Our Distinguished Faculty

There are currently 30 faculty members in the Biochemistry and Structural Biology Program representing five academic departments at Stony Brook as well as Brookhaven National Laboratory. The common thread that brings this group together is the goal of understanding biological processes at the molecular level. The program faculty are internationally renowned and include members of the National Academy of Sciences. Among the comprehensive faculty interests are the chemical basis of enzyme action (proteinase chemistry, hydrolysis of neurotransmitters); carcinogenesis and DNA repair; structure of membranes and their components (proteins, lipids, glycoproteins, caveolae); carbohydrate biochemistry; second messenger signaling and signal transduction; growth factors; drug design; the structure of ion channels; mouse development; ubiqutin-dependent protein degradation; protein folding; mammalian fertilization; yeast geneics; and biomolecular modeling.

CARL ANDERSON , Associate Professor
Ph.D. 1970, Washington University, St. Louis, MO
Department of Biology, Brookhaven National Laboratory

Carl Anderson discovered the DNA-dependent protein kinase, DNA-PK, which is required for non-homologous end-joining (NHEJ) repair of DNA double strand breaks and has worked extensively on the role of posttranslational modifications in the cellular response to DNA damage, especially as related to the function of the p53 tumor antigen transcription factor. His current efforts are directed at i) understanding the roles of individual posttranslational modification in regulating p53 activity and stability, and characterizing the genotoxic and non-genotoxic stress pathways that regulate p53 activity, and 2) a whole genome analysis of the chromosomal sites bound by p53 using a newly developed high throughput DNA sequencing approaches. Further information is available at http://www.biology.bnl.gov/cellbio/anderson.html

 

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



JAMES V. STAROS, Professor
Ph.D. Department of Biochemistry & Cell Biology
Dean of the College of Arts and Sciences

Molecular mechanisms of transmembrane signaling - Protein chemical studies in our laboratory showed more than twenty years ago that the EGF receptor and the EGF-stimulable Tyr-specific protein kinase are two functions of a single molecule, making the EGF receptor the first recognized member of the superfamily of receptor tyrosine kinases. Using affinity labeling methods, we identified Lys721 as an important residue in the kinase active site. Subsequently, using site-directed mutagenesis, we showed that Asp813 functions as the catalytic base of the kinase in phosphoryl transfer. A surprising outcome of these studies was that the kinase-negative mutant receptors with Asp813 replaced with Ala or Lys 721 replaced with Arg, when expressed in cells without endogenous EGF receptors, are still capable of signaling for DNA replication, but only if ErbB2 is present. When the EGF receptor is expressed in 32D cells, a cell line that normally requires interleukin-3 (IL-3) for survival and proliferation and is devoid of endogenous ErbB receptors, EGF binding to the wild-type receptor can replace the functions of IL-3 binding to the IL-3 receptor. In the absence of EGF, the EGF receptor prevents apoptosis in these cells. Unexpectedly, the kinase-negative mutant in which Lys721 is replaced with Arg also prevents apoptosis; however, the kinase-negative mutant with Asp813 replaced with Ala does not retain this function.
Contact - 631-632-6976 , james.staros@stonybrook.edu
Website - http://www.sunysb.edu/biochem/staros/index.html

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.
Contact - (631) 632-7935, isaac.carrico@sunysb.edu
Carrico Research Group : http://ms.cc.sunysb.edu/%7Eicarrico/Home.html

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

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 sthey affects mood, memory, pain, appetite, response to stress, and many other physiological processes. His 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 he has undertaken basic research to understand how FAAH works to regulate anandamide levels. With the long-term goal of developing drugs to regulate the endocannabinoids, he 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. He 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 animals. Most recently he has 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, Dale.Deutsch@stonybrook.edu

 

DAX FU, Assistant Professor
Ph.D. 1996, Mayo Graduate School of Medicine
Department of Biology, Brookhaven National Laboratory

Channels and transporters are two major classes of integral membrane proteins that mediate regulated passages of ions and solutes across biomembranes. Dax Fu’s research focus is to determine structures of representative channel and transporter proteins in order to elucidate the chemical basis of transmembrane active processes. X-ray crystallography is the tool of structural determination and the cornerstone on which the Fu laboratory will build their research program on two fronts. Theoretically, they will formulate plans to describe dynamics and energetics of transmembrane movements of ions and solutes. Practically, they will carry out structure-based drug design targeting disorders of transmembrane functions. Toward these ends, Fu and his team are developing a general approach for crystallization of integral membrane proteins using multidisciplinary techniques of protein chemistry, molecular biology, and membrane biophysics.
Contact - (631) 344-4208, dax@bnl.gov

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 past 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.
Contact - (631) 632-9030, pgergen@life.bio.sunysb.edu



DAVID F. GREEN, Assistant Professor
Ph.D. 2002, MIT

David Green's research involves computational and theoretical methods to study the specificity of protein-protein interactions. Rather than restricting his studies to biophysical descriptions of protein-protein binding, David is taking an integrated systems biology David's work focuses on the model system of heterotrimeric G-proteins to address a broad range of cellular activities. He is working to identify the interactions which lead to high specificity or promiscuity between families of structurally related proteins, describe the possible modes of evolution of a single binding pair into a family of interacting proteins and develop computation methodologies for the design of specifically interacting proteins. The ramifications of theses molecular-level events on the behavior of the system as a whole is a key area of interest.
Contact - (631) 632-9344, dfgreen@ams.sunysb.edu



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/




ROBERT S. HALTIWANGER, Associate Professor
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

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.
Contact - (631) 632-8292, holdener@life.bio.sunysb.edu

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. Hsieh’s 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 among 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.
Contact - (631) 632-1663, jhsieh@ms.cc.sunysb.edu

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



WILLIAM J. LENNARZ, 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, Lennarz is studying the enzyme that catalyzes folding and disulfide bond formation in glycoproteins.
Contact - (631) 632-8560, William.Lennarz@stonybrook.edu
Website - http://ws.cc.stonybrook.edu/biochem/lennarz/index.html



HUILIN LI, Associate Professor
Ph.D. 1994, University of Science and Technology Beijing
Department of Biology, Brookhaven National Laboratory

Huilin Li uses both cryo-electron microscopy and X-ray crystallography to study the structure and function of several large and important protein assemblies. One such assembly is the origin recognition complex of Saccharomyces cerevisiae that is involved in initiating chromosome replication. The second assembly on which his lab is focusing is the proteasome and proteasomal ATPase of Mycobacterium tuberculosis that are required for TB resistance to macrophage killing by reactive nitric oxide. His lab also studies the structures of large membrane protein complexes, such as the gamma-secretase and the oligosaccharyl transferase.
Contact - (631) 344-2931, hli@bnl.gov , http://www.biology.bnl.gov/structure/li.html



CHANG-JUN LIU, Associate Professor
Ph. D. 1999, Shanghai Institute of Plant Physiology,
the Chinese Academy of Sciences
Department of Biology, Brookhaven National Laboratory

Chang-Jun Liu’s research focuses on the biochemistry and molecular regulation of plant phenylpropanoid biosynthesis and plant cell wall lignocellulosic modifications. Phenylpropanoid metabolism leads to the formation of various phenolics that impart plant structural integrity (lignin), and modulate plant defense responses and plant-environmental interactions (flavonoids and isoflavonoid); while cell wall lignocelluloses (polysaccharides and lignin) constitute the most abundant renewable biomass in the world. Two types of enzymatic reactions, O-methylation and O-acylation commonly occur in the biogenesis and modification of cell wall lignocelluloses, and in the formation of a variety of phenylpropanoids. Through the integrated biochemical genomics approaches, C.J Liu’s group is systemically characterizing the enzymes responsible for the O-methyl- and acyl-esterification of cell wall lignocelluloses and the other related phenolics; they are also exploring the structure-function relationships of these key enzymes by using X-ray crystallographic and protein engineering approaches. Furthermore, they are applying molecular genetic strategies to dissect the biological functions of these two types of esterifications in cell wall biogenesis and phenylpropanoid metabolism.
Contact 631-344-2966, cliu@bnl.gov
Website : http://www.biology.bnl.gov/plantbio/liu.html

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

STUART McLAUGHLIN, 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.
Contact - (631) 444-3615, smcl@epo.som.sunysb.edu

LISA MILLER, Associate Professor
Ph.D. 1995, Albert Einstein College of Medicine
Department of , Brookhaven National Laboratory

isa Miller's research focuses on the study of the chemical makeup of tissue in disease using high-resolution infrared and x-ray imaging at the NSLS. Her work has two primary research areas: (1) examination of the chemical composition of bone tissue in diseases such as osteoarthritis and osteoporosis, and (2) correlation of metal ion content and protein structure in brain tissue in protein-folding diseases such as Alzheimer's disease and scrapie.
Contact - (631) 344-2091, lmiller@bnl.gov
http://infrared.nsls.bnl.gov/u10b/research/default.htm

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

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.
Contact - (631) 632-1543, Aaron.Neiman@sunysb.edu,
http://www.stonybrook.edu/biochem/neiman/index.html

DANIEL P. RALEIGH, Assistant Professor
Ph.D. 1988, Massachusetts Institute of Technology
Department of Chemistry

The Raleigh laboratory is interested in fundamental questions in structural biology. The research is centered upon studies of protein folding, protein structure, and the mechanism of amyloid formation. An understanding of how proteins fold and of the nature of the interactions required to confer a unique stable folded structure, the protein folding problem, is one of the central objects of modern biochemistry. Key questions under investigation include the nature of the early stages of the protein folding process, the role of electrostatic interactions in folding, and the nature and structure of partially folded states of proteins. The pathological processes of protein misfolding, which leads to amyloid formation, is also under investigation. Amyloid formation has been implicated in more than 15 different human diseases and the work in the Raleigh lab is centered or studies of amyloid formation in type-II diabetes.
Contact - (631) 632-9547, Daniel.Raleigh@stonybrook.edu

ROBERT RIZZO, Associate Professor
Department of Applied Mathematics and Statistics
Ph.D. 2001, Yale University

Under the broad category of “Computational Structural Biology” the Rizzo research group seeks to understand the basis for molecular recognition at the atomic level for specific biological systems involved in human disease, such as influenza, SARS, and HIV/AIDS, with the ultimate goal of developing new and improved drugs. Computation is used to model how drugs (typically small molecules) interact with a given receptor (typically a protein). The resultant 3D atomic level structural and energetic information from the calculations can be used to quantify and rationalize drug-binding for known systems and to make predictions for new ones. The research is geared towards developing improved methods and computational tools for estimating binding energies and for virtual screening (docking) calculations which facilitate structure-based design. The research is very interdisciplinary and encompasses not only Applied Mathematics and Statistics, but Biochemistry, Informatics, and Computer Science/Programming. The group has active collaborations with researchers here at Stony Brook, Brookhaven National Laboratory, and the University of California at San Francisco .
Contact - (631)632-9340,rizzo@ams.sunysb.edu,
http://www.ams.sunysb.edu/%7Erizzo/StonyBrook/index.html



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. His research area is in the developmental biology of the fruit fly, Drosophila melanogaster . During the first 90 minutes of life, the cells in the developing fly embryo acquire specific developmental fates in a very precise spatial pattern. This physical organization is the result of differential gene expression among a mutually interacting network of genes. Reinitz's research is focused on characterizing the dynamics of this genetic network. To examine these dynamics, he uses mathematical models, quantitative, gene expression done from his laboratory in the Center for Developmental Genetics and extensive computer simulations that involve state-of-the-art computational science.
Contact - (631) 632-8352, reinitz@ams.sunysb.edu
The Reinitz Fly Lab : http://flyex.ams.sunysb.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 bioorganic 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.
Contact - (631) 632-7952, Nicole.Sampson@stonybrook.edu


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


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



JöRG SCHWENDER , Associate Professor
Ph. D. 1999, University of Karlsruhe , Germany
Department of Biology, Brookhaven National Laboratory

Dr. Schwender’s research is focused on metabolic flux analysis and pathway analysis in plants by employing labeling experiments, mathematical models and computer simulation to describe and analyze metabolism quantitatively. The goal is to better understand how the different biochemical reactions in a cell contribute to the metabolic output like seed storage products in seeds. How does such a network of metabolic reactions maintain its performance under changed nutritional/environmental conditions ? His team use steady-state stable isotope labeling to determine flux ratios through branch points of metabolism. Brassica napus or Arabidopsis thaliana embryos are labeled with a variety of 13C-labeled precursors and individual C-atoms are traced through the metabolic network by analyzing the label in metabolites and end products by GC/MS and NMR. This methodology can investigate fluxes in vivo in systems unperturbed by cell disruption, mutation or transgenes. A particular challenge in plants is the sub-cellular compartmentation of enzymes and substrates.
Contact - (631) 344-3797, schwend@bnl.gov ,
http://www.biology.bnl.gov/plantbio/schwender.html



JOHN SHANKLIN, Research Scientist
Ph.D. 1988, University of Wisconsin at Madison
Department of Biology, Brookhaven National Laboratory

John Shanklin’s research focuses on the biochemistry of lipid modification enzymes. Lipids are one of the functional components of all living things. Despite their importance, the details of lipid synthesis and modification are incomplete. Lipids are first synthesized as saturated fatty acids and double bonds are incorporated post-synthetically by enzymes known as fatty acid desaturases. Desaturation of a fatty acid produces dramatic effects on the physical properties of both cell membranes and storage lipids. The Shanklin lab is performing structure-function analysis on the soluble plant delta-9 stearoyl-ACP desaturase using molecular biochemical and crystallographic approaches. They are also investigating a series of positional and chain length specific isoforms of this enzyme in order to determine the structural basis of these differences. The Shanklin team is in the process of engineering desaturase enzymes with desired specificities. A second, related project, focuses on the characterization of active site components of the major class of fatty acid desaturases that are integral membrane proteins. In recent studies Shanklin has defined the determinants of functional outcome in terms of desaturation or hydroxylation for this class of enzymes.
Contact - (631) 344-3414, shanklin@bnl.gov

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


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

Acute and chronic inflammatory responses 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. Sanford Simon’s laboratory studies the mechanisms of action of serine proteases and metalloproteases from activated neutrophils and develops specific inhibitors to control the tissue destruction that may otherwise injure the host during an inflammatory response. Their methods include biophysical probes of enzyme active sites and kinetic measurements. Simon also works with a complete interstitial extracellular matrix from rat smooth muscle cells, which he labels biosynthetically and employs 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 we then use to study invasive migration of neutrophils and macrophages in response to chemotactic stimuli. To understand how inflammatory cells communicate, we study 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. Simon also measures neutrophil and macrophage phagocytic activity and release of oxidants by flow cytometry. Contact - (631) 444-3007, ssimon@path.som.sunysb.edu


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

Steven Smith uses structural 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 and receptor tyrosine kinases, and the mechanism of selectivity and gating by ion channel proteins. 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. Projects involving signal transduction mediated by receptor oligomerization focus on two receptor proteins—the neuorerbB-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.
Contact - (631) 632-1210, Steven.O.Smith@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, DNA replication, or chromatin structure. The Sternglanz lab is focused on the mechanism of transcriptional silencing of the mating-type loci (i.e., a study of 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.
Contact - (631) 632-8565, rolf@life.bio.sunysb.edu


SUBRAMANYAM SWAMINATHAN , Associate Professor
Department of Biology, Brookhaven National Laboratory

 

 

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.
Contact - (631) 632-8536, gthomsen@notes.cc.stonybrook.edu

PETER J. TONGE, Professor
Ph.D. 1986, University of Birmingham
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. Currently, drug-design efforts are focused on an enzyme from Mycobacterium tuberculosis, which is a target for the antitubercular drug isoniazid. 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 using approaches that include ultrafast vibrational spectroscopy.
Contact - (631) 632 7907, Peter.Tonge@stonybrook.edu
Website - http://ms.cc.sunysb.edu/~ptonge/

JIN WANG, Associate Professor
Ph.D. 1991, University of Illinois

The main concentration of Jin Wang’s research is on the study of the fundamental mechanism of biomolecular folding, especially a protein folding. Using modern statistical mechanics and empirical information from protein databases, an energy landscape of protein folding can be obtained. By further studying the detailed structure of the landscape, the fundamental questions such as nucleation of protein folding can be answered for different proteins. The results of the study can be compared with the experiments. The energy landscape description of protein folding will also provide insight of new algorithms of structure prediction and protein design. Another focus of Wang’s study is the reaction dynamics in complex environments, specifically biomolecular reactions and interactions in which the reaction happens in a relatively fast or comparable time scale relative to the environmental fluctuations. A path integral formalism is developed for the full treatment of the problem. Potential application of this method includes electron transfer in proteins, ligand binding, and reaction dynamics in complex solvents. Wang is also interested in the study of single molecule reaction dynamics, which provides a detailed picture of molecular reactions without an ensemble average.
Contact - (631) 632-1185, jin.wang@stonybrook.com

 

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