Our Distinguished Faculty

The research interests of the faculty in the Department of Physiology and Biophysics are very diverse, including systems and cellular physiology, cell and molecular biology, biophysics, and structural biology. A common thread that links our faculty is an emphasis on quantitative understanding of biological process on a physical level. The department has particular strengths in membrane biophysics, cellular signal transduction, inter-cell communication, lipid metabolism, vision, cardiac electrophysiology, neuroscience, and the regulation of cell growth and differentiation.
On the following pages, we highlight the work of each professor. For more details on their research groups and ongoing projects, please visit our Web site at www.pnb.sunysb.edu.

PETER BRINK, Professor and Chairman
Ph.D. 1976, University of Illinois
Peter Brink uses dual whole cell patch clamp and dual permeabilized patch clamp to monitor gap junction channel gating/permselectivity under defined ionic conditions and more relevant physiological conditions: the effects of various messenger molecules on gating of gap junction are studied in detail with these approaches. Any individual gap junction channel is composed of 12 subunit proteins known as connexins. Because the primary sequence of a number of connexins has been elucidated, this has allowed for the transfection of cells devoid of gap junctions to be used to study pure populations of specific connexin-derived gap junctions, as well as mutants generated via site-directed mutagenesis. Brink uses N2A mouse neuroblastoma cells as host cells for the transfection of wild-type and mutant connexins. Dual whole cell patch clamp is then used to monitor the gating and preselective properties of the various expressed connexins. In one example, Brink uses two models, which result in dry-eye in mice. These efforts center on elucidating the mechanism of fluid transport across the epithelium that makes up the secretory portion of these lacrimal glands. His results from patch clamping cells isolated from these animals indicate that diseased mice lack the necessary number of K channels and possess an increased number of Cl- and cation channels resulting in membrane depolarization and compromised transepithelial transport.
(631) 444-3124, peter@patch.pnb.sunysb.edu


Mark E. Bowen, Assistant Professor
Ph.D. 1998, University of Illinois at Chicago
Prof.Bowen is interested in understanding the molecular underpinnings of synaptic transmission. The regulated communication between neurons underlies all that makes us human: learning, memory and emotion. When communication goes awry the result is mental illness, neurodegenerative disease and death. By understanding the molecular basis for these conditions, pharmaceutical strategies for intervening become possible.
Synaptic state is controlled by the post synaptic density, a signal processing machine containing hundreds proteins including cytoskeletal elements, receptors, ion channels and their associated signaling proteins. His lab focuses on the MAGUK (Membrane Associated GUanlyate Kinase) family of scaffolds that localize and organize glutamate receptor signaling. Great progress has been made in identifying proteins at the synapse and in studying their binary interactions. His lab seeks to extend this knowledge by studying the structure and dynamics of multiprotein complexes reconstituted from purified components. To sort out the heterogeneity in these complex mixtures, They use single molecule fluorescence microscopy to follow individual complexes.
They aim to understand how MAGUK proteins regulate the availability of binding sites through structural rearrangement, and determine how MAGUK binding partners interact with each other in higher order complexes. Scaffold proteins are hubs in the network of protein interactions. By learning the relative weights of interactions at the scaffold, They will come closer to predicting the output of this network.

Chris Clausen, Associate Professor
Ph.D. 1979, University of California at Los Angeles
Chris Clausen’s laboratory group is studying the regulation of proton transport in renal epithelia, the role of endo- and exocytotic processes in altering rates of ion transport, and mechanisms involved in epithelial sodium, chloride, and glucose transport. Experimental techniques include analysis of epithelial electrical impedance, transepithelial and intracellular electrophysiological recordings, measurements of uptake and release of fluid-phase makers, fluorescence microscopy, whole-cell patch-clamp studies, morphometric analyses, and computer modeling.
The lab has also developed computer models of ionic currents in Purkinje fibers and ventricular myocytes to compute space-clamped and propagating action potentials. The models are used to investigate antiarrhythmic drug action and to model arrhythmias, notably early-after depolarizations and re-entrant arrhythmias.
(631) 444-3042, Chris.Clausen@stonybrook.edu

 

IRA S. COHEN, Leading Professor
M.D., Ph.D. 1974, New York University
The research in Ira Cohen’s laboratory focuses on cardiac electrical activity. Using a combination of biophysical (patch clamp) and molecular (message distribution) techniques, the laboratory investigates both normal and abnormal (arrhythmogenic) electrical activity. A major focus of the laboratory is to assign to each cardiac membrane current a molecular correlate and to understand how second messenger systems regulate the properties of ion channels. Recent projects in the laboratory include the study of primary and secondary pacemakers and the membrane currents that control the action potential duration.
(631) 444-3043, Ira.Cohen@stonybrook.edu

James P. Dilger, Professor
Ph.D. 1980, Stony Brook University
James Dilger is Associate Professor of Anesthesiology with a joint appointment in Physiology and Biophysics. His research deals with ligand-gated ion channels in nerve and muscle cells. His laboratory studies the structure and function of channels using patch clamp current recording techniques. A method of rapidly perfusing excised patches on the submillisecond time scale was developed in his lab. This provides a controlled way to examine channel activation as it occurs during rapid synaptic transmission. These tools are applied to questions of the molecular actions of anesthetic and muscle-relaxant drugs. Although general anesthetics have been in clinical use for more than 150 years, the ways in which they cause unconsciousness, analgesia, and amnesia remain unknown. Ligand-gated ion channels are likely targets of anesthetics. Work in Dilger’s lab involves determining sites and mechanisms of action of these drugs.
(631) 444-3458, jdilger@epo.som.sunysb.edu

MOISÉS EISENBERG, Associate Professor
Ph.D. 1972, California Institute of Technology
Department of Pharmacological Sciences
Research interests in Moisés Eisenberg’s group revolve around computational approaches to structural biology. Elucidation of three-dimensional structures of biological macromolecules whose primary structure is known using computer-assisted molecular mechanics and dynamics is now possible if additional experimental data is available; for example, inter-atomic distances derived from nuclear magnetic resonance, or sequence analogy to previously known structures in genetically related families, both of which were used in Eisenberg’s computer laboratory. By applying these methods, the group continues to build up a library of structures of DNA molecules containing a variety of well-defined chemical lesions of biomedical significance, and those of complexes between these damaged DNA molecules and the enzymes they bind to, involved in DNA repair and replication. Prediction of the precise docking conformation between pairs of biomolecules of known structures has been partially validated and continues to be investigated.
(631) 444-3064, Moshe@uhmc.sunysb.edu

 

M. Raafat El-Maghrabi, Research Associate Professor
Ph.D. 1978, Wake Forest University
Research in Raafat El-Maghrabi’s laboratory deals with two facets of metabolic regulation of gene expression. First, delineating the factors involved in regulating expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase genes; the products of these genes are responsible for modulating rates of glycolysis in almost all cell types. For example, a novel form of the enzyme is overexpressed in brain tumor cell lines, and the lab is investigating the factors responsible for the activation of the gene. The studies involve mapping of the regulatory regions of the genes with respect to transcription factor and hormonal binding sites. The lab also deals with the structure/function relationships of the products of these genes, the enzymes themselves, with respect to reciprocal regulation of the two opposing activities by phosphorylation, and the interaction of the two domains. These studies involve expression of wild type and mutated forms of the enzyme using bacterial expression systems and kinetic and structural analysis of the various forms.
(631) 444-3049, Raafat.El-Maghrabi@stonybrook.edu

 

ARTHUR P. GROLLMAN, Professor
M.D. 1959, Johns Hopkins University
Department of Pharmacological Sciences, School of Medicine
Arthur Grollman’s Laboratory of Chemical Biology focuses on the biological consequences of DNA damage with particular reference to molecular mechanisms of DNA replication, mutagenesis, and DNA repair. Site-specific methods are used to explore the mutagenic potential of defined DNA lesions in mammalian cells. Shuttle plasmid vectors are used to establish the efficiency and fidelity of translesional synthesis. Reactions, catalyzed by DNA polymerases, permit mutational events to be studied in vitro. The three-dimensional structure of damaged DNA is used to correlate molecular structure and biological function. This multidisciplinary approach permits Grollman and his students to elucidate the molecular basis of mutagenic specificity. Oxidative DNA damage is a major contributor to spontaneous mutagenesis, carcinogenesis, and the aging process. Grollman’s lab has determined the miscoding effects of DNA damage produced by reactive oxygen species and has defined an error-avoidance pathway that protects cells against mutations produced by 8-oxoguanine. DNA N-glycosylases and AP-lyases are central to this process. Genes for these enzymes have been cloned and the lab uses gene knockout technology to analyze the effects of repair of oxidatively damaged DNA in transgenic mice.
(631) 444-3080, apg@pharm.sunysb.edu

 

YAACOV HOD, Associate Professor of Research
Ph.D. 1977, Technion, Israel Institute of Technology
Department of Urology
The main research work of Yaacov Hod focuses on the control of gene expression at the level of mRNA stability. As a model system, Hod uses the gene encoding the gluconeogenic enzyme P-enolpyruvate carboxykinase (PEPCK), whose expression is regulated by several hormones including glucagon (acting via cAMP), insulin, and glucocorticoids. In previous studies, Hod has demonstrated that cAMP enhances PEPCK gene expression both by inducing the transcription rate of the gene, as well as by stabilizing the mRNA against degradation. In an effort to elucidate the mechanism by which cAMP regulates mRNA stability, Hod has isolated a novel protein (RBP) with an RNA-binding activity whose activity is regulated via protein-protein interaction. Current studies focus on establishing the exact cellular role of the RBP and its regulation, employing a variety of approaches in molecular and cellular biology. Recent studies have identified the gene in a chromosomal region showing a large number of chromosomal aberrations in several tumors. The possible involvement of RBP in cancer is another goal of Hod’s studies.
(631) 444-3721, yhod@mail.som.sunysb.edu

 

CHRIS JACOBSEN, Associate Professor
Ph.D. 1988, Stony Brook University
Department of Physics and Astronomy
Chris Jacobsen carries out research in X-ray optics and microscopy. This involves a collaboration with Bell Labs on soft X-ray zone plates that produce the finest focus of electromagnetic radiation of any wavelength and research at a soft X-ray undulator beamline at nearby Brookhaven National Laboratory for which he is the spokesperson. His interests include X-ray optics and imaging theory, X-ray instrumentation, and application of these methods, such as tomographic imaging and spectromicroscopy, to problems in biology and environmental science. He is the recipient of a Presidential Faculty Fellow Award (National Science Foundation/White House, 1992-1997), the International Dennis Gabor Award for research in optics, and the Outstanding Young Scientist Award of the Microbeam Analysis Society.
(631) 632-8903, Chris.Jacobsen@stonybrook.edu

 

ROGER JOHNSON, Professor
Ph.D. 1968, University of Southern California
The laboratory of Roger Johnson investigates the regulation of adenylyl cyclases by 3'-nucleotides. This family of enzymes catalyzes the formation of adeno-sine 3':5'-monophosphate (cAMP) from 5'ATP and constitutes a major trans-membrane signal transduction system. One approach of the laboratory has been to synthesize and use biochemical probes to define structural characteristics of the inhibitory configuration of the enzyme. These are used in conjunction with molecular biological approaches to facilitate the identification of nucleotide binding sites within native and recombinant wild type and mutated forms of the enzymes. Experiments use standard techniques for chemical and proteolytic fragmentation and sequence analysis as well as time-of-flight MALDI (Matrix-Assisted Laser Desorption Ionization) mass spectrometry that allows sequencing of intact peptides. The overall intent of the research is to describe structure-function relationships within the adenylyl cyclase family and to define the new regulatory links between this family of enzymes and nucleic acid metabolism.
(631) 444-3040, Roger.Johnson@stonybrook.edu

 

LEEMOR JOSHUA-TOR, Associate Professor
Ph.D. 1991, The Weizmann Institute of Science
Cold Spring Harbor Laboratory
Leemor Joshua-Tor studies the molecular basis of cell regulatory processes in terms of molecular recognition. In her research, her lab uses tools of structural biology and biochemistry in a combined approach to look at proteins, protein complexes, and protein-nucleic acid complexes associated with these processes. Through X-ray crystallography, an accurate three-dimensional structure of individual proteins, their complexes, and the interactions in which they are involved are determined. The lab uses biochemistry to study properties predicted by protein structure and use information from molecular biology and genetics in collaborative efforts to study protein function.
Joshua-Tor’s current efforts center on two distinct themes. The first involves structural studies of complexes involved in DNA regulatory processes (replication and transcription). The second is concerned with the regulation of proteolysis in processes, such as apoptosis and in an evolutionarily conserved family of self-compartmentalizing intracellular proteases, the bleomycin hydrolases. With the bleomycin hydrolases, the lab is also investigating the structural basis for tumor cell drug resistance to bleomycin and the link to Alzheimer’s disease.
(516) 367-8821, leemor@cshl.org

 

JANOS KIRZ, Distinguished Professor
Ph.D. 1963, University of California at Berkeley
Department of Physics and Astronomy
Janos Kirz is interested in soft X-ray optics, coherence properties, the physics of the interaction of soft X-rays with matter, and the applications of these topics to microscopy and spectromicroscopy. He and his students were the first to create a fine focused probe of soft X-rays using zone plates and to use this probe to build a scanning microscope. Kirz started his professional life in high energy physics, with experiments in Berkeley, Brookhaven National Laboratory (BNL), CERN, SLAC, and Fermilab. His more recent work with X-rays is centered on the X1 undulator at BNL’s National Synchrotron Light Source. He was the recipient of a Sloan and a Guggenheim Fellowship, as well as the Chancellor’s Award for Excellence in Teaching. Between 1998 and 2001, Kirz served as Chair of the Department of Physics and Astronomy.
(631) 632-8106, Janos.Kirz@stonybrook.edu

IRVIN B. KRUKENKAMP, Professor
M.D. 1982, University of Maryland
Department of Surgery
In 1997, Irvin Krukenkamp joined the Stony Brook faculty as professor of surgery and chief of cardiothoracic surgery. Coming from Harvard University, Krukenkamp now directs the Division of Cardiothoracic Surgery, and also co-directs the newly formed Heart Hospital. Performing the only open heart surgery in Suffolk County, he and his team of cardiothoracic surgeons specialize in high-risk and tertiary care types of surgical intervention. Krukenkamp’s special clinical interests also include coronary and valve surgery in the octogenarian, and operative management and myocardial protection of the profoundly dysfunctional heart.
Krukenkamp’s research interests include myocardial mechanics and energetics, myocardial protection by cardioplegia, and new endogenous myoprotective strategies utilizing preconditioning. He is currently the principal investigator or co-investigator of three NIH-funded studies focusing on myocardial protection in the senescent heart, the electrophysiology of potassium channel opening, and the mechanics of ischemic myocardial preconditioning.
(631) 444-1820, Irvin.Krukenkamp@stonybrook.edu

 

WILLIAM LENNARZ, Professor and Chair
Ph.D. 1959, University of Illinois
Department of Biochemistry and Cell Biology
William Lennarz is interested in understanding several steps involved in glycoprotein synthesis, including N-glycosylation and protein folding, as well as the functions of the glycan chains. He uses yeast, a simple eukaryotic organism that can be genetically manipulated, to study glycoprotein assembly. More specifically, he investigates the enzymatic processes of oligosaccharide addition and removal that occur in nascent polypeptides and misfolded glycoproteins, respectively. In addition, Lennarz is studying the enzyme that catalyzes folding and disulfide bond formation in glycoproteins.
(631) 632-8560, William.Lennarz@stonybrook.edu

 

ERWIN LONDON, Professor
Ph.D. 1980, Cornell University
Department of Biochemistry and Cell Biology
Erwin London’s interests involve membrane structure and function. One focus is understanding how proteins translocate across membranes using diphtheria toxin. The structure of this toxin within membranes and its translocation is being studied using site-directed mutagenesis to introduce fluorescence labels within the toxin molecule. Understanding translocation should have important implications for the design of therapeutic agents and vaccines for bacterial infections. In a second project, London is determining the relationship between amino acid sequence and structure using synthetic transmembrane helices. Their structure and location within the lipid bilayer is analyzed using fluorescence quenching, circular dichroism, and other spectroscopic techniques. The aim is to reveal the rules governing membrane protein folding. London’s third project involves exploring the function of lipid domains enriched in cholesterol and sphingolipid. These domains are believed to play a role in signal transduction, viral and toxin entry into cells, protein sorting among organelles, and prion formation. His aim is to determine the principles that induce formation of these domains and regulate their lipid and protein composition.
(631) 632-8564, Erwin.London@stonybrook.edu

 

Richard Mathias, Professor
Ph.D. 1975, University of California at Los Angeles
Many physiological properties of a tissue are the integrated result of the physical properties of structure, electrical and diffusional interconnection of cells within the tissue, and specific membrane properties of each cell type. Richard Mathias is interested in how these three factors interact to produce the functional tissue properties. His laboratory is working on various types of mammalian cardiac tissue, where the function is primarily regulation of excitability and contraction. Mathias and his team are working on the lens of the eye, where function requires crystalline clarity. Experimental techniques include the following: intracellular microelectrode studies of tissue impedance, voltage clamp; membrane patch-clamp; ion selective microelectrodes, digital video microscopy; cloning and expression of membrane transport proteins; and modeling of forces/flows (e.g., voltage/current, pressure/fluid flow, concentration/diffusion, etc.) in tissues of complex anatomy.
(631) 444-3041, Richard.Mathias@stonybrook.edu

 

GARY G. MATTHEWS, Professor
Department of Neurobiology and Behavior
Ph.D. 1975, University of Pennsylvania
After postdoctoral research at the University of Colorado Medical School and Stanford University, Gary Matthews came to the Department of Neurobiology and Behavior at Stony Brook in 1981. The Matthews laboratory uses biophysical and molecular biological techniques to study mechanisms of cellular communication.
(631) 632-9784, Gary.G.Matthews@stonybrook.edu

 

DAVID McKINNON, Associate Professor
Ph.D. 1987, Australian National University
Department of Neurobiology and Behavior
David McKinnon’s research focuses on how the electrophysiological phenotype of excitable cells is established and maintained in vivo. The electrophysiological phenotype is actively maintained by a combination of physiological inputs and tropic signals and can be modified by changes in the nature of these inputs. One aim of the lab is to identify the physiological signals that regulate ion channel gene expression in vivo. Experimental work has concentrated on voltage-gated potassium channels since the primary function of most of these channels is to control the firing properties of excitable cells. To identify which channels contribute to the final differentiation of firing properties, the McKinnon lab has combined two different techniques. Voltage-gated potassium channels have been studied using electrophysiological techniques. In addition, the lab has used molecular biology techniques to clone a large number of novel, mammalian potassium-channel cDNAs. The research concentrates on two separate systems: sympathetic neurons and cardiac myocytes.
(631) 444-7334, David.McKinnon@stonybrook.edu

 

STUART McLAUGHLIN, Professor
Ph.D. 1968, University of British Columbia
Stuart McLaughlin is a biophysicist interested in signal tranduction. His laboratory studies how physical factors (e.g., electrostatics, reduction of dimensionality) choreograph the diffusional dance of information through the calcium/phospholipid second messenger system. Both theoretical and experimental approaches are used. For example, single molecule enzymology studies are being conducted with a phospholipase C enzyme (PLC) of known structure by combining laser tweezers and microelectrophoresis. PLC hydrolyzes the lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to produce two second messengers that activate protein kinase C (PKC). The Poisson-Boltzmann equation is solved for realistic atomic models of phospholipid bilayer membranes and the major PKC substrate, MARCKS, in an attempt to understand how MARCKS sequesters PIP2, then releases the lipid upon phosphorylation by PKC, a phenomenon known as the myristoyl-electrostatic switch.
(631) 444-3615, smcl@epo.som.sunysb.edu

 

LORNE M. MENDELL, Distinguished Professor
Ph.D. 1965, Massachusetts Institute of Technology
Department of Neurobiology and Behavior
Lorne Mendell’s research examines the cellular mechanisms of neuronal plasticity in the mammalian spinal cord. He is currently investigating mechanisms by which neurotrophin molecules, such as nerve growth factor (NGF), modify activity of neural circuits mediating transmission of nociceptive stimuli and muscle stretch. He is also interested in the application of neurotrophins to the recovery of function after neural injury. Mendell served as President of the Society for Neuroscience in 1997-1998, and is Chair of the Department of Neurobiology and Behavior.
(631) 632-8616, Lorne.Mendell@stonybrook.edu

W. TODD MILLER, Professor
Ph.D. 1989, Rockefeller University
Department of Physiology and Biophysics
The focus of research in Todd Miller’s laboratory is the specificity of signaling by
tyrosine kinases. These enzymes play a central role in regulating the growth of
normal cells, and constitutive activation of tyrosine kinases can lead to the development and progression of cancer. The major research goals of the laboratory are: to understand how tyrosine kinases recognize their target proteins in cells, to determine how these enzymes are regulated in normal cells, and to develop strategies to block the action of oncogenic tyrosine kinases. The laboratory primarily uses biochemical strategies to investigate tyrosine kinase structure and function.
(631) 444-3533, miller@physiology.pnb.sunysb.edu

 

Leon C. Moore, Professor
Ph.D. 1976, University of Southern California
The major ongoing research interest of Leon Moore’s lab is the physiology and pathophysiology of the renal microcirculation. At present, the mechanisms responsible for vascular dysfunction and vascular and glomerular injury in chronic renal failure (CRF) are being investigated. Among the factors that may contribute to the loss of normal vascular reactivity in CRF are low bioavailability of insulin-like growth factor I, rarefaction of the perivascular sympathetic nerves, and abnormalities in endothelial cell nitric oxide production. This work involves long-term animal studies, perfusion of renal arterioles in vitro, histochemical studies, and electrochemical measurement of NO release from renal arteries. Moore’s lab is also interested in the nonlinear dynamics of the tubuloglomerular feedback system. This system is an important controller of renal function. It displays periodic limit-cycle oscillations and, in some disease states, chaotic fluctuations. The work involves theoretical analyses, computer simulations, and experimental studies.
(631) 444-3047, moore@physiology.pnb.sunysb.edu

 

Nicolas Nassar, Research Assistant Professor
Ph.D. 1992, University Joseph Fourier
GTP-binding proteins play crucial roles in transmitting cellular signals that are initiated at the plasma membrane by the activation of various receptors. The proper spatial and temporal regulations of these proteins are essential for the good functioning of the cell, whereas mutations that impair GTP-hydrolysis lead to cellular pathways that are constitutively activated. Ras, which serves as a prototype for the small GTP-binding proteins, is found, for example, mutated at two hot spots in 30% of human cancers.

Current work in Nicolas Nassar’s laboratory focuses on the understanding of the protein-protein and protein-phospholipid interactions that govern the regulation of the Ras-like proteins. X-ray crystallography and other biophysical techniques are used to unravel the molecular details of the protein complexes that are at the heart of signaling pathways. Atomic models are in turn used to design inhibitors that might be developed as drugs to fight the proliferation of human cancers.
(631) 444-3521, Nicolas.Nassar@stonybrook.edu

 

DANIEL P. RALEIGH, Professor
Ph.D. 1988, Massachusetts Institute of Technology
Department of Chemistry
Daniel Raleigh’s research is centered on three complementary topics: studies of protein folding, the role of improper protein folding in human disease, and protein design. An understanding of how proteins fold is one of the major unsolved problems of modern biochemistry. The last few years have seen an explosion of interest in the protein-folding problem. New theoretical approaches and new experimental methods have been developed and applied to a variety of interesting systems. These developments coupled with the growing realization that protein misfolding plays an important role in a number of human diseases has fueled continued interest in this area. His investigations of protein misfolding are directed towards understanding the basis for the pathological aggregation of polypeptide hormones in certain diseases. Work on protein design is centered on methods to rationally improve the properties of proteins. Raleigh’s research involves a wide range of techniques, including but not limited to peptide synthesis, protein chemistry and molecular biology, multidimensional NMR, rapid kinetic measurements, and computational studies.
(631) 632-9547, Daniel.Raleigh@stonybrook.edu

 

MARIO J. REBECCHI, Research Associate Professor
Ph.D. 1984, New York University
Departments of Anesthesiology and Physiology and Biophysics
The aim of Mario Rebecchi’s research is to understand how the catalytic activities of intracellular phospholipases are controlled, particularly those that hydrolyze inositol lipids. Artificial and biological membranes and soluble substrate analogs are employed in the study phosphoinositide-specific phospholipase C (PLC) and its regulatory proteins. The roles of lipid packing and surface potentials on PLC adsorption, penetration, and activity are under investigation. A combination of physical, chemical, and molecular biological techniques are employed to understand how these enzymes adsorb to membrane surfaces and to identify those features of the protein important to processive catalysis at the membrane/solution interface. Of special interest are the distribution and dynamics of PLC and its substrate in living cells, which are studied by fluorescence microscopy using the latest imaging technology.
(631) 444-8178, rebecchi@epo.hsc.sunysb.edu

CLINTON T. RUBIN, Director of the Program in Biomedical Engineering and Professor
Ph.D. 1983, Bristol University
Departments of Anatomy, Bioengineering, and Orthopaedics
The focus of Clinton Rubin’s work is aimed at understanding the cellular mechanisms responsible for the growth, healing, and homeostasis of bone. More specifically, he is interested in how biophysical stimuli (i.e., mechanical, electrical, temperature, magnetic, pressure) mediate these responses. The clinical significance of this work is applicable to the inhibition of osteopenia, the promotion of bony ingrowth into prostheses or skeletal defects, and the acceleration of fracture healing. These goals are approached via interdisciplinary studies at the biochemical, molecular, cellular, tissue, organ, computational (e.g., FEM), and clinical levels.
(631) 652-8521, Clinton.Rubin@stonybrook.edu

 

NICOLE S. SAMPSON, Associate Professor
Ph.D. 1990, University of California at Berkeley
Department of Chemistry
Nicole Sampson’s research combines the areas of bio-organic chemistry, biochemistry, and molecular and cellular biology. She is interested in enzyme mechanisms of conformational changes, and has focused on structure-function studies of steroid-binding and barrelenzymes. She has developed experimental probes for testing how cholesterol oxidase interacts with the lipid membrane. These studies are important for investigations of membrane structure with cholesterol oxidase and understanding its insecticidal properties. She is also interested in the role of the ADAM family of cellular ligands in mammalian fertilization. Recently, her laboratory identified the receptor for one ADAM protein, fertilin, which is important for sperm-egg binding as _6_1 integrin. Peptido-mimetics of receptor-ADAM ligand interactions are being synthesized and tested to investigate the roles of other ADAM proteins.
(631) 632-7952, Nicole.Sampson@stonybrook.edu

 

SUZANNE F. SCARLATA, Professor
Ph.D. 1984, University of Illinois
Department of Physiology and Biophysics
Suzanne Scarlata’s laboratory is interested in the role of lipid membranes in regulating the association and oligomerization of membrane proteins. The association of membrane proteins is viewed by several biochemical and biophysical techniques, the most prominent of which is fluorescence spectroscopy. Currently, both traditional and newly developed fluorescence methods are being used to study two different biochemical problems. The first of these is the mechanism through which G protein subunits activate phospholipase C effectors. These studies include the energetics and kinetics associated with these interactions and the role of modular domains in mediating associations and activation. The second problem seeks to understand the specific molecular interactions that drive the assembly of HIV 1 proteins on the membrane surface of host proteins and the role of different cellular factors in assembly. These studies involve fluorescence techniques, as well as light scattering, sedimentation, and molecular footprinting.
(631) 444-3071, suzanne@dualphy.pnb.sunysb.edu

RICHARD B. SETLOW, Senior Biophysicist
Ph.D. 1947, Yale University
Biology Department, Brookhaven National Laboratory
Richard Setlow is a member of the National Academy of Sciences. He is interested in the quantitative effects of ionizing, ultraviolet, and sunlight radiations on molecules and on living creatures. He showed, using back cross hybrid fish of the genus Xiphophorus that have only one tumor suppresser gene for melanoma, that the most important spectral region in sunlight responsible for inducing melanomas was in the longer ultraviolet, the so-called UVA (320-400 nm). These wavelengths are not absorbed by conventional sunscreens.
Setlow is now working on the use of the Japanese fish, Medaka, to investigate the risks of the high-energy, high-atomic-number cosmic rays that would be encountered by astronauts on trips beyond Earth’s orbit, by measuring germ cell mutations in exposed males. Wild type males will be exposed to nuclei from a high-energy accelerator at Brookhaven National Laboratory and mated to females with five homozygous recessive color loci. The developing eggs are observed microscopically for dominant lethals and for color mutations so as to obtain mutation frequencies as a function of dose.
(631) 344-3391, setlow@bnl.gov

 

STEVEN O. SMITH, Professor and Director, Center for Structural Biology
Ph.D. 1985, University of California at Berkeley
Department of Biochemistry and Cell Biology
Steven Smith is the Director of Structural Biology in the Centers for Molecular Medicine. His research involves understanding in structural and chemical terms how membrane proteins function. His work focuses on the molecular mechanisms of signal transduction by G protein-coupled receptors and receptor tyrosine kinases, and the mechanism of selectivity and gating by ion channel proteins. His research on signal transduction mechanisms mediated by protein conformational changes has involved the visual pigment rhodopsin, a seven-transmembrane helix receptor in vertebrate rod cells responsible for vision in dim light, and CCR5, one of the co-receptors for entry of HIV into T-cells. Current projects involving signal transduction mediated by receptor oligomerization focus on two receptor proteins—the neu or erbB-2 receptor and the platelet-derived growth factor (PDGF) receptor—that can be constitutively activated through interactions involving their transmembrane domains. Finally, structure-function studies are in progress on phospholamban, a 52-residue ion channel protein found in cardiac sarcoplasmic reticulum (SR) that regulates calcium levels across the SR membrane.
(631) 632-1210, Steven.O.Smith@stonybrook.edu

 

IRENE C. SOLOMON, Associate Professor
Ph.D. 1994, University of California at Davis
Irene Solomon’s laboratory seeks to understand the mechanisms by which central nervous system (CNS) neurons integrate peripheral and central inputs in respiratory and cardiovascular control. Solomon is investigating CNS sites and neuropharmacological mechanisms mediating hypoxic ventilatory and sympathetic responses. Severe brain hypoxia which may result from numerous cardiovascular and respiratory diseases (e.g., stroke, corpulmonale) results in a shift from respiratory depression excitation (gasping) and an increase in sympathetic output. Solomon’s lab examines the brainstem sites and neural mechanism(s) responsible for this shift in respiratory patterning, as well as the synchronization of the central respiratory cycle with sympathetic activity. The experimental approach in the laboratory involves neuroanatomical mapping, electrophysiological recording, and neuropharmacology. Another focus of research examines reflex and central neural control of the airways.
(631) 444-2932, icsolomon@physiology.pnb.sunysb.edu

 

Ilan Spector, Associate Professor
Ph.D. 1967, University of Paris, France
A general research interest of Ilan Spector’s laboratory is the discovery of new pharmacological agents derived from marine organisms, which represents today the richest untapped reservoir of biologically active agents with unique structural features not encountered in terrestrial natural products. The lab has identified an extensive battery of marine natural products that target the actin cytoskeleton, a major determinant of cell shape, motility, and adhesion, which control important biological processes such as tissue morphogenesis, cell growth and differentiation, wound healing, and malignant transformation. Spector and his team are using these agents to specifically perturb cytoskeletal structures, to modulate the state of actin filament assembly, and to gain insight into the functions, organization, and dynamics of the actin cytoskeleton. The group has also identified new classes of marine compounds that regulate cellular growth and differentiation and are investigating their mechanism of action.
(631) 444-3447, Ilan.Spector@stonybrook.edu

Peter J. Tonge, Associate Professor
Ph.D. 1986, University of Birmingham, U.K.
Department of Chemistry
Peter Tonge’s research focuses on developing precise structure-reactivity correlations for enzyme-catalyzed reactions using spectroscopic techniques, such as vibrational spectroscopy and NMR spectroscopy. Detailed information is obtained concerning the geometry of the bound substrate, the energy of specific enzyme-substrate contacts, and the changes that occur in the electronic structure of the substrate on binding. This approach provides fundamental insight into the mechanism of enzyme catalysis and facilitates the rational design of enzyme inhibitors for use as novel therapeutics. Drug-design efforts are focused on an enzyme from Mycobacterium tuberculosis, which is a target for the antitubercular drug isoniazid. A recent highlight of this work has identified triclosan, an additive in many personal care products such as toothpaste, as an inhibitor of this enzyme. Tonge is also investigating how proteins cause and stabilize charge rearrangement with emphasis on enzymes involved in fatty acid oxidation. Finally, research efforts on green fluorescent protein (GFP) are seeking to determine how the fluorescent properties of the GFP chromophore are modulated by the protein environment.
(631) 632-7907, Peter.Tonge@stonybrook.edu

Hsien-yu Wang, Research Associate Professor
Ph.D. 1989, Stony Brook University
Hsien-yu Wang’s long-term goals are to study transmembrane signaling by
heterotrimeric G-proteins, focusing on their role in mediating Frizzled receptors. The Frizzled 1 gene structure has been solved and the cell-surface receptor for Wnt ligands is heptihelical, suggestive of coupling by members of the heterotrimeric G-protein family. Purification of active Wnt ligands has not been successful and the Wang lab has now succeeded in crafting a new strategy with which to study the signaling of Frizzled receptors, creating chimeric receptors in which the cytoplasmic domains of Rfz1 and Rfz2 are substituted into the beta-adrenergic receptor (b2AR). The b2AR/Rfz2 chimera, for example, signals with Rfz2 character to downstream effectors in Xenopus, zebrafish, and mammalian cells, although now fully activated by an agonist ligand for the b2AR. With this proof-of-concept, a b2AR/Rfz1 chimera has been created as a tool for study of signaling and biology of Rfz1 in F9 teratocarcinoma stem cells in culture. Preliminary data demonstrate that activation of the b2AR/Rfz1 chimera with isoproterenol promotes stabilization of beta-catenin, JNK activation, and primitive endoderm formation in F9 cells and expression of target gene (Siamois and Xnr3) in Xenopus.
(631) 444-7873, wangh@pharm.sunysb.edu

 

Thomas W. White, Associate Professor
Ph.D. 1994, Harvard University
Intercellular channels present in gap junctions allow cells to share small molecules and thus coordinate a wide range of behaviors. In vertebrates, a large family of genes known as connexins encodes these gap junctional channels, and mutations in human connexins underlie a variety of diseases, including deafness, skin diseases (keraotdermas), demylinating neuropathies, and lens cataracts. In addition, gene targeting of connexins in mice has provided new insights into connexin function and revealed a variety of unexpected phenotypes. Thomas White is interested in how different members of the connexin family fulfill unique functions in tissue homeostasis, and use genetically engineered mice to probe the unique communication requirements of different tissues. He also uses electrophysiological assays to determine the alterations in channel function that arise from connexin mutations that cause human hereditary disease.
(631) 444-9683, Thomas.White@stonybrook.edu

 

Stanislaus S. Wong, Assistant Professor
Ph.D. 1999, Harvard University
Stanislaus Wong and his group have wide-ranging interests in the science of nano-technology. The focus of the research is to understand intermolecular interactions at the nanometer scale, critical in understanding problems such as friction and lubrication, binding energies on surfaces essential for the design of effective catalysts, as well as phenomena such as chemical and biological self-assembly. The Wong lab studies fundamental structure-correlations in unique nanostructures (as low as 1 nm in dimension), such as carbon nanotubes and oxide nanocrystals, with an intent on exploiting them for novel applications in physics, chemistry, and biology. Some of Wong’s work has been featured in a cover article in the international scientific journal Nature. Wong holds a joint appointment at Brookhaven National Laboratory.
(631) 632-1703, sswong@ms.cc.sunysb.edu

 

Mark Bowen , Assistant Professor
Ph.D. 1998, University of Illinios , Chicago
Molecular aspects of Signal transduction

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