Molecular and Cellular Biology - The Graduate School at Stony Brook University

Our Distinguished Faculty

On the following pages you will be introduced to faculty in the Molecular and Cellular Biology Graduate Program. Our faculty are actively engaged in research that is recognized internationally and funded by a variety of sources, including the National Institutes of Health, the National Science Foundation, the American Cancer Society, and many state and private sources. They are editors of leading scientific journals, and officers of prominent scientific societies.

benach JORGE BENACH, Professor and Director, Center for Infectious Diseases
Ph.D. 1972, Rutgers University
Department of Molecular Genetics and Microbiology

Jorge Benach’s research focuses on the pathogenesis of spirochetal infections and their host responses, particularly how it is manifested in Lyme disease and Rocky Mountain spotted fever. Benach was a 1992 Fulbright-Hays Fellow and Exchange Professor.
(631) 444-3520, jbenach@path.som.sunysb.edu

lennarz WILLIAM J. LENNARZ, Distinguished Professor and Chairman
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, PDI, the enzyme that catalyzes folding and disulfide bond formation in glycoproteins, is being studied.
(631) 632-8560, wlennarz@notes.cc.stonybrook.edu
Website - http://ws.cc.stonybrook.edu/biochem/lennarz/index.html

BRUCE STILLMAN, President and Professor
Ph.D. 1979, Australian National University
Cold Spring Harbor Laboratory

Bruce Stillman’s research focuses on the processes that ensure accurate inheritance of genetic material from one cell generation to the next. He has contributed to the discovery of many DNA replication proteins that function to replicate the human genome. Stillman studies the mechanism and cell cycle control of initiation of chromosomal DNA replication in the yeast Saccharomyces cerevisiae and human cells. His laboratory elucidated the structure of chromosomal origins of DNA replication and origin binding proteins. One of these, the Origin Recognition Complex (ORC), facilitates initiation of chromosome DNA replication. ORC also functions as a landing pad for other replication proteins, including Cdc6, the MCM helicase, and cyclin CDKs. Stillman has studied the mechanism of inheritance of chromatin and epigenetically determined states of gene transcription. He has shown that this process involves interaction between the chromatin assembly factor CAF-1 and PCNA, a DNA replication protein. A native of Australia, Stillman is a fellow of the Royal Society and a member of the National Academy of Sciences.
(516) 367-8383, stillman@cshl.org

haltiwanger KENNETH R. SHROYER, Professor and Marvin Kuschner Chair
Ph.D., 1983, University of Colorado
M.D., 1987, University of Colorado

Dr. Shroyer is Board Certified in Anatomic and Clinical Pathology (1991), with subspecialty certification in Cytopathology (1995) His laboratory is focused on the molecular characterization of benign, premalignant, and malignant lesions of the female genital tract. His laboratory pioneered methods to evaluate x-chromosome inactivation in archival tissues as a marker of monoclonality and developed and evaluated the expression of a wide range of novel molecular assays of cellular immortalization and malignant transformation, including telomerase, HPV, survivin, p16, and B7-H4. Current studies are concentrated on the analysis of p16 overexpression in cervical cytology specimens, as a surrogate marker of human papillomavirus integration and malignant transformation. His laboratory also provides a resource for investigators that are interested in a wide range of tissue-based studies, including Immunohistochemistry, in situ hybridization, microdissection, and DNA/RNA nucleic acid amplification.
Contact : (631)-444-3000, kenneth.shroyer@stonybrook.edu

frohman MICHAEL A. FROHMAN, Professor, MSTP Director, and Interim Chair
M.D., Ph.D. 1985, University of Pennsylvania
Department of Pharmacological Sciences

Mike Frohman's lab studies lipid signals that alter cell morphology, regulate mitochondrial fusion, and trigger subcellular trafficking of membrane vesicles during regulated exocytosis and endocytosis. Disease-related topics include neurodegenerative disease (Charcot-Marie Tooth syndrome), diabetes, cancer, and impaired phagocytic immune responses to pathogens.The specific topic constitutes study of signaling pathways mediated by members of the superfamiles of enzymes known as Phospholipase D (PLD) and PI4P Kinase. Classic PLD is activated by a wide variety of agonists that signal through G-protein coupled or tyrosine kinase receptors. PLD has varied cellular roles including facilitating membrane vesicle trafficking and fusion of the vesicles into the plasma membrane during regulated exocytosis, and reorganizing the actin cytoskeleton. The lab is currently investigating roles for PLD and PI4P lipid kinase in actin cytoskeleton reorganization, myoblast differentiation and fusion, Glut-4 glucose transporter translocation, phagocytosis, and regulated exocytosis (insulin and histamine release). In addition, lab members are exploring a novel member of the PLD superfamily that localizes to mitochondria and regulates fusion, and the mechanisms through which diminished rates of fusion cause neurodegenerative disease.
(631) 632 -1476 , michael@pharm.sunysb.edu,
http://www.pharm.stonybrook.edu/faculty/frohman/lab/

ROBERT S. HALTIWANGER, Professor and Interim Chair
Ph.D. 1986, Duke University
Department of Biochemistry and Cell Biology

The goal of the work in Robert Haltiwanger’s laboratory is to investigate the role of protein glycosylation in development and signal transduction pathways. In particular, they are studying the structure and function of two unique forms of protein O-glycosylation that occur on Epidermal Growth Factor-like (EGF) modules, termed O-linked fucose and O-linked glucose. Haltiwanger has recently demonstrated that the Notch protein bears these forms of glycosylation. Notch is a cell surface signaling receptor that contains multiple EGF modules and plays a key role in a wide variety of developmental cascades. The Haltiwanger lab has also shown that the Fringe protein, a known modifier of Notch function, is a glycosyltransferase that adds an N-acetylglucosamine to the 3'-OH of O-linked fucose on Notch. Thus, the O-linked fucose modifications play a key role in modulation of the Notch signaling pathway. This is the first demonstration that signal transduction events can be regulated at the level of differential receptor glycosylation, providing a new paradigm for the role of glycosylation in signaling events.
Contact - (631) 632-7336, rhaltiwanger@ms.cc.sunysb.edu
Website - http://www.sunysb.edu/biochem/haltiwanger/index.html

FACULTY (A-Z):

neiman AARON NEIMAN, Associate Professor
Ph.D. 1994, University of California at San Francisco
Department of Biochemistry and Cell Biology

Research in the Neiman lab is focused on understanding the molecular mechanisms underlying sporulation in the baker's yeast Saccharomyces cerevisiae. Formation of spores proceeds in two phases; first, an unusual cell division in which the daughter cell plasma membranes are formed de novo followed by the assembly of a complex extracellular matrix, the spore wall. Both of these events are under study in the laboratory. A combination of genetic, cell biological, and biochemical approaches are used to identify genes required for these processes and elucidate the function of the proteins encoded by these genes.
(631) 632-1543, Aaron.Neiman@sunysb.edu ,
http://www.stonybrook.edu/biochem/neiman/index.html

krainer ADRIAN R. KRAINER, Professor
Ph.D. 1986, Harvard University
Cold Spring Harbor Laboratory

Adrian Krainer’s research focuses on the mechanisms and regulation of messenger RNA splicing in human cells. Biochemical and molecular approaches are used to identify and characterize protein components of the spliceosome and to understand how these components participate in splicing catalysis, splicing fidelity, and the regulation of gene expression by alternative splicing. Structure and function analysis of splicing components, such as RNA-binding proteins of the SR and hnRNP A/B protein families and the protein erine/threonine phosphatase PP2Cgamma, are used to dissect the mechanisms of spliceosome assembly and splice-site selection. His laboratory is also studying the mechanisms by which single point mutations in exons result in exon skipping, thereby causing a variety of genetic diseases. For example, a single-nucleotide difference between the SMN1 and SMN2 survival-of-motor neuron genes, which are involved in the neurodegenerative disease spinal muscular atrophy, and a nonsense mutation in the BRCA1 breast-cancer susceptibility gene cause inappropriate exon skipping.
(516) 367-8417, krainer@cshl.org

wimmer ALEA A. MILLS, Associate Professor
Ph.D 1997, University of California Irvine
Cold Spring Harbor Laborator

Alea Mills is interested in defining the genetic basis of tumorigenesis, as well as in understanding how cancer genes impact development, stem cells, and aging. In order to identify novel genes that modulate the tumorigenic process in an in vivo setting, the Mills group generates and characterizes novel mouse models. Using a combination of gene targeted disruption, conditional inactivation, and gene-targeted knock-in, the Mills lab has uncovered an unexpected role for the p53 homolog p63 in development, senescence, cancer, and aging. Using chromosome engineering, a genomic strategy that combines the power gene targeting and Cre/loxp technology, the Mills group recently identified a region of the mouse genome corresponding to a region frequently deleted in a wide variety of human cancers. Genetic screens using these models allowed them to identify the chromatin remodeling-encoding gene, Chd5, as a novel tumor suppressor that serves as a master switch for a tumor suppressive network. Current work is aimed at understanding how p63 and Chd5 affect stem cell renewal, aging, and cancer.
Contact - (516) 367-6910 ,mills@cshl.edu
Website - http://gradschool.cshl.edu/mills_.html
http://www.cshl.edu/cancercenter/current_initiatives.html

ARNE STENLUND, Associate Professor
Ph.D. 1984, Uppsala University, Sweden
Cold Spring Harbor Laboratory

Arne Stenlund studies the DNA replication properties of papillomaviruses, a very large family of viruses that infect and transform the basal epithelium in their hosts and induce proliferation of cells at the site of infection. Certain types of papillomaviruses give rise to tumors that are prone to progress toward malignancy, frequently causing cervical cancer. Stenlund’s lab has two primary goals: to acquire a detailed understanding of the processes required for DNA replication from the papillomavirus origin of replication, a requirement for understanding the viral life cycle; and to use the papillomavirus replication system to gain a general understanding of DNA replication at the biochemical level. Stenlund is particularly interested in three universally required, fundamental processes for the initiation of DNA replication: site-specific recognition of the origin of replication; local strand separation or distortion; and loading of a replication helicase.
(516) 367-8455, stenlund@cshl.org

ARTHUR P. GROLLMAN, Distinguished Professor
M.D. 1959, Johns Hopkins University
Department of Pharmacological Sciences

Research in the Laboratory of Chemical Biology (LCB), for which Dr Grollman serves as Director, focuses on the biological consequences of DNA damage with specific reference to molecular mechanisms of DNA replication, mutagenesis, and DNA repair. Research in the LCB was instrumental in establishing the mechanism of action of bleomycin and in defining an important error-avoidance pathway that protects cells against mutations resulting from miscoding effects of oxidative DNA damage. He and his collaborators established the three-dimensional structures of DNA glycosylases and DNA polymerases bound to site-specifically modified DNA, thereby correlating the molecular structure of damaged DNA with enzymatic function. Current research focuses on molecular and cellular mechanisms involved in the nephrotoxicity of the human carcinogen, aristolochic acid.
Contact - (631) 444-3080, apg@pharm.sunysb.edu
Website - http://www.lcb.stonybrook.edu/

BERNADETTE C. HOLDENER, Associate Professor
Ph.D. 1990, University of Illinois at Chicago
Department of Biochemistry and Cell Biology

Bernadette Holdener’s research uses the mouse to understand the genetic regulation of mammalian development. She is interested in many aspects of development, ranging from the earliest tissue differentiation to complex tissue interactions required for organ development. Characterization of existing mouse mutations and the generation of new mutations are central to her studies. Laboratory studies focus on mutations that disrupt early embryonic patterning, mesoderm induction, neural differentiation, and the development of cardiac-neural-crest-derived tissues.
(631) 632-8292, holdener@life.bio.sunysb.edu

simerling CARLOS SIMMERLING, Assistant Professor
Ph.D. 1994, University of Illinois at Chicago
Department of Chemistry

Carlos Simmerling is a chemist whose interests lie in the structure and motion of biomolecules such as proteins and nucleic acids. Experimental approaches often fail to reveal accurate three-dimensional protein structures, and the process by which the protein attains this conformation. His work therefore focuses on the development of novel computer simulation approaches intended to supplement experimental data. Simmerling is an active member of the development team for the widely used AMBER suite of molecular simulation programs and is sole developer of a freely available molecular graphics program. He is particularly interested in the application of his simulation tools to the refinement of low-quality experimental structures in order to provide “chemical” accuracy that can be used to determine and modify function. Recent efforts have focused on the high-throughput refinement tools that will become increasingly important as genome sequence data becomes available.
Contact - (631) 632-1336, Carlos.Simmerling@stonybrook.edu
Simmerling Lab : http://comp.chem.sunysb.edu

malbon CRAIG C. MALBON, Leading Professor
Ph.D. 1976, Case Western Reserve University
Department of Pharmacological Sciences

Cellular signaling from receptors in the cell membrane to intracellular compartments, especially the nucleus, is a nexus supporting early development, regulation of metabolic function, and when dysregulated, human diesases such as cancer, obesity, and diabetes. We probe two primary signaling pathways, the Wnt-Frizzled pathways controling development and the adrenergic pathways controlling metabolic regulation. The advent of siRNA-catalyzed knock-down, conditional overexpression, biosensors for protein-protein-interactions, and BRET/FRET enable us to probe the temporal and spatial aspects of cell signaling, focusing upon the key role of molecular scaffolds. Study of AKAP scaffolds (such as gravin of AKAP79) and of dishevelled reveals new and unexpected roles for these scaffolds that catalyze efficient, rapid signaling with high-spatial restriction within the cell. We investigate the structural basis for the dynamic docking of protein kinases, phosphatases, and adaptor molecules that enable proper cell signaling, making use of a full armamentarium of high-tech probes to garner new insights.
(631) 444-7873, craig@pharm.sunysb.edu,
http://www.pharm.stonybrook.edu/Faculty/Professors/
Craig_C._Malbon%2C_PhD_-_Leading_Professor/

deutsch DALE DEUTSCH, Professor
Ph.D. 1972, Purdue University
Department of Biochemistry and Cell Biology

Metabolism of the Endocannabinoids, Anandamide and 2-AG - Anandamide and 2-AG are endogenous compound that binds to the cannabinoid receptor as does THC, the active component of marijuana. Anandamide and 2-AG are very important neurotransmitter since they affects mood, memory, pain, appetite, response to stress, and many other physiological processes. My laboratory described the enzyme in the brain that hydrolyzes anandamide in 1993. It is now called FAAH, an abbreviation for the fatty acid amide hydrolase. Over the years we have undertaken basic research to understand how FAAH works to regulate anandamide levels. With the long-term goal of developing drugs to regulate the endocannabinoids, we are studying the mechanism by which anandamide is inactivated. This involves a two-step process with anandamide first being taken-up by the cells and subsequently being hydrolyzed by FAAH. We are also studying the localization of FAAH at the cellular level and are also interested in the synthesis of anandamide and are now characterizing a conditional NAPE-PLD KO animal. Most recently we have become interested the mechanism by which 2-AG is transported into the cell (simple diffusion, via an endocannabinoid transporter, or endocytosis).
Contact - (631) 632-8595, DDeutsch@notes.sunysb.edu
Website - http://www.sunysb.edu/biochem/deutsch/index.html

DANIEL BOGENHAGEN, Professor
M.D. 1977, Stanford University
Department of Pharmacological Sciences

Mitochondria play a vital role in cell survival by generating ATP through carbohydrate, lipid and amino acid metabolism. They also produce heme, iron sulfur clusters, and reactive oxygen species and regulate apoptosis. The maintenance of mitochondria depends on expression of the mtDNA genome to provide a small number of gene products that are assembled into respiratory complexes along with other subunits encoded in nuclear genes whose products are imported into mitochondria. Thus, mitochondria provide an ideal opportunity to study the coordinate regulation of cell function at all genetic levels, from replication and repair to transcription and translation. We have developed the MiGenes web site http://www.pharm.stonybrook.edu/migenes/ to catalog and characterize the hundreds of proteins that function in mitochondria. Over 130 of these proteins are implicated in specific human diseases. The Bogenhagen laboratory is engaged in studies of many of the key proteins involved in maintenance of mtDNA, including the heterotrimeric DNA polymerase, RNA polymerase, two transcription factors, mtDNA ligase, DNA helicase, mitochondrial single-stranded DNA binding protein and other components of the mitochondrial nucleoprotein complex.
(631) 444-3068, Dan@pharm.sunysb.edu

DAVID G. THANASSI, Associate Professor
Ph.D. 1995, University of California at Berkeley
Department of Molecular Genetics and Microbiology

Pathogenic bacteria must express virulence factors to interact with host tissues and cause disease. Our lab is interested in understanding virulence protein secretion by Gram-negative bacteria and the roles of virulence factors in causing disease. One focus of our research is pilus biogenesis by uropathogenic Escherichia coli , the predominant causative agent of urinary tract infections. Pili are essential virulence organelles that radiate out from the bacterial cell surface, mediating recognition of and binding to host cells. In particular, we are interested in understanding the structure and function of an essential pilus assembly protein termed the usher. A second focus of our research is identifying and characterizing virulence factors of Yersinia pestis and Francisella tularensis . Y. pestis and F. tularensis are the causative agents of plague and tularemia, respectively. Both of these bacteria are extremely virulent for humans when aerosolized and are classified as Category A agents of bioterrorism. Genome sequence analysis of Y. pestis revealed the presence of numerous gene clusters related to the E. coli pili described above. We are investigating the function of these genes and their roles in Y. pestis pathogenesis. The molecular basis for the virulence of F. tularensis is largely unknown. We are identifying and characterizing potential virulence factors of F. tularensis , focusing on surface and secreted proteins. The identification of virulence factors combined with a detailed understanding of virulence factor biogenesis will elucidate mechanisms of pathogenesis and provide targets for the design of novel therapeutic reagents.
(631) 632-4549, David.Thanassi@Stonybrook.edu,
http://www.mgm.stonybrook.edu/thanassi/index.shtml

spector DAVID L. SPECTOR, Professor
Ph.D. 1980, Rutgers University
Cold Spring Harbor Laboratory

David Spector seeks to understand the spatial organization of gene expression. While much information is available from in vitro studies as to the factors that are involved in gene expression, and in particular RNA processing, much less is known about how these factors find their substrates in the living cell. The Spector laboratory has taken a molecular/cell biological approach to elucidate the intranuclear dynamics and signals involved in the movement of RNA processing factors from assembly/modification sites to sites of active transcription. To complement their cell biological studies, they have taken a biochemical approach and purified and biochemically characterized a nuclear structure, interchromatin granule clusters, that is enriched in pre-mRNA processing/transcription factors. This interdisciplinary approach will establish the in vivo parameters necessary for efficient gene expression and will serve as the basis from which to study alterations in nuclear function related to various diseases.
(516) 367-8456, spector@cshl.org , http://spectorlab.cshl.edu/

brown DEBORAH A. BROWN, Professor
Ph.D. 1987, Stanford University
Department of Biochemistry and Cell Biology

Recent work has shown that lipids in biological membranes do not always mix uniformly. Instead, membranes contain microdomains that are enriched in certain lipids. Deborah Brown studies cholesterol- and sphingolipid-rich membrane domains called rafts. Rafts play important roles in cell-surface signal transduction, cell polarity, and protein sorting in the secretory and endocytic pathways. These functions result from the fact that certain proteins have a high affinity for the unique lipid environment found in rafts and are concentrated in the domains. Brown combines cell biological and biophysical approaches to study how lipids and proteins associate in rafts, how rafts are organized in cell membranes, and how they function. Some rafts are found in plasma membrane pits called caveolae. Caveolae are formed from homo-oligomers of an unusual membrane protein called caveolin, which has been implicated in integrin signaling and regulation of cell growth. Brown uses caveolin mutants to learn how caveolin interacts with rafts and how this interaction is important in the function of caveolae.
(631) 632-8563, Deborah.Brown@stonybrook.edu

wimmer ECKARD WIMMER, Distinguished Professor
Ph.D. 1962, University of Göttingen, Germany
Department of Molecular Genetics and Microbiology

Eckard Wimmer’s group studies human pathogenic viruses whose genomes are single-stranded RNA and serve, after invasion into the host cell, as messenger RNA (plus strand RNA viruses). These include enteroviruses, particularly poliovirus and coxsackie viruses, and hepatitis C virus (HCV), a flavivirus. With respect to virion structure, replication and pathogenesis, enteroviruses and HCV could not be more different. Poliovirus is non-enveloped with a short (7 hr) lytic infectious cycle that only rarely (2 percent of infections) causes a neurologic disease (poliomyelitis). It can be produced in large quantities and can be studied in transgenic mice. HCV, an enveloped virus that is very difficult be propagated in tissue culture cells or experimental animals to reasonable quantities, causes chronic liver disease (70 percent of infections). And yet the general gene organization of these viruses is remarkably similar. It is the objective of Wimmer’s research group to decipher the molecular basis of replication and pathogenesis of enteroviruses and HCV (cellular receptors, parameters of tissue tropism, control of gene expression, genome replication).
(631) 632 8787, ewimmer@ms.cc.sunysb.edu

BOON ELIZABETH BOON, Assistant Professor
Ph.D. 2002, California Institute of Technology
Department of Chemistry, Stonybrook University

Prokaryotic Nitric Oxide Biology Nitric oxide (NO) has diverse and important roles in eukaryotic biology. In addition to its role as a powerful toxin used to kill invading pathogens and tumor cells, NO functions as a signaling molecule that mediates many functions such as smooth muscle relaxation, neuronal signal transduction and inhibition of platelet aggregation. In eukaryotes, the heme group of the enzyme soluble guanylate cyclase (sGC) is the specific receptor of the NO signal. Genomic analysis has recently placed sGC within a larger family of heme proteins including prokaryotic proteins with significant homology (15-40% identity) to the heme domain of sGC, called the H-NOX family, for Heme Nitric oxide and/or OXygen binding domain. What is the function of the H-NOX family in bacteria? Are they NO sensors? The discovery of the H-NOX family has lead to several lines of research in our group.
Contact - (631) 632-7945, elizabeth.boon@sunysb.edu
Boon Group - http://ms.cc.sunysb.edu/~eboon/home.html

mackow ERICH R. MACKOW, Associate Professor
Ph.D. 1984, Temple University
Department of Medicine

Erich Mackow’s interests are in the molecular mechanisms of rotavirus and hantavirus pathogenesis. Rotavirus activation of NF-kB and regulation of JNK activation is being investigated to define the mechanism by which rotaviruses direct pathway specific cellular responses which permit their successful replication in enterocytes. The means by which the rotavirus NSP5 protein regulates protein insolubility, hyperphosphorylation and dephosphorylation to direct viroplasm formation is being addressed. Hantavirus studies include; 1) Investigating the use of inactive avb3 integrins by only pathogenic hantaviruses and the role of avb3 integrin regulation on enhanced permeability of the endothelium; 2) Investigation of pathway specific regulation of IFN responses by a proteins from pathogenic hantaviruses; 3) Investigation of the role of viral protein ubiquitination and degradation on hantavirus regulation of cell signaling responses; and 4) Developing a hantavirus reverse genetics system to modify hantaviruses and define virulence determinants.
(631) 444-2120, erich.mackow@stonybrook.edu

london ERWIN LONDON, Professor
Ph.D. 1980, Cornell University
Department of Biochemistry and Cell Biology

Erwin London’s interests involve membrane structure and function. In one project Dr. London's lab 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. The labs second project involves exploring the function of lipid domains enriched in cholesterol and sphingolipid (lipid rafts). 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 (in collaboration with the lab of Deborah Brown) is to determine the principles that induce formation of these domains and regulate their lipid and protein composition. A third project involves understanding how proteins translocate across membranes using diphtheria toxin. The structure of this toxin within membranes, and its translocation across membranes, 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.
Contact - (631) 632-8564, Erwin.London@stonybrook.edu

GARY ZIEVE GARY ZIEVE, Associate Professor

Gary Zieve’s laboratory studies RNA-protein interactions and autoimmunity. We using the Sm proteins that form heteroheptameric rings that bind RNA as our model system. In eukaryotes these protein help build the snRNP particles that bind snRNAs and function in pre-mRNA splicing. These proteins are also major autoantigens in Lupus. Bioinformatic approaches have identified conserved protein motifs that form nucleotide binding pockets. Compensatory changes in RNA and proteins have illuminated critical features of the interactions. Biochemical studies are investigating the assembly pathways of the RNA-protein complexes. Autoimmunity against the Sm proteins is the result of T cell epitopes embedded in the Sm protein fold and B cell motifs that center on highly methylated domains in the protein tails. The laboratory is investigating strategies to interfere with the autoimmune recognition of the proteins.
(631) 444 3140, gary.zieve@stonybrook.edu
Website - http://www.path.sunysb.edu/gz/

thomsen GERALD H. THOMSEN, Associate Professor
Ph.D. 1988, The Rockefeller University
Department of Biochemistry and Cell Biology

Gerald Thomsen studies vertebrate embryonic development and its fundamental importance to general biological knowledge and to medicine. As the various model organism genome projects progress, embryology is poised to play an increasingly important role in illuminating the function of newly discovered genes. Thomsen’s research focuses on the transforming growth factor-B (TGFB) in developing vertebrate embryos of the frog, Xenopus laevis. The Thomsen lab is interested in how members of the TGFB family, such as Vg1, activin, and bone morphogenetic proteins (BMPs) function to control differentiation and growth of tissues, particularly tissues that form blood, muscle, the heart, head, and nervous system. Thomsen has characterized the biochemical mechanisms of how various TGFBs trigger their effects in cells, discovering that BMPs directly trigger blood differentiation. His lab also studies the role that TGFBs play in the control of human cell growth and cancer.
(631) 632-8536, gthomsen@notes.cc.stonybrook.edu

GREGORY J. HANNON, Professor
Ph.D. 1991, Case Western Reserve University
Cold Spring Harbor Laboratory

Greg Hannon’s laboratory focuses on two major areas: 1) The proliferation of normal cells is tightly regulated by a variety of signaling mechanisms which are generally disrupted in tumor cells. He has focused on identifying genetic alterations that contribute to this loss of control. Using a set of specially designed retroviral vectors that permit phenotypic selection in cultured cells, his lab is presently investigating the minimum genetic requirement for transformation of human cells and the mechanistic basis of genomic instability in human cancer; 2) In a variety of organisms, introduction of dsRNA causes degradation of mRNAs homologous to the dsRNA. This process may represent a cellular defense against exogenous agents and/or a novel gene regulatory mechanism. He has developed an in vitro system that recapitulates RNA interference and has demonstrated that the process is accomplished by a sequence-specific nuclease activity that uses sequences from the input dsRNA to guide RNA degradation. Hannon’s laboratory is presently identifying the responsible proteins and is searching for endogenous targets of this process.
(516) 367-8889, hannon@cshl.org

fleit HOWARD B. FLEIT, Associate Professor
Ph.D. 1980, New York University
Department of Pathology

Howard Fleit is an immunologist whose research focuses on cellular components of the innate immune system. Phagocytic cells, such as macrophages and neutrophils, are members of the innate immune system and have receptors (Fc receptors) on their plasma membranes that bind antibody molecules and thereby bridge the adaptive immune response to cells of the innate immune system. Fleit utilizes biochemical and cell biological techniques to study how different classes of these receptors transduce a signal in the phagocytes to trigger them to release toxic oxygen intermediates, such as superoxide, which can destroy antibody-coated bacteria.
(631) 444-3020, Howard.Fleit@stonybrook.edu

CARRICO HOWARD SIROTKIN, Assistant Professor
PhD, Albert Einstein College of Medicine;

In the long studied but poorly understood process of embryonic development, a single cell will divide and differentiate to form the multitude of cell types found in a mature organism. The research in Dr. Sirotkin's laboratory is directed toward elucidating the signaling interactions that induce and pattern the germ layers in the vertebrate embryo. Of particular interest are the events that govern the development of the neural tube and ultimately produce the diversity of cell types present in the vertebrate nervous system. The laboratory utilizes the zebrafish as a model organism. Several attributes make the zebrafish an ideal system for this analysis: embryos are transparent which allows for observations of cells in vivo, development occurs external to the mother which facilitates cellular manipulations (transplants and gain/loss of function assays) and most importantly, it is a powerful genetic system. Experiments are ongoing to identify and analyze mutations that produce defects in the anterior neural tube and/or specific neural subtypes. Because all vertebrates share fundamental similarities in the organization of their body plans, understanding the genetic networks that control zebrafish development will provide important insights into development of other species including humans.
Contact - Phone: (631) 632-4818, HSirotkin@notes.cc.sunysb.edu
Life Sciences Building, Office 578/Lab 505

nostrand Hsien-yu Wang, Associate Professor of Research
Ph.D. 1990, State University of New York at Stony Brook
Department of Physiology and Biophysics

Wang's lab uses mouse and human embryonic stem cells to study Wnt/Frizzled signaling in development. This includes protein-protein interaction, spacial localization of signaling molecules, signaling pathways and regulation of target gene transcription. Currently the lab is using BRET/FRET, proteomics and other biochemical tools to elucidated the temporal and spacial dynamics of signal transduction in these Wnt-stimulated pathways.
(631) 444-3489, wangh@pharm.stonybrook.edu , http://www.pnb.sunysb.edu/faculty/wang/wang.htm

CARRICO ISSAC CARRICO, Assistant Professor
Ph.D. 2003, California Institute of Technology;
Department of Chemistry

Isaac Carrico utilizes chemical tools to study fundamental physiological processes and develop novel therapeutics. Primarily, his work involves the incorporation of non-native functionality either as unnatural amino acids or sugars. Introduction of non-native functionality facilitates the tracking of physiological processes (i.e. glycosylation events).
Additionally, the lab is exploring the introduction of unique reactivity to re-engineer protein pharmaceuticals and therapeutic viruses.
(631) 632-7935, isaac.carrico@sunysb.edu , http://ms.cc.sunysb.edu/%7Eicarrico/Home.html

gergen J. PETER GERGEN, Professor
Ph.D. 1982, Brandeis University
Department of Biochemistry and Cell Biology

Peter Gergen’s research investigates the regulation of gene expression during embryonic development. A major focus of this research over the last several years has involved studies of the function of the Drosophila Runt protein, the founding member of the Runt domain family of transcriptional regulators. Members of this protein family have pivotal roles in pathways extending from pattern formation and sex determination in insects to the development of bone and blood in humans. The work in the Gergen laboratory takes advantage of the wealth of information on the genetics and cell biology of the early Drosophila embryo to investigate mechanisms of transcriptional activation and repression by Runt domain proteins. This work utilizes several approaches, including forward and reverse genetic studies on gene function in vivo, biochemical structure-function analysis of protein:protein and protein:DNA interactions, and biophysical studies aimed at determining the structure of this novel family of DNA-binding proteins. The integration of these interdisciplinary approaches should provide fundamental new insights into the mechanisms used to regulate gene transcription during animal development.
(631) 632-9030, pgergen@life.bio.sunysb.edu, http://www.sunysb.edu/biochem/gergen/index.html

konopka JAMES B. KONOPKA, Professor
Ph.D. 1985, University of California, Los Angeles
Department of Molecular Genetics and Microbiology

James Konopka’s lab studies signal transduction pathways that regulate cell growth and development. The experimental systems under study include mating pheromone signaling of the budding yeast, Saccharomyces cerevisiae, and the switch to hyphal formation that occurs during infection by the pathogenic yeast, Candida albicans. The mating pheromone receptors are under investigation as a model system for the large family of G protein-coupled receptors that includes many mammalian receptors. The advantage of pursuing receptor studies with S. cerevisiae is that sophisticated genetic approaches can be applied. For example, identification of constitutively active and dominant-negative receptor mutants has revealed important insights into receptor activation. The Konopka lab is also investigating the signal pathways that cause the opportunistic pathogen C. albicans to form elongated hyphae that facilitate infection of a host. Interestingly, there is a high degree of similarity between the hyphal and the pheromone signal pathways. Therefore, the analysis of signal transduction in S. cerevisiae is being used to help determine the molecular mechanisms underlying C. albicans pathogenesis.
(631) 632-8715, James.Konopka@stonybrook.edu

JANET LEATHERWOOD, Associate Professor
Ph.D. 1993, Johns Hopkins University
Department of Molecular Genetics and Microbiology

Janet Leatherwood studies how cyclin-dependent kinases (Cdks) signal a cell to copy its genome and divide. Cdks are master regulators of the eukaryotic cell cycle and control many different events including DNA replication, cell shape changes, transcription programs, mitotic spindle formation, and chromosome condensation. The main goal of the lab is to understand Cdk regulation of DNA replication in a simple eukaryote, the fission yeast Schizosaccharomyces pombe. The fission yeast cell cycle is driven by a single cyclin- dependent kinase known as Cdc2. One of the most important things Cdc2 does is to coordinate DNA replication with growth and division. To achieve this, Cdc2 has two seemingly opposite activities—Cdc2 acts positively to trigger DNA replication, then it acts negatively to prevent re-initiation of DNA replication. Leatherwood and others have identified direct links between Cdc2 and DNA replication initiation complexes. Her lab is using yeast genetics and biochemistry to learn how these links may direct Cdc2 to control DNA replication.
(631) 632-9644, jleatherwood@ms.cc.sunysb.edu

JEFFREY PESSIN, Professor and Chair
Ph.D. 1980, University of Illinois
Department of Pharmacological Sciences

The Pessin laboratory is focused on determining the molecular basis of insulin signaling leading to the regulation of glucose homeostasis. These studies used a variety of cell and molecular biological
approaches, transgenic and knockout mice. Current emphasis is on the pathways controlling intracellular vesicle trafficking of the insulin responsive glucose transporter protein GLUT4 and the coupling between Src family and insulin receptor kinase signals.
(631)-444-3083 , Jeffrey.Pessin@stonybrook.edu

hsieh JEN-CHIH HSIEH, Assistant Professor
Ph.D. 1994, Duke University
Department of Biochemistry and Cell Biology

Jen-Chih Hsieh is interested in the molecular mechanism of an evolutionarily conserved signaling pathway, the Wnt signaling pathway. Wnt signaling plays key roles in the integral development of an organism. When uncontrolled, this pathway also causes several human cancers. The major research focus aims to understand the molecular mechanisms by which Wnt signals are transduced in a regulated manner. This work involves determination of the structures and functions of the receptors for Wnt proteins, biochemical and structural characterization of Wnt proteins, and examination of interactions between Wnt proteins, the receptors and downstream components. A related project aims to understand how disruption of Wnt signaling leads to cancers. This work involves identification of factors governing the specificity of interaction between Wnt proteins and their receptors, identification of genes activated by Wnt signaling, and screening for molecular agents capable of modulating Wnt signaling.
(631) 632-1663, jhsieh@ms.cc.sunysb.edu

prives JOAV PRIVES, Associate Professor
Ph.D. 1968, McGill University, Canada
Department of Pharmacological Sciences

The functioning of synapses—specialized sites of communication between excitable cells—depends on precisely regulated mechanisms of synthesis, assembly, and trafficking of synaptic protein complexes, such as neurotransmitter receptors. Joav Prives studies the vertebrate neuromuscular junction as a model synapse to elucidate the molecular mechanisms by which the assembly and cell surface distribution of nicotinic acetylcholine receptors (AChRs) are regulated. One project is aimed at characterizing the mechanisms by which AChRs are assembled intracellularly, and a complementary study is designed to learn how assembled receptors are directed by neuronal cues into specific subsynaptic membrane regions. The study of AChR biogenesis is aimed at identifying the molecular machinery in the endoplasmic reticulum that directs the precise folding and assembly of the subunits into functional receptors expressed on the cell surface. The second focus is on the mechanisms by which signaling factors from motor neurons direct muscle AChRs to cluster at synaptic sites. The emphasis is on defining the signal transduction pathways controlling receptor localization at synapses.
(631) 444-3139, Joav.Prives@stonybrook.edu

levine JOEL M. LEVINE, Professor
Ph.D. 1980, Washington University
Department of Neurobiology and Behavior

Joel Levine’s major research interest is the glial cells of the nervous system and their interactions with growing and regenerating neurons. After disastrous injury, damaged CNS neurons do not regenerate their axons and the functions these neurons carry out are lost to the organism. This failure to regenerate is due to specific features of the environment of the injured brain. Among these features are high levels of a glial chondroitin sulfate proteoglycan called NG2, which inhibits axon growth from developing neurons and causes the growth cones of these neurons to collapse. His lab uses a combination of biochemical, cell biological, and molecular biological approaches to understand how NG2 inhibits axon growth. Current projects are aimed at mapping different functional domains of NG2 and identifying a neuronal receptor for the NG2. Genetic approaches are being used to determine NG2’s functions in organisms ranging from mice
to Drosophila.
(631) 632-8642, Joel.Levine@stonybrook.edu

dunn JOHN J. DUNN, Senior Microbiologist
Ph.D. 1970, Rutgers University
Brookhaven National Laboratory

John Dunn’s research is to determine the molecular roles that T7 RNA polymerase has in initiation. A primary objective is site-specific “rolling circle” replication of T7 DNA and in T7 packaging. His aim is to identify all the viral and cellular components in the replication and processing complexes and to provide a detailed molecular description of their interactions. Part of his efforts involve using recombinant DNA techniques to exploit the obvious potential of T7’s genetic elements to elicit high level expression of foreign proteins in Escherichia coli. The Dunn lab is using the T7 system to overexpress the genes encoding the major outer membrane proteins of the Lyme disease spirochete Borrelia burgdorferi, which causes a multisystematic disorder that is endemic to Long Island. Overexpression of these gene products may be useful for diagnostic immunoassays and/or production of vaccines against Lyme disease.
(631) 344-3012, jdunn@bnl.gov

JOHN REINITZ, Professor
Ph.D. 1988, Yale University

John Reinitz is a biologist who previously worked in departments of Biological Sciences, Molecular Biology and Biochemistry before coming to the Stony Brook Department of Applied Mathematics and Statistics. The Reinitz lab is dedicated to solving fundamental problems in molecular genetics by the tightly integrated application of the methods of experimental biology, large scale computation, and mathematics. The lab works on two problems: developmental pattern formation and transcription. With respect to pattern formation, the lab are trying to understand how animals form the blueprint for their body pattern, using the blastoderm of the fruit fly Drosophila melanogaster as a model system. This is done by formulating a model of gene regulation in the embryo, expressed as a system of nonlinear ordinary or partial differential equations. These equations are fit to gene expression data by large scale optimization methods. We are also trying to understand the molecular mechanisms of metazoan transcription, with special emphasis on understanding how collections of binding sites give rise to modular enhancers. This problem is addressed by feedforward models fit to experimental data from P-transformed Drosophila embryos.
Contact - (631) 632-8352, reinitz@ams.sunysb.edu
Website - http://flyex.bio.sunysb.edu

marcu KENNETH B. MARCU, Professor
Ph.D. 1975, Stony Brook University
Department of Biochemistry and Cell Biology

The research interests of Dr.Marcu research groups at SUNY Stony Brook and S. Orsola Univ. Hospital of the University of Bologna ( Italy ) include: (1) The regulation and mechanisms of action of the inhibitor of NF- k B kinase (IKK) complex, which is essential for the activation of the NF- k B transcription factor family (pivotal regulators of stress-like responses, innate and adaptive immunity and the survival and growth of normal and malignant cells). Here we are employing different biological systems in a variety of in vitro and in vivo studies to: (a) elucidate novel mechanism(s) of action of IKKalpha and how they overlap or differ with those of its NF-kappaB activating partner kinase IKKbeta in different physiological settings (including innate immune responses in disease states and conversion of normal cells to neoplastic ones) , and (b) to define how NF- k B contributes to a cell's gene expression programming in normal and disease states on a genomic scale. (2) The molecular basis of immunoglobulin heavy chain (Igh) class switch recombination (CSR) in adaptive immune responses. Here our research interests are now focused on a proteomics approach to to define the mechanisms of action of the 'Activated Induced Deaminase' (AID) protein in CSR.
(631) 632-8553, kenneth.marcu@stonybrook.edu , http://crba.it/ ,
http://www.sunysb.edu/biochem/marcu/index.html

karzai Leemor Joshua-Tor, Professor
Ph.D. 1991, The Weizmann Institute of Science, Israel
Cold Spring Harbor Laboratory

Professor Joshua-Tor reasearch involves the study of the molecular basis of cell regulatory processes by using the tools of structural biology and biochemistry to examine proteins and protein complexes associated with these processes. Her efforts largely center on nucleic acid regulatory processes.The introduction of double-stranded RNA into a cell can trigger a gene silencing process called RNA interference (RNAi). Although there has been remarkable progress in unraveling the components of the RNAi machinery, we are just beginning to understand how they work at the molecular level. Therefore, the Joshua-Tor lab embarked on structural and biochemical studies of these proteins. By solving the structure of a full-length Argonaute protein, a key component in the RNAi machinery, they identified Argonaute as “Slicer”, the enzyme that cleaves the mRNA as directed by the siRNA. These studies enhance our understanding of this pathway, and should also improve the use of RNAi as a tool for gene knockdown technology. Another system is DNA replication initiation in papillomaviruses. Papillomaviruses are DNA tumor viruses that cause benign and malignant lesions in humans. To gain insight into the mechanism of replication initiation, they are studying two viral proteins that are required for viral replication, the initiator E1 and the transcription factor E2, and their complexes. Based on crystal structures of the E1 hexameric helicase in complex with nucleotide and ssDNA as well as structures of DNA complexes of the DNA-binding domain, they presented a strand exclusion mechanism by sequential ATP hydrolysis for helicase activity of the initiator. This mechanism has wide implications for many oligomeric ATPases.
Contact : (516)367-8821, leemor@cshl.edu
Website : http://joshua-torlab.cshl.edu/

aelst LINDA VAN AELST, Associate Professor
Ph.D. 1991, Catholic University of Leuven, Belgium
Cold Spring Harbor Laboratory

Research in Linda Van Aelst’s lab centers on signal transduction pathways that control biological activities, such as cell proliferation, morphogenesis, tumorigenesis, and metastasis. She studies the roles of the GTPases Ras and Rac in signal transduction. Cellular Ras genes are frequently activated by mutation in a wide variety of human cancers. Van Aelst has shown that the serine/threonine kinase Raf interacts directly with Ras and is essential for Ras-mediated transformation. Van Aelst’s major objectives are to dissect the physiological roles of Rac and its interacting proteins and to characterize the proteins that mediate the activities of Ras and Rac. To that end, her lab has set out to identify physiologically relevant targets of Ras and Rac and to characterize genetically the different Rac signal-transduction pathways involved in cell-growth control.
(516) 367-8455, vanaelst@cshl.org

Mark Bowen
Assistant Professor, Department of Physiology and Biophysics
Ph. D. Biochemistry University of Illinois at Chicago 1998

Mark's lab is interested in understanding the molecular underpinnings of synaptic transmission. 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. The aim is 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, we come closer to predicting the output of the neuronal signaling network.
Lab: Basic Science Tower 5-121
Contact - (631) 444-2536, Email: mark.bowen(at)sunysb.edu

furie MARTHA B. FURIE, Professor
Ph.D. 1980, The Rockefeller University
Department of Pathology

Martha Furie is a cell biologist who studies the molecular mechanisms that control the inflammatory response. In areas of inflammation, white blood cells leave the bloodstream and enter surrounding tissues, where their excessive accumulation may contribute to tissue injury. To exit from the bloodstream, the white cells must first adhere to and then migrate across the layer of endothelial cells that lines the blood vessel wall. Researchers in the Furie laboratory use tissue culture approaches to identify the factors that initiate and regulate this process. As a member of the interdepartmental Center for Infectious Diseases, she is particularly interested in examining how bacteria interact with host cells to stimulate the inflammatory response. Currently, efforts are focused on understanding how Borrelia burgdorferi, which causes Lyme disease, alters the behavior of endothelial cells and white blood cells to produce the inflammatory symptoms that typify this illness. In addition, the Furie laboratory is studying how host cells interact with Francisella tularensis, a highly virulent bacterium that has been categorized as a potential agent of bioterrorism.
(631) 632-4232, mfurie@notes.cc.stonybrook.edu|
Website - http://miv7.informatics.sunysb.edu/cid/furie.html

kernan MAURICE KERNAN, Associate Professor
Ph.D. 1984, University of Wisconsin
Department of Neurobiology and Behavioral Sciences

Maurice Kernan’s laboratory combines genetic, molecular, and electrophysiological techniques to study the mechanical senses–touch, hearing, and proprioception. Using the fruit fly Drosophila as an experimental system, he focuses on the discovery of novel proteins required for the differentiation and operation of mechanosensory cells and organs. First, behavioral mutants with phenotypes such as touch-insensitivity, deafness, and uncoordination are isolated. Electrophysiological recordings from tactile bristles and from the fly’s antennal ear identify those mutants with transduction defects, and genetic mapping and molecular cloning enable the affected genes and proteins to be isolated and described. Modified genes reintroduced into transgenic flies reveal the location of the encoded proteins in the sense organs. Current projects include studies of an extracellular protein that is required to link nerve endings to external sensory structures and a centriole-associated protein involved in the differentiation of all ciliated neurons and sperm cells.
(631) 632-9964, mkernan@notes.cc.sunysb.edu

hayman MICHAEL J. HAYMAN, Professor
Ph.D. 1973, National Institute of Medical Research, London, England
Department of Molecular Genetics and Microbiology

Michael Hayman’s research focuses on the mechanisms by which growth factor receptors function to control growth, differentiation, and malignant disease and also how oncogenes can cooperate to cause cancer. It has become apparent that growth factor receptors can function as oncogenes and play a causal role in cell transformation and oncogenesis. For example, analysis of human tumors derived from squamous epithelium has shown that the epidermal growth factor receptor (EGFR) is overexpressed, and in chickens mutated forms of the EGFR are frequently transduced into avian retroviruses, giving rise to erythroid leukemias and sarcomas. Hayman’s laboratory is studying the signal transduction pathways activated by the growth factor receptors that are important in these pathogenic states. The model system under analysis studies leukemic cells that are induced to grow by signals from both the nuclear oncogene v-Ski and the oncogenic tyrosine kinase v-Sea. This system allows an analysis of the interaction between nuclear signals and signals from tyrosine kinases in leukemogenesis.
(631) 632 8792, mhayman@ms.cc.sunysb.edu

wigler MICHAEL WIGLER, Professor
Ph.D. 1978, Columbia University
Cold Spring Harbor Laboratory

Michael Wigler examines cancer genes and the proteins involved in signal-transduction pathways. The Wigler lab uses yeast cells and mammalian cells in culture to study these oncogenes. To discover new cancer genes, his lab has developed representational difference analysis (RDA), a method that selects restriction fragments that are present in one of only two DNA populations, or that are more numerous in one than in another. Wigler has used RDA to detect genetic abnormalities that accumulate in the genomes of tumor cells, including DNA amplifications, rearrangements, loss of heterozygosity, and homozygous deletions. Using RDA, he discovered homozygous deletions on chromosome 10, and through positional cloning of this region, identified PTEN, a new tumor-suppressor gene that encodes a protein phosphatase. Wigler’s group is also exploring the combination of representational approaches of genomic analysis and microarray technology to develop methods for high-resolution scanning of the genomes of cancer cells.
(516) 367-8377, wigler@cshl.org

reich NANCY C. REICH, Professor
Ph.D. 1983, Stony Brook University
Department of Molecular Genetics & Microbiology

Studying the molecular mechanisms by which cells respond to hormones or viral infection is the focus of our research. One aspect of study is the physiological response of cells to cytokines. Cytokines bind to cell surface receptors and transmit a signal to the nucleus that activates transcription of a specific set of genes. This signal transduction pathway initiates with the activation of tyrosine kinases and phosphorylation of latent cytoplasmic transcription factors called signal transducers and activators of transcription (STATs). Phosphorylation of the STATs promotes their translocation to the nucleus and binding to specific DNA target sites of induced genes. Another aspect of research is the defense response of cells to viral infection. During infection, viral dsRNA is generated by transcription and/or replication. Our investigations have led to the discovery of a latent transcription factor that is activated by dsRNA. This dsRNA-activated factor directly induces expression of a subset of cellular defense genes. Present work is directed at analyzing the molecular mechanisms that regulate gene expression in response to cytokines or viral infection.
(631) 632-8650, nreich@notes.cc.sunysb.edu

NANCY M. HOLLINGSWORTH, Professor
Ph.D. 1988, University of Washington
Department of Biochemistry and Cell Biology

Nancy Hollingsworth's research is focused on understanding chromosome structure and function during meiosis. Failures in chromosome segregation during meiosis lead to sterility and birth defects in humans. The conservation of the meiotic divisions throughout evolution has allowed the use of model organisms, such as the yeast, Saccharomyces cerevisiae, for gene discovery and functional analyses. The Hollingsworth lab uses a combination of approaches, including genetics, molecular biology,
biochemistry, and cytology to identify genes important for chromosome synapsis, recombination, and segregation, and to determine their functions. Currently the lab is studying how protein phosphorylation by a meiosis-specific kinase, Mek1, suppresses recombination between
sister chromatids during meiosis. In addition, studies using a chemically inhibitable form of the highly evolutionarily kinase, Cdc7, have revealed roles for this kinase in premeiotic DNA
replication, initiation of meiotic recombination and progression through the meiotic divisions.
(631) 632-8581, nhollin@ms.cc.sunysb.edu ,
http://www.sunysb.edu/biochem/hollingsworth/index.html

dean NETA DEAN, Associate Professor
Ph.D. 1988, University of California at Los Angeles
Department of Biochemistry and Cell Biology

Neta Dean’s research focuses on the regulation of glycosylation and cell wall biogenesis in yeast. Glycosylation is an essential modification that functions in a variety of biological roles ranging from the stabilization of protein structure to the regulation of cell surface properties. The research in her laboratory aims to show how this modification is regulated, how glycoproteins mediate their biological roles at the cell surface, and how fungal cell wall biosynthesis is coordinated with growth and division. As a model system for most of these studies, the budding yeast S. cerevisiae is used. Since cell surface carbohydrates are among the primary virulence determinants of pathogenic fungi, a major effort is also underway to understand the regulation of cell surface glycoprotein synthesis in the most frequently isolated human fungal pathogen, Candida albicans.
(631) 632-9309, neta.dean@stonybrook.edu , http://www.sunysb.edu/biochem/dean/index.html

tonks NICHOLAS K. TONKS, Professor
Ph.D. 1985, University of Dundee
Cold Spring Harbor Laboratory

Nicholas Tonk’s research focuses on the phosphorylation of tyrosyl residues in proteins as a key component of the control of many fundamental physiological processes. Phosphorylation is a reversible, dynamic process in which the net level of phosphate observed in a target substrate reflects not only the activity of the kinases that phosphorylate it, but also the competing action of the protein phosphatases that catalyze the dephosphorylation reaction. Tonk’s lab studies the expanding family of protein tyrosine phosphatases (PTPs), which, like the kinases, comprise both transmembrane, receptor-linked forms and nontransmembrane cytosolic species and are now known to be integral components of the regulation of cellular signaling events. The PTPs display diverse structures and properties, which indicate that they may play important roles in the control of proliferation, differentiation, cell adhesion and motility, cytoskeletal function, and the cell cycle.
The lab is integrating a variety of approaches, from protein biochemistry to cell biology and genetics, to define more precisely the physiological function of individual members of the PTP family. One approach in particular allows us to link individual PTPs dephosphorylation of defined pTyr proteins in vivo, thus providing information about physiological function.
(516) 367-8846, tonks@cshl.org

nisson NISSON SCHECHTER, Professor
Ph.D. 1970, Western Michigan University
Department of Psychiatry and Behavior

Research in Nisson Schechter’s laboratory focuses on two homeobox gene proteins, Vsx-1 and Vsx-2, which influence cell differentiation and proliferation during development. These transcription factors are members of a paired-like: CVC subclass of homeobox genes. In situ hybridization indicates that the regulatory roles of Vsx-1 and Vsx-2 differ during early stages of retinogenesis. In contrast, after retinal differentiation, Vsx-1 and Vsx-2 mRNA co-localize in cells of the INL suggesting that these genes are involved in maintaining bipolar cells in their laminar layer. Still under investigation are the mechanisms by which these genes regulate the proliferation, differentiation, and maintenance of specific cells during zebrafish retinal development. Additional studies will determine whether ubiquitination of these transcription factors serves as a post-translational mechanism for regulating their fate during development. A related project is investigating the role of a ubiquitin-like conjugase, Ubc9, in the transport of Vsx-1 and Vsx-2 to the nucleus. All of these experiments utilize the techniques of molecular and cell biology to determine how specific homeobox transcription factors regulate cell fate during development.
(631) 444-1368, nschechter@mail.psychiatry.sunysb.edu

scarlata ORLANDO D. SCHÄRER, Associate Professor
Ph.D. 1996, Harvard University
Departments of Pharmacological Sciences and Chemistry

The Schärer laboratory uses a combination of organic chemistry, biochemistry, molecular and cellular biology to study mammalian DNA repair processes. The goals of this work are 1) to understand how complex biochemical processes operate in mammalian cells; the nucleotide excision repair pathway provides an ideal system for these studies. 2) to understand the molecular basis of the cancer prone genetic disorder xeroderma pigmentosum. 3) to study pathways for the repair of DNA interstrand crosslinks. 4) to find inhibitors of DNA repair pathways that may be used in cancer chemotherapy.
(631)-632-7545; orlando@pharm.stonybrook.edu
Website - Profile | Scharer Lab

tonge PETER J. TONGE, Professor
Ph.D. 1986, University of Birmingham
Department of Chemistry

Peter Tonge’s research focuses on designing, synthesizing and evaluating inhibitors of enzyme drug targets from pathogens such as Mycobacterium tuberculosis and Francisella tularensis. Mechanistic studies on target enzymes involve techniques such as vibrational spectroscopy and NMR spectroscopy, and provide detailed information on 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. In separate studies, 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. Ultrafast time resolved infrared spectroscopy is being used to monitor photoinduced changes in chromophore structure on the picosecond timescale. In addition, native chemical ligation is being used to incorporate unnatural residues into GFP in order to probe the mechanism of chromophore formation.
Contact - (631) 632 7907, Peter.Tonge@stonybrook.edu
Webpage - http://ms.cc.sunysb.edu/~ptonge/

RICHARD LIN, Associate Professor
M.D. 1988, University of California, San Francisco
Departments of Medicine and Physiology & Biophysics, and the Institute of Molecular Cardiology

Richard Lin uses cellular and mouse models to investigate the signal transduction pathways regulating growth and differentiation. Currently his laboratory is focused on understanding the regulation and physiological roles of phosphatidylinositol 3-kinases. These lipid kinases generate second messengers that are implicated in the control of cell growth, apoptosis, transcription, translation, intracellular trafficking of proteins and chemotaxis.
(631) 444-2059, richard.lin@sunysb.edu ,
http://www.uhmc.sunysb.edu/internalmed/hematol/rlin/lin.html

kew RICHARD R. KEW, Associate Professor
Ph.D. 1986, Stony Brook University
Department of Pathology

Richard Kew’s lab is interested in how components of the innate immune system contribute to the pathology of inflammatory diseases. A major focus of the lab is to determine how plasma and cell-derived cofactors regulate the chemotactic signals that direct leukocytes from the blood to sites of inflammation. They have been utilizing cell biological, biochemical, and molecular approaches to investigate the mechanisms by which a ubiquitous, multifunctional plasma protein, known as the vitamin D binding protein (DBP), regulates leukocyte migration to the activated complement peptide C5a, a very potent chemoattractant for a wide variety of cell types. Moreover, complement activation and subsequent generation of C5a has been associated with the pathogenesis of several inflammatory disorders. Therefore, understanding how C5a chemotactic activity is regulated will have major physiological significance. A second major focus of the lab is to determine how mast cell products contribute to tissue remodeling in chronic inflammatory diseases such as rheumatoid arthritis.
(631) 444-3941, rkew@notes.cc.stonybrook.edu

ROLF STERNGLANZ, Professor
Ph.D. 1967, Harvard University
Department of Biochemistry and Cell Biology

Rolf Sternglanz uses the budding yeast, Saccharomyces cerevisiae , to identify mutants and characterize genes affecting structure and function of the nucleus. This includes genes encoding proteins involved in gene regulation, chromatin structure, or DNA replication. Currently the lab is focusing on the mechanism of transcriptional silencing of the mating-type loci (i.e., the yeast equivalent of heterochromatin); identification of genes encoding histone acetyltransferases, deacetylases, and other histone modifying enzymes; and the role of the nuclear periphery in regulation of DNA replication and silencing.
(631) 632-8565, rolf@life.bio.sunysb.edu

simon SANFORD SIMON, Professor
Ph.D. 1967, The Rockefeller University
Department of Biochemistry and Cell Biology

Sanford Simon studies the acute and chronic inflammatory responses that are important host defenses against foreign substances or pathogens. These responses are largely mediated by neutrophils and macrophages, which release proteases, cytokines, and a number of other mediators of inflammation in the course of defending the host. Simon and his lab study the mechanisms of action of serine proteases and metalloproteases from activated neutrophils and develop specific inhibitors to control the tissue destruction which may otherwise injure the host during an inflammatory response. They work with a complete interstitial extracellular matrix from rat smooth muscle cells which they label biosynthetically and employ as a substrate for activated inflammatory cells and their proteases. The lab also allows the smooth muscle cells to deposit their matrix on porous membrane filters, which they then use to study invasive migration of neutrophils and macrophages in response to chemotactic stimuli. To understand how inflammatory cells communicate, Simon studies paracrine mechanisms of activation by cytokines, using immunofluorescence and flow cytometry to measure levels of expression of cell surface receptors and other marker proteins that are sensitive to the state of activation of the cells.
(631) 444-3007, ssimon@path.som.sunysb.edu

SIMON HALEGOUA, Professor
Ph.D. 1978, Stony Brook University
Department of Neurobiology & Behavior

Simon Halegoua's work is aimed at elucidating the mechanisms for spatio-temporal signaling of Neurotrophins to mediate neuronal survival and differentiation. A combination of cell biological and molecular approaches are used in neuronal cell culture paradigms to identify the signaling carriers and effectors as they traverse axons and soma over time. The biochemical and structural correlates of signaling are studied using molecular biology, real time confocal imaging, immuno-electron microscopy, and structural biology.
631-632-8736, simon.halegoua@sunysb.edu

Soosan Ghazizadeh, Associate Professor
Ph.D. 1994, Stony Brook University
Department of Oral Biology and Pathology

Cutaneous gene therapy involves the transfer of new genetic material to skin for the treatment of inherited skin and systemic disorders. However, such a therapy requires development of several new technologies for gene transfer and regulating gene expression as well as new insights into basic stem cell biology. Accordingly, my lab has focused on developing methods and new insights for efficient delivery of the therapeutic gene to long-lived stem cells, for persistent expression of the transgene in stem cells and their progeny, and for avoidance of immune responses to transgene products or vector elements. We have developed in vivo and ex vivo models of cutaneous gene transfer and currently focusing on two projects addressing the critical issues in cutaneous gene therapy; 1) the organization and behavior of stem cells in normal and regenerative cutaneous epithelia, and 2) the host immune responses to transgene expression targeted to skin epithelial cells.
(631) 632-3138, sghazizadeh@notes.cc.sunysb.edu
http://www.hsc.stonybrook.edu/dental/faculty/s_ghazizadeh.cfm.

smith STEVEN O. SMITH, Professor
Ph.D. 1985, University of California at Berkeley
Department of Biochemistry and Cell Biology

Steven Smith is using structural, computational and molecular biological approaches for understanding in chemical terms how membrane proteins function. Current work focuses on the molecular mechanisms of signal transduction by G protein-coupled receptors, receptor tyrosine kinases, and cytokine receptors, as well as on the structure, formation and inhibition of amyloidogenic proteins involved in Alzheimer’s, prion and Huntington’s disease. Research on signal transduction mechanisms mediated by protein conformational changes involves 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 the EGF, FGF and PDGF families of growth factor receptors, and the Epo and Tpo families of cytokine receptors. 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

STUART McLAUGHLIN, Distinguished Professor
Ph.D. 1968, University of British Columbia
Department of Physiology and Biophysics

Stuart McLaughlin is a biophysicist interested in signal transduction. 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, Stuart.McLaughlin@stonybrook.edu

tsirka STYLIANI-ANNA E. TSIRKA, Associate Professor
Ph.D. 1989, Aristotelian University of Thessaloniki, Greece
Department of Pharmacological Sciences, School of Medicine

The focus of Stella Tsirka’s work is the signaling events and cell-to-cell communication after normal or exaggerated stimulation of the central nervous system. When the stimulation is within the physiological levels, it leads to structural changes in the brain (such
as neurite outgrowth or retraction); when the stimulation is overwhelming to the neurons, it leads to neuronal cell death. The experimental system used for neuronal death is excitotoxicity, which models the mechanism of death observed in several neurodegenerative diseases. A handle to study these events is the extracellular serine
protease tissue plasminogen activator (tPA). Tsirka has identified a functional role for tPA—that it promotes neuronal death in the mouse brain. tPA is expressed both by neurons and microglia, and it affects the two cell types using different biochemical pathways. tPA promotes neuronal cell death via its proteolytic activity, but mediates microglia activation via a nonproteolytic pathway. The two cell types interact with each other and the mechanisms of this interaction are being investigated.
(631) 444-3859, stella@pharm.stonybrook.edu

scarlata SUZANNE F. SCARLATA, Associate Professor
Ph.D. 1984, University of Illinois
Department of Physiology and Biophysics

Suzanne Scarlata's laboratory focuses on how heterotrimeric G proteins relay signals in cells. One project in the lab seeks to determine the molecular pathway through which G proteins activate effector proteins, and in particular phospholipase C- b . Both traditional and newly developed fluorescence and theoretical methods are being used in combination with molecular biology and protein chemistry. A second project in the lab focuses on the regulation of G protein signals in living cells. These studies follow the localization, dynamics and interactions between receptors, G proteins, phospholipase C- b and other regulatory proteins using live cell imaging of fluorescent tagged proteins.
Contact - (631) 444-3071, suzanne.scarlata@sunysb.edu

THOMAS W. WHITE, Associate Professor
Ph.D. 1994, Harvard University
Department of Physiology and Biophysics

Thomas White is interested in gap junction functions defined by genetic diseases and gene knockouts. In vertebrates, a large family of genes known as connexins encodes gap junctional channels, and mutations in human connexins underlie a variety of diseases, including deafness, skin diseases (keratodermas), demyelinating 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. Prof. White is interested in how different members of the connexin family fulfill unique functions in tissue homeostasis, and utilize genetically engineered mice to probe the unique communication requirements of different tissues. I also use electrophysiological assays to determine the alterations in channel function that arise from connexin mutations that cause human hereditary disease.
(631) 444-9683, thwhite@notes.cc.sunysb.edu , http://www.pnb.sunysb.edu/faculty/twhite/twhite.htm

moll UTE MOLL, Associate Professor
M.D. 1985, University of Ulm, Germany
Department of Pathology

Research in Ute Moll’s group revolves around the p53 tumor suppressor and related genes, p73 and p63. Concerning p53 regulation in normal cells, the group investigates p53’s requirement for nuclear access that constitutes an important spatial mechanism of regulating p53’s activity as a transcription factor. Moll’s group was recently involved in identifying a novel leucine-rich NES (nuclear export signal) located within the tetramerization domain. This NES can mediate nuclear-cytoplasmic shuttling of p53 in the absence of mdm2 through association with the export receptor CRM1. The model links p53 function with localization. Regulated tetramerization of p53 occludes its NES, thereby ensuring nuclear retention of the active DNA-binding form. Moll and her students discovered a class of inactivating lesions that result in nuclear exclusion of wild type p53 in breast cancer, colon cancer, and neuroblastoma (NB). The group identified the cytoplasmic sequestration not as static but showed that p53 is subject to continuous nuclear-cytoplasmic shuttling with predominant nuclear export (hyperactive export).
(631) 444-2459, umoll@path.som.sunysb.edu

VITALY CITOVSKY, Professor
Ph.D. 1987, Hebrew University, Jerusalem
Department of Biochemistry and Cell Biology

Vitaly Citovsky is a plant biologist whose research utilizes plant pathogens, which are known to pirate the host cellular pathways for their life cycles, as molecular tools to study fundamental questions in plant biology. In our studies of Agrobacterium, a unique bacterium capable of transfer of genetic material between prokaryotic and eukaryotic cells, we identified and characterized the involvement of basic cellular systems, such as nuclear import machinery, targeted proteolysis machinery, targeting of multiprotein complexes to the cell chromatin, and DNA repair machinery, in the nuclear and intranuclear transport and integration of the invading T-DNA. We also identified and characterized bacterial virulence proteins that interact with these plant systems and may mimic some of their functions. Consistent with the basic, evolutionarily-conserved nature of the host processes required for genetic transformation by Agrobacterium, we demonstrated that this plant pathogen can in fact genetically transform human cells. In our studies of intercellular movement plant viruses, we discovered that viral genomes most likely travel between cells as sub-viral complexes composed mainly of the viral genomic molecule and the viral cell-to-cell movement protein. We then identified numerous cellular proteins that interact with the viral movement protein and likely control the process of the viral transport through plant intercellular connections, the plasmodesmata. Presently, we are expanding our interests in chromatin targeting to the studies of structure, composition, and function of plant corepressor complexes involved in histone modification and chromatin remodeling. In addition, our laboratory is involved in development of novel research tools and approaches for plant functional genomics.
(631) 632-9534, Vitaly.Citovsky@stonybrook.edu

VIVEK MITTAL, Assistant Professor
Ph.D. 1994, Jawaharlal Nehru University
Cancer Genome Research Center
Vivek Mittal uses mouse genetic models and cutting edge functional genomic methods
to understand the role of the bone marrow in angiogenesis-mediated tumor growth and metastasis.
(516)422-4075, mittal@cshl.edu, http://vivemittal.googlepages.com/home

miller W. TODD MILLER, Professor
Ph.D. 1989, The Rockefeller University
Department of Physiology and Biophysics

The focus of research in Todd Miller’s laboratory is the specificity of signalling 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: (1) to understand how tyrosine kinases recognize their target proteins in cells; (2) to determine how these enzymes are regulated in normal cells; and (3) to develop strategies to block the action of oncogenic tyrosine kinases. The laboratory primarily uses biochemical strategies to investigate tyrosine kinase structure and function.
Contact - (631) 444-3533, todd.miller@stonybrook.edu
Miller Laboratory : http://www.pnb.sunysb.edu/faculty/miller/miller.htm

karzai WALI KARZAI, Associate Professor
Ph.D. 1995, Johns Hopkins University
Department of Biochemistry and Cell Biology

Wali Karzai is interested in studying RNA-protein interactions and translational control of gene expression. The major focus of his research is on the SmpBoSsrA quality control system for protein tagging, directed degradation, and ribosome rescue. His laboratory is also interested in understanding how sequence and structure in RNA-binding proteins contribute to the formation of specific RNA-protein complexes and how these complexes promote specific biological functions. He uses a combination of protein biochemistry, functional genomics, bioinformatics, and X-ray crystallography to determine the biological function and mechanism of action of specific RNA-protein complexes.
Contact - (631) 632-1688, akarzai@ms.cc.sunysb.edu
Profile - http://www.stonybrook.edu/biochem/karzai/index.html

wimmer Wei-Xing Zong , Assistant Professor
Ph.D. 1999, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey
Department of Molecular Genetics & Microbiology

Molecular regulation of multiple cell death pathways in cancer development and treatment . A main strategy for treating cancer is to induce cell death. It is often stated as fact that chemotherapies induce death through apoptotic mechanisms. The significance of p53 and the Bcl-2 family and other molecules that drive apoptosis has provided the mort opportunities for pharmaceutical exploitation. With the development of the approaches specifically targeting the impaired apoptosis in cancer cells, however, a paradox in medical oncology has long exist that although the majority of human cancers have acquired a deficiency in apoptosis through p53 mutations or Bcl-2 dysregulation, certain chemotherapeutic agents such as DNA alkylating agents remain the most effective means in curing cancer patients by inducing cancer cell death. This suggests that alternative cell death pathways independent of apoptosis may be involved in cell death induced by chemotherapeutic treatment. These include necrosis, autophagy, and cell senescence. Using cell culture systems and animal tumor models, we study how cell death pathways are regulated, and how they interplay in response to the treatment of anti-cancer drugs.
631-632-4104 , wzong@notes.cc.sunysb.edu , http://www.mgm.stonybrook.edu/zong/index.shtm

chen WEN-TIEN CHEN, Professor
Ph.D. 1979, Yale University
Department of Medicine, Division of Hematology/Oncology

Wen-Tien Chen is a cell biologist whose research focus is on the control of cancer spreading or metastasis. He would like to understand how cancer spreads and what macromolecules or compounds inhibit it. He has been working on new methods of detecting and isolating metastatic cells, measuring their invasiveness, defining their gene expression profiles, and screening anti-metastatic compounds. Wen-Tien has defined an invasive cell surface ultrastructure, called invadopodia, and discovered molecules involved in invadopodial activities, including seprase, dipeptidyl peptidase IV, uPA, MT1-MMP, integrins and cytoskeletal tyrosine kinases.
(631) 444-6948, wenchen@notes.cc.sunysb.edu

WILLIAM E. VAN NOSTRAND, Professor
Ph.D. 1985, University of California at Irvine
Department of Medicine

William Van Nostrand’s research focuses on the pathological condition of cerebrovascular amyloid ß-protein deposition, also known as cerebral amyloid angiopathy, which is a characteristic of Alzheimer’s disease and related disorders. Although cerebral amyloid angiopathy may contribute to the neuronal degeneration in Alzheimer’s disease and can lead to hemorrhagic strokes in afflicted individuals, little is known about how this occurs. The aim of Van Nostrand’s work is to further elucidate the pathogenic mechanisms involved with this pathological condition. To this end, his investigative efforts involve the use of unique in vitro cell culture systems and the development of transgenic mouse models for cerebral amyloid angiopathy. In addition, the effects of cerebrovascular amyloid ß-protein, and its precursor molecule, on the regulation of hemostasis enzymes and reactions are a central theme in his laboratory. Through his research, Van Nostrand has the goal of developing novel approaches to prevent or inhibit the progression of this pathological condition.
(631) 444-1661, wevn@mail.som.sunysb.edu

WILLIAM TANSEY, Associate Professor
Ph.D. 1991, University of Sydney, Australia
Cold Spring Harbor Laboratory

William Tansey researches the fundamental aspects of transcription factor regulation and cell cycle control, focusing on how these processes go awry in cancer. Research in Tansey’s lab centers on discovering mechanisms by which transcription factors are destroyed. Many of the transcription factors involved in cell proliferation are short-lived proteins that are constantly synthesized and then degraded rapidly by ubiquitin-mediated proteolysis. Rapid destruction of these
potent transcription factors allows their activity to be maintained at levels appropriate for controlled cell proliferation. As a paradigm for the regulated destruction of transcription factors, Tansey studies
the product of the Myc oncogene, because it is an important human oncoprotein that directly activates genes required for cell cycle progression. Since little is known about how Myc is destroyed in vivo,
Tansey’s group seeks to identify the cellular machinery that targets Myc for ubiquitin-mediated destruction and to learn how the regulation of Myc turnover and the loss of control of this process relates to human cancer.
(516) 367-8455, tansey@cshl.org

YURI LAZEBNIK, Professor
Ph.D. 1986, St. Petersburg State University, Russia
Cold Spring Harbor Laboratory

Yuri Lazebnik’s laboratory focuses on understanding how cells become cancerous, how cancer cells evolve, and how they can be killed selectively. To understand how cells become cancerous and how they evolve, we explore a model that cell fusion is a co-factor in carcinogenesis and tumor progression. This model argues that fusion of cells whose cell cycle is deregulated produces unstable hybrids that by chance may acquire carcinogenic properties. The cancer cells may further evolve by fusing to normal cells, thereby producing hybrids with additional properties, including the ability to form metastases. We focus on common viruses, many of which are fusogenic, as a cause of cell fusion in the body. To understand how to kill cancer cells selectively, we explore a model that oncogenic transformation induces apoptosis, but that this link is disabled in cancer cells. The idea is that by learning how to restore this link we may understand how to kill cancer cells selectively.
(516) 367-8357, lazebnik@cshl.edu

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