the development of drugs that can be used to treat these two lethal diseases of childhood. The research combines high-resolution electrophysiological measurements of CFTR behavior with chemical modification strategies designed to reveal what parts of the CFTR molecule are most important for its vital functions. This information is used to refine atomic scale models for the protein. Understanding how this complex molecule does its job will provide the foundation for the design of drugs or other therapies that can be used to increase the activity of CFTR in cystic fibrosis patients or to decrease the activity of CFTR in people suffering from secretory diarrhea.



This is a photograph of Nancy Wills   Dr. Nancy Wills
  Professor of Neuroscience and Cell Biology
  The University of Texas Medical Branch

Work on her laboratory is focused on epithelial cell physiology, most recently the retinal pigment epithelium (RPE). This important layer of cells is located adjacent to the photoreceptors of the retina and performs functions that are crucial for photoreceptor survival. Among the vital homeostatic processes performed by the RPE are the transport of ions, inorganic solutes, and water to and from the subretinal space surrounding the photoreceptors. Disruptions of RPE ion and fluid transport can result in macular edema, retinal detachment, and degeneration of the neural retina. Ion channels mediate membrane ion movements that contribute to transepithelial ion and fluid transport mechanisms. Her laboratory uses molecular biology, electrophysiology, cell culture, and optical techniques to understand the factors that regulate ion channel activity and their role in age-related diseases, including macular degeneration, and other retinal diseases. Work is currently underway to delineate how oxidative stress modulates channel activity, channel expression, and gating.