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Guy M. Benian, M.D. Pathology and Laboratory Medicine pathgb@emory.edu Faculty Website: http://pathology.emory.edu/AdminFacultyMember.cfm?Name_seq=6 Muscle and cytoskeleton in C. elegans. The sarcomere performs the work of muscle contraction and is a highly ordered assemblage of several hundred proteins. Despite increasing knowledge of the components and functions of sarcomeric proteins (new ones are discovered each year!), we still don't understand how sarcomeres are assembled, and maintained. Our lab is studying these questions in the model genetic organism, C. elegans. We focus on two questions: (1) What are the structures and functions of the giant muscle proteins (>700,000 Da)? (2) What are the molecular mechanisms by which sarcomeres are attached to the muscle cell membrane and transmit force? The giant muscle proteins consist primarily of multiple copies of immunoglobulin (Ig) and fibronectin type 3 (Fn3) domains, and one or even two protein kinase domains. C. elegans has 3 such proteins: twitchin (754,000 Da, located in the A-band, and probably regulating muscle relaxation), TTN-1 (2.2 MDa, located in the I-band and perhaps acting as a molecular spring), and UNC-89 (up to 900,000 Da, a homolog of the human protein "obscurin", and having roles in M-line assembly and integration with the SR). One goal is to identify proteins that interact with these giants that explains their localization and their functions. Other goals including learning the substrates of the protein kinase domains, and to understand how the normally "autoinhibited" kinase domains become activated. We are also defining complex protein interaction networks at muscle attachment sites. One project is to test the hypothesis that the localization of one of these proteins, UNC-112 (kindlin in humans), is regulated by an interaction with PAT-4 (ILK), which promotes a conformational change in UNC-112.

Jeremy M. Boss, Ph.D. Microbiology & Immunology jmboss@emory.edu Faculty Website: http://www.microbiology.emory.edu/boss/ Molecular immunology; regulation of major histocompatibility complex class II genes and tumor necrosis factor gene induction. Overlying simple gene regulatory mechanisms is the local chromatin architecture that controls the accessibility of a gene to specific transcription factors. Our lab investigates the role of chromatin in the regulation of genes in the immune system. In our model systems, we seek to elucidate the events that control major histocompatibility complex class II (MHC-II) genes and genes regulated by tumor necrosis factor. We employ animal, cellular, and molecular approaches in our studies. Key questions include understanding how transcription factors modify chromatin structure and how transcription factors interact over long distances to activate gene expression. Mice containing deleted regulatory elements are being created to develop in vivo model systems to interrogate gene assembly and chromatin modification questions. Through this type of analysis we hope to develop higher order models of gene regulation, through which specific factors may be targeted for immune based therapies used in infectious disease, autoimmunity, and vaccination.

Tamara Caspary, Ph.D. Human Genetics tcaspar@emory.edu Faculty Website: http://www.genetics.emory.edu/labs/caspary/caspary_lab_index.php Developmental Biology: Identification and functional analysis of previously uncharacterized genes important in mammalian development through forward genetic screens in the mouse. We ask directly which genes are important in mammalian development by performing unbiased screens in the mouse. We have identified several mutant lines with defects in neural development and in establishing a proper left-right body axis. Once we identify the novel proteins we combine molecular, cellular and genetic approaches to define the molecular mechanisms that cause cells to make specific cell fate decisions. For example, one current area of focus is a protein we identified called Arl13b whose loss results in abnormal cilia as well as abnormal motor neuron and oligodendrocyte cell specification. As all eukaryotic cells, including neurons, have a cilium we are interested in understanding the mechanistic link between cilia structure, cell signaling and proper specification of neurons. Through approaches including gene targeting, in vitro differentiation of embryonic stem cells, in vivo imaging of endogenous and tagged proteins and protein-protein interaction studies, we aim to better understand how cell signaling works to elaborate the mammalian body plan.

Anthony W.S. Chan, DVM Ph.D. Human Genetics awchan@emory.edu Faculty Website: http://genetics.emory.edu/faculty/faculty.php?facultyid=149 Transgenic stem cell cloning and assisted reproductive technologies in disease modeling. My lab focuses on the development of genetically modified nonhuman primate model of human hereditary diseases such as Huntington's, Alzheimer's and Parkinson's etc. We are interest in developing transgenic monkeys that mimics patient genetic and pathologic alterations. These monkeys will be used for the understanding of disease development and the development of treatments. Additionally, somatic cell cloning, embryonic stem cell and reproductive technology are also developing in the lab, which is critical for the development cell replacement therapy. In order to achieve this goal, we investigate embryonic reprogramming in cloned embryo, epigenetic control in embryonic gene expression and differentiation process, viral and non-viral gene transfer, gamete and gonad cryopreservation and in vitro differentiation of embryonic stem cells.

Ping Chen, Ph.D. Cell Biology pchen@emory.edu Faculty Website: http://cellbio.emory.edu/lab/chen/ Planar cell polarity signaling in vertebrates Cellular polarization is a fundamental issue in developmental and cell biology. In particular, planar cell polarity (PCP) refers to coordinated polarization of cells within the plane of a cell sheet. PCP signaling is required for establishing epithelial PCP, such as uniformed orientation of sensory cells in the inner ear. In addition, PCP signaling drives a type of cell movement known as convergent extension (CE) that is essential for establishment of body axes and germ layers during gastrulation and for neural tube extension and closure. Our lab uses a combination of genetic model systems and in vitro cultures to dissect PCP signaling in vertebrates. Our favorite genetic model is the mouse auditory sensory organ. The mammalian auditory organ consists of precisely aligned sensory and nonsensory cells, providing a unique system for analyzing cellular patterning and polarity. In addition, we have started to explore the zebrafish system and examine multiple PCP-regulated cellular processes, such as gastrulation, neurulation, establishment of CPP in the lateral line and the inner ear.

Xiaodong Cheng, Ph.D. Biochemistry xcheng@emory.edu Faculty Website: http://www.biochem.emory.edu/cgi-bin/people/detail_faculty?id=xcheng Epigenetic link between DNA methylation and histone modifications Dr. Cheng’s current work focuses on epigenetic link between DNA methylation and histone modifications. Dr. Cheng’s group determined the first structure of a protein arginine methyltransferase (2000 EMBO J), the first structure of a histone lysine methyltransferase (2002 Cell), established a switch mechanism of Phe/Tyr (phenylalanine/tyrosine) in controlling the degree of lysine methylation by one, two or three methyl groups (2003 Mol. Cell), and illustrated the transition from nonspecific to specific DNA interaction along the substrate recognition pathway by a DNA methyltransferase (2005 Cell). In collaboration with a group of scientists, Dr. Cheng’s group used elegant structural and biochemical analyses that provide insights into the long-standing question of how imprinted genes are targeted for DNA methylation (2007 three Nature papers). They revealed a novel mechanism of converting patterns of histone methylation into patterns of DNA methylation that mediate the heritable silencing, and the underlying DNA sequences of imprinted genes also contribute to the establishment of heritable methylation patterns. More recently, his group demonstrated that an ankyrin repeat domain bind selectively to mono- and dimethylated lysine 9 of histone H3 (2008 Nature Structural & Molecular Biology), a recognition of hemi-methylated CpG by SRA domain using a base-flipping mechanism (2009 Nature), and a structural basis for inhibition of G9a protein lysine methyltransferase by BIX-01294 (2009 Nature Structural & Molecular Biology).

Anita H. Corbett, Ph.D. Biochemistry acorbe2@emory.edu Faculty Website: http://www.biochem.emory.edu/labs/acorbe2/index.html Interplay between nucleocytoplasmic transport and cell-cycle progression in yeast. Nucleocytoplasmic transport is a critical element of virtually all signal transduction pathways. Classical signal transduction consists of a signal that originates outside the cell and is ultimately transduced into the nucleus often in the form of import of a transcription factor. Many common cellular responses to signals rely on the transcriptional upregulation of specific genes. The newly synthesized messenger RNA must then be exported from the nucleus to the cytoplasm. All macromolecules that cross the nuclear envelope move through large protein channels termed nuclear pores. Recent studies have found that in addition to the nuclear pores a number of soluble factors are required both for targeting substrates to the nuclear pore and for translocation across the pore. Our work focuses on understanding the detailed mechanisms of protein transport into and out of the nucleus and mRNA export from the nucleus.

Victor G. Corces, Ph.D. Biology vcorces@emory.edu Faculty Website: http://www.biology.emory.edu/research/Corces/ The goal of our research is to understand epigenetic mechanisms controlling the expression of eukaryotic genes. The main focus of our lab is to study the organization of the chromatin fiber within the eukaryotic nucleus and the mechanisms controlling this organization. Sequences involved in the establishment of this organization are called chromatin insulators. We have identified several different proteins that form a complex with insulator DNA and we are in the process of analyzing their function. The working hypothesis we are currently testing is that insulators are responsible for controlling patterns of nuclear organization required for cell differentiation. Alterations in insulator function that disrupt this organization could lead to cancer and other diseases. We are also interested in the role of the primary structure of the chromatin fiber, as determined by histone tail modification, in the regulation of transcription. In particular, we have found that phosphorylation of hitone H3 is an essential step during the promoter clearance process in the transcription of all Drosophila genes. The levels of phosphorylated histone H3 are maintained by a balance between the activities of the JIL-1 kinase and the PP2A protein phosphatase. We are currently exploring the mechanisms by which the activity of these two enzymes is regulated to control chromatin structure and transcription.

Gray F. Crouse, Ph.D. Biology gcrouse@emory.edu Faculty Website: http://www.biology.emory.edu/index.cfm?faculty=23 Molecular genetics; DNA repair and recombination in yeast and mouse. Research in my lab centers on DNA repair in eukaryotic cells. We focus on the DNA mismatch repair system (MMR), which has been of great interest since the discovery of its central role in preventing colon cancer in humans. My lab was the first to clone a MMR gene in eukaryotes: the mouse Msh3 gene, but we now spend most of our time studying MMR in yeast because of the great number of genetic tools for yeast work and the relative ease with which we can do experiments that are impossible in bigger eukaryotes. We are studying the way in which MMR prevents mutations and blocks recombination between nonidentical sequences and the interplay between MMR, replication, and translesion synthesis.

Joseph Cubells, Ph.D. Human Genetics jcubell@emory.edu Faculty Website: http://genetics.emory.edu/faculty/faculty.php?facultyid=396 Research in this laboratory focuses on genetic contributions to human behavioral disorders including schizophrenia, major depression, PTSD, autism, and the 22q11 deletion syndrome. Part of the focus on such disorders is to understand in detail the genetics of relevant simpler traits ("endophenotypes"), including plasma activity of dopamine ?-hydroxylase and the human startle response. Another area of focus is candidate-gene analysis, with an emphasis on genotyping sufficient polymorphisms to account for most of the common variation at the locus. The following projects are currently funded: Linkage analysis of schizophrenia, conditional on plasma DBH activity and DBH genotypes. Longitudinal behavioral analysis of adolescents and young adults with 22q11DS. Analysis of glucocorticpid-receptor-related chaperone and co-chaperone gene expression in women with pregnancy-related major depression. Candidate gene analysis in civilian post-traumatic stress disorder.

Roger Deal, Ph.D. Biology roger.deal@emory.edu Faculty Website: http://www.biology.emory.edu/index.cfm?name=Roger-Deal&faculty=339 Transcriptional regulation, epigenetics, and cell differentiation. Our work is directed toward understanding the fundamental mechanisms of chromatin-based gene regulation, and elucidating how these mechanisms are used to shape the gene expression profiles of individual cell types during cell differentiation and organ formation. To address these problems we use a combination of genomics, genetics, and molecular biology approaches in the model plant Arabidopsis thaliana, which is an outstanding model organism in which to dissect the connections between epigenetics and development. In a practical sense, our research program is relevant to understanding diseases, such as cancer, that result from the misregulation of genes and defects in the maintenance of cell identity. In addition, we hope to gain a deeper understanding of how plants build their bodies, which may ultimately help to guide crop plant engineering to improve important attributes.

Paul W. Doetsch, Ph.D. Biochemistry medpwd@emory.edu Faculty Website: http://www.biochem.emory.edu/labs/medpwd Molecular biology of DNA damage and repair. Major areas of research focus in this laboratory are (1) the biochemistry, molecular biology and genetics of DNA repair in eukaryotes and (2) the interaction of the transcriptional machinery with DNA damage. Our DNA repair studies include the characterization of the repair of oxidative and ionizing radiation-induced DNA base damage in the nucleus and mitochondria as well as the elucidation of a broad specificity alternative excision repair pathway. Studies on the effects of various types of DNA damage on RNA polymerases have led to our current investigations on the generation of mutant proteins via transcriptional bypass and miscoding at sites of damage (transcriptional mutagenesis) and the concept that this type of event has important biological consequences, particularly in non-dividing cells. In addition, a more recent area of interest is the connection between different DNA repair and damage processing pathways and the relationship to genomic instability.

Jin-Tang Dong, Ph.D. Oncology/Hematology and Urology j.dong@emory.edu Faculty Website: http://www.med.emory.edu/hemonc/faculty/basic_research/dong_jin-tang.html Molecular pathogenesis of human cancer - identifying genes mutated in cancer and dissecting their molecular pathways. The development and progression of cancer are driven by a series of mutations in a number of genes. The research in our laboratory involves both identifying novel cancer genes and studying how abnormalities of these genes cause cancer. For gene identification, we apply genetic and functional approaches to discover tumor suppressor genes located in chromosomal regions frequently deleted in human cancer. We have identified KLF5 from 13q21, FOXO1A from 13q14, ATBF1 from 16q22, and U50 from 6q15, but more genes remain to be discovered. We also identified WWP1 as an oncogene from 8q21, a chromosomal region often amplified in human cancer. The functions of these genes are being examined by tissue specific knockout or overexpression in mouse models and subsequent phenotypic and molecular analyses. Another important area of research is to dissect the molecular pathways involving these genes, especially KLF5 and ATBF1, by using biochemical approaches. We study how the signaling pathways are different between normal and cancer cells, and determine whether we can kill cancer cells by modulating the pathways. Such knowledge is useful for developing biomarkers in cancer detection and for therapeutic intervention in cancer treatment.

Michael P. Epstein, Ph.D. Human Genetics mpepste@emory.edu Faculty Website: http://genetics.emory.edu/faculty/faculty.php?facultyid=158 Statistical genetics and genetic epidemiology of complex human traits. I am primarily interested in the development of statistical methods for identifying genetic variants within humans that influence diseases and disease-related quantitative traits (e.g. blood pressure). My current research focuses on allele-based and haplotype-based statistical methods that identify genetic regions that are in linkage disequilibrium with disease. Additionally, I am involved in the development of flexible and powerful variance-component procedures for conducting linkage analyses of quantitative traits. My future research will explore the burgeoning area of high-dimensional genetic analyses. In particular, I am interested in the development of statistical methods for identifying large sets of genetic variants found throughout the human genome that collectively influence a quantitative trait of interest. In addition to developing such statistical methods, I am interested in applying them to real genetic studies of disease. Currently, I am involved in studies that seek to identify genetic variants that influence such disorders as PTSD, epilepsy, and diabetes.

Andrew P. Escayg, Ph.D Human Genetics aescayg@emory.edu Faculty Website: http://www.genetics.emory.edu/meet_our_team.php?faculty=escayg Understanding the molecular basis of common neurological disorders. Our lab uses a combination of human and mouse genetics, mouse disease models and genome analysis/bioinformatics in order to determine the molecular basis of inherited neurological disorders. We have a broad interest in neurological disease and the disorders that we are currently working on include epilepsy, ataxia and other movement disorders, and migraine. Of particular interest to us is the role of voltage-gated ion channels in disease. Voltage-gated ion channels play a critical role in neuronal signaling and the maintenance of normal nervous system function. Diseases that result from mutations in ion channel genes are called channelopathies. One component of our research involves the identification of families with inherited neurological disease. Once a suitable family is identified we begin the process of disease gene identification. To further understand disease mechanisms, we generate and study mice that carry the identified human mutations. We are also interested in understanding the genetic elements that regulate the expression levels of identified disease genes. This component of our research requires the use of bioinformatics, sequence analysis techniques, and cell culture.

Judith L. Fridovich-Keil, Ph.D. Human Genetics jfridov@emory.edu Faculty Website: http://genetics.emory.edu/faculty/faculty.php?facultyid=12 Roles of galactose and galactose metabolism in normal development, homeostasis, and disease. Galactose and its derivatives serve as essential components of glycoproteins and glycolipids in humans and other species. As a component of milk, galactose also serves as a key energy source for mammals, especially infants. Impaired metabolism of galactose leads to the potentially lethal disease classic galactosemia. We are applying a combination of basic and clinical approaches using patients, mammalian cells, flies, and microbial systems to explore the underlying bases of pathophysiology in galactosemia, and to define the roles of galactose and galactose metabolism in normal development and homeostasis. We are further working to develop novel and improved forms of intervention for patients with galactosemia

Andreas Fritz, Ph.D. Biology afritz@emory.edu Faculty Website: http://www.biology.emory.edu/index.cfm?faculty=28 Molecular and genetic mechanisms of the early patterning of the nervous system and segmentation of the mesoderm. Research in my lab mainly centers on the early development of sensory organs. We use zebrafish as a model system to investigate the induction and formation of the otic and olfactory placodes, which give rise to the inner ear and nose, respectively. Development of sensory placodes has been a long-standing model to address general, important concepts of developmental biology, such as induction, inherent cellular properties, fate specification and maintenance. We use genetic and molecular approaches to identify and characterize genes important in these processes.

Peng Jin, Ph.D. Human Genetics peng.jin@emory.edu Faculty Website: http://www.genetics.emory.edu/labs/jin/jin_lab_index.php Noncoding RNAs and Epigenetic Modulation in Neural Development and Brain Disorders. The importance of noncoding RNAs has been increasingly recognized within the last several years, particularly with the identification of new classes of small RNAs, such as microRNAs (miRNAs). These noncoding RNAs play important roles in neural development and can be involved in neuronal translation control (miRNAs) or transcription regulation (small modulatory RNAs in the fate specification of adult neural stem cells), and can be pathogenic (noncoding repeats in neurodegeneration). The ultimate goal of my lab is to understand the roles of noncoding RNAs in neural development and the pathogenesis of brain disorders. Currently we are focusing on several areas: 1) the role of microRNA pathways in learning and memory; 2) the molecular basis of RNA-mediated neurodegeneration; 3) small noncoding RNAs and epigenetic regulation; 4) chemical genomic approach to dissect small RNA pathway.

David Katz, Ph.D. Cell Biology djkatz@emory.edu Faculty Website: http://cellbio.emory.edu/lab/katz/katz.htm The study of histone modifications in the germline of C. elegans and mouse as a model for understanding basic stem cell biology and teh function of chromatin as an epigenetic transcriptional memory.

William G. Kelly, Ph.D. Biology bkelly@emory.edu Faculty Website: http://www.biology.emory.edu/research/Kelly/members/Bill.html Molecular Analysis of Epigenetic Regulation in Germ Cells We use the genetic model system C. elegans to study how the "mother of all stem cells", the germ line, is established during embryogenesis and maintained during development. We have identified an "epigenetic erasure" process that separates pluripotent germ cells from somatic cells in the early embryo, and are studying epigenetic mechanisms in the embryonic germline that guard the germ cells during early development and regulate genomic activation. We also study how chromatin-based silencing mechanisms are targeted to large genomic regions, particularly the X chromosome, in adult germ cells. We have discovered imprinted X inactivation in C. elegans, and are using this as a model to analyze how genetic imprinting is established in gametogenesis. We have also recently identified mechanisms that silence unpaired DNA during meiosis, and are investigating how such mechanisms contribute to genome stability.

Steven W. L'Hernault, Ph.D. Biology bioslh@emory.edu Faculty Website: http://www.biology.emory.edu/research/LHernault/members/Steve.html Spermatozoa must create a unique cell surface to participate in fertilization. My lab identifies and studies C. elegans mutants with defects in sperm surface assembly. C. elegans spermatozoa have secretory vesicles (MO) that fuse with and make the cell surface competent for fertilization. Many of our mutants affect MOs and we are determining how this organelle participates in cell surface assembly. Currently, we study several spe and fer genes required for MO function and/or cell surface assembly. The SPE-39 protein is required for MO biogenesis and it defines a new protein family required for vesicular trafficking, probably in all animals. The FER-1 protein facilitates MO fusion with the cell surface and its human homologs are implicated in muscular dystrophy and deafness. fer-14 and spe-42 are transmembrane proteins required for sperm-egg interaction during fertilization; the spe-42 gene has a mammalian homolog, of unknown function, expressed in testes. SPE-16 is an ubiquitin E3 ligase orthologous to Mind Bomb in vertebrates, where it negatively regulates Notch signaling. Mind Bomb is expressed during mouse spermatogenesis, but its role in this tissue is currently unknown. The spe-16 phenotype shows that Mind Bomb is required during spermatogenesis and we are currently determining its function.

Xiao-Jiang Li, Ph.D. Human Genetics xli2@emory.edu Faculty Website: http://www.genetics.emory.edu/FACULTY/faculty_bio_xli.php Molecular mechanism of Huntington's disease and neuronal function of huntingtin associated proteins. Research in my lab focuses on the pathogenesis of inherited neurodegenerative disorders that are caused by an expansion of a polyglutamine tract in the associated disease proteins. These disorders include Huntington disease and several spinal cerebellar ataxia diseases. It is unclear how mutant proteins with an expanded polyglutamine tract cause late-onset and selective neurodegeneration despite their widespread expression in the body and brain. To elucidate how polyglutamine expansion causes neuronal dysfunction and degeneration, we are studying animal and cell models of Huntington and polyglutamine diseases using a variety of molecular genetic and neurobiological approaches including transgenic mice, primary neuronal culture, protein purification, and electron microscopy.

John C. Lucchesi, Ph.D. Biology jclucch@emory.edu Faculty Website: http://www.biology.emory.edu/research/Lucchesi/ Regulation of transcription; functional architecture of chromatin. The goal of our laboratory is to contribute to the understanding of gene transcription. In cells, DNA is wrapped around nucleosomes; this association must be altered in order for the factors and enzymes responsible for gene activation and RNA synthesis to access promoter regions and for transcription to proceed. As a model system, we have been studying the mechanism of function of a regulatory multi-protein complex responsible for enhancing the transcriptional activity of a large number of genes on the X chromosome of Drosophila males. Our experimental goals are to determine how the complex recognizes the X chromosome and how it interacts with X-chromosome chromatin to affect gene transcription. Recently, we have discovered the presence of a closely related complex in humans.

Ichiro Matsumura, Ph.D. Biochemistry imatsum@emory.edu Faculty Website: http://www.biochem.emory.edu/labs/imatsum/ Directed evolution of novel protein function; experimental determination of the adaptive mechanisms. I would like to learn how proteins evolve new functions. A better understanding of adaptive molecular evolution will teach us how the complex machinery of life arose, and enable us to improve the human condition by engineering new nanoscale devices. We recapitulate the evolutionary process in our lab by randomly mutating genes that encode proteins and expressing libraries of mutants in populations of micro-organisms. We screen these populations for mutant proteins that exhibit some novel function, and randomly mutate the isolated clones for the next round of screening. After many iterations of random mutation and screening, we can isolate, sequence and characterize the evolved proteins. This enables us to learn how beneficial mutations improve function.

Ken Moberg, Ph.D. Cell Biology kmoberg@emory.edu Faculty Website: http://cellbio.emory.edu/lab/moberg/Home.html Our lab uses the fruit fly Drosophila melanogaster to study how the developmental control of apoptosis and proliferation restricts tissue size in vivo. Work in the lab is currently focused on three novel growth-inhibitory genes: archipelago, erupted, and gang of four. archipelago and gang of four function cell autonomously to restrict tissue growth, while erupted functions non-cell autonomously. We have cloned archipelago and erupted, and the mapping of gang of four is underway. We have shown that archipelago inhibits growth by degrading protein targets that include Cyclin E and dMyc, the fly ortholog of the human c-Myc cancer oncogene. Analysis of the function and regulation of archipelago and erupted using both genetic and biochemical techniques are ongoing.

Charles P. Moran, Jr., Ph.D. Microbiology & Immunology cmoran2@emory.edu Faculty Website: http://www.microbiology.emory.edu/moran_c.html Microbial genetics; gene expression during bacterial differentiation, RNA polymerase-promoter interactions. Research in my lab centers on the mechanisms that regulate gene expression and function during differentiation and development of bacterial endospores. These studies range from atomic level analyses of the mechanisms involved in promoter activation to microscopic studies of the assembly of subcellular structures.

Carlos S. Moreno, Ph.D. Pathology and Laboratory Medicine cmoreno@emory.edu Faculty Website: http://morenolab.whitehead.emory.edu/ Bioinformatics and DNA microarray analysis of tumors. Research in my wet lab focuses on application of DNA microarrays to understand the molecular mechanisms of cancer progression, the changes in gene expression that are essential for tumor formation, and identification of new therapeutic targets. In our computational research, we are developing novel bioinformatics and systems biology tools to integrate microarray and genomic data in an effort to reconstruct mammalian transcriptional networks.

Andrew S. Neish, M.D. Pathology and Laboratory Medicine aneish@emory.edu Faculty Website: http://pathology.emory.edu/AdminFacultyMember.cfm?Name_seq=244 Molecular events in the process of inflammation. Dr. Neish's research focuses on the interactions of bacterial pathogens with human epithelial cells in an effort to understand the molecular mechanisms of pathological and symbiotic relationships. Bacteria are thought to mediate interactions with eukaryotic cells by translocation of preformed "effector" proteins. Currently, we are interested in a family of prokaryotic effector proteins that we have shown have profound effects on host cellular signaling functions. The effects clearly involve immune signaling, and may also influence cellular survival, proliferation and development. The laboratory employs a variety of microbiologic, genetic, biochemical and cell biological techniques to approach this question, including use of mammalian cell culture, murine and Drosophila models and large-scale expression profiling using microarray technology.

John M. Nickerson, Ph.D. Opthalmology litjn@emory.edu Faculty Website: http://userwww.service.emory.edu/~litjn/ Retinal proteins and their expression in normal animals and in animal models exhibiting characteristics of human eye diseases. Whether as a treatment in human disease or as a laboratory tool, the delivery of nucleic acids into cells and expression of a gene is important. Many strategies have been proposed, and many to some degree, function as promised. Difficulties arise when migrating from a laboratory tool or proof-of-principle into a reasonable and effective therapeutic agent. Viruses and viral particles have been most effective so far, but they have drawbacks. Other approaches have not been as efficient. The invasiveness of current gene delivery schemes has been secondary to their efficiency and their associated risks such as immunogenicity. We are considering noninvasive technologies to circumvent many problems with present gene delivery approaches. We employ mouse models of human ocular genetic diseases in testing gene delivery.

Grace Pavlath, Ph.D. Pharmacology gpavlat@emory.edu Faculty Website: http://www.pharm.emory.edu/gpavlath/index.html Mouse genetic models of muscle stem cell biology and muscular dystrophy. Skeletal muscle is one of the few tissues in the body that is highly regenerative due to the presence of stem cells. Therefore, it serves as an excellent model for studying tissue repair and stem cell biology. Multiple genetic diseases affect the ability of skeletal muscles to regenerate leading to loss of muscle mass, which is detrimental to health. We employ in vitro techniques as well as mouse genetic models to identify the molecules and signal transduction pathways that control different aspects of muscle stem cell behavior such as proliferation, migration, adhesion and fusion. In addition, we study how mutations in the ubiquitous nuclear RNA binding protein, PABP1, lead to oculopharyngeal muscular dystrophy (OPMD), a disease that specifically affects muscles of the eye and pharynx (swallowing muscles). We have created several unique mouse models in order to understand why this disease specifically targets skeletal muscle and not other tissues.

Daniel Reines, Ph.D. Biochemistry dreines@emory.edu Faculty Website: http://www.biochem.emory.edu/cgi-bin/people/detail_faculty?id=dreines Biochemistry and molecular genetics of RNA polymerase II transcription. The first of two projects examining the biochemistry and molecular genetics of RNA polymerase II transcription is a study of FMR1 transcription. We have characterized this transcriptionally silenced and heterochromatinized gene in terms of histone modification, DNA methylation, and loss of transcription factor binding. We are designing efforts to reactivate it using a variety of approaches. The second project is an analysis of transcription mechanisms using S. cerevisiae. Regulation of genes dependent upon elongation factors is being studied using genetics and biochemistry including genes involved in nucleotide metabolism. IMD2 transcription is induced with drugs that target this pathway and are used in patients as immunosuppressants. We can now observe inhibition of Imd2p in treated cells which should be therapeutically important.

Katie Rudd, Ph.D. Human Genetics katie.rudd@emory.edu Faculty Website: http://genetics.emory.edu/faculty/faculty.php?facultyid=539 Mechanisms of subtelomeric breaks. Genomic changes at the ends of chromosomes are a major source of human diversity and disease. We are interested in the structure and function of subtelomeres: regions at the ends of chromosomes adjacent to telomere repeats. Subtelomeres are a particularly dynamic part of the human genome, subject to rampant double-strand breaks (DSBs) and DNA transfers. The Rudd lab investigates the mechanism of breakage at chromosome ends, in search of DNA sequence motifs that promote genomic instability.

Harold I. Saavedra, Ph.D. Radiation Oncology hsaaved@emory.edu Faculty Website: http://www.emoryradiationoncology.org/switch.cfm?action=BOBIO&BOID=5 How loss of tumor suppressors and activation of oncogenes signaling through the CDK/RB/E2F pathway result in centrosome amplification, genomic instability and mammary tumors. Our working hypothesis is that oncogenes and loss of tumor suppressor activities initiate cancers by inducing centrosome amplification, aneuploidy and genomic instability. To test this hypothesis, we use a series of transgenic mice and various conventional and conditional knockout mice. The GFP-centrin-2 transgenic mice will be used as a marker to explore whether loss of p53 and E2F3, known suppressors of centrosome amplification, results in centrosome amplification in vivo, and whether inducible expression of Ras and Myc in mammary glands results in increases in centrosome amplification that precede mammary cancers. We will explore whether loss of tumor suppressors or activation of oncogenes induce centrosome amplification and tumorigenesis via the CDK/Rb/E2F pathway. The ultimate goal of our lab is to identify common targets that are unregulated by oncogenic and tumor suppressor pathways and that are critical to centrosome amplification and mammary tumorigenesis.

Subhabrata Sanyal, Ph.D. Cell Biology ssanya2@emory.edu Faculty Website: http://userwww.service.emory.edu/~ssanya2/ The primary goal of my laboratory is to study genetic determinants of learning and memory. We use Drosophila as a model system to investigate signaling networks that operate in neurons to modulate both pre - and post-synaptic plasticity. Enduring modifications in neuronal connectivity require synthesis of new proteins either through transciption. We have establish that conserverd signaling cascades such as those mediated by cAMP, PKA and MAPK operate in our model system to cause long-term change. These signaling cascades finally impinge on transcription factors to drive expression of "plasticity genes". Among several broad questions in the field that interest us are studying signaling cross-talk during plasticity and the identification and functional validation of target genes. Our overall aim is to ascertain how transcription factor networks are utilized in intact orgaisms, thus uncovering conserved [rinciples of learning across species.

Iain T. Shepherd, Ph.D. Biology ishephe@emory.edu Faculty Website: http://www.emory.edu/BIOLOGY/ishephe/ Molecular and genetic mechanisms in enteric nervous system development, using zebrafish. My lab studies the genetic basis of the development of the enteric nervous system (ENS) using the zebrafish model system. The ENS is the largest most complicated subdivision of the peripheral nervous system and is completely derived from neural crest stem cells (NCSC). The lab is interested in determining what genes are involved in the specification of the NCSC that form the ENS. We are also interested in determining what molecules are involved patterning the migration of NCSC in the intestine. We use genetic, cell biological and embryological experimental techniques in our studies. These studies are clinically important. Hirschsprung's disease is a pediatric ENS condition that affects 1 in 5000 live births the cause of which is only partly understood.

Stephanie L. Sherman, Ph.D. Human Genetics ssherma@emory.edu Faculty Website: http://genetics.emory.edu/faculty/faculty.php?facultyid=21 Genetic epidemiology of complex human disorders including chromosome nondisjunction and Fragile X Syndrome. Our research focuses on defining the variation in outcome of two syndromes and their related phenotypes: 1) Down syndrome (DS) and associated birth defects and 2) fragile X syndrome (FXS) and other gene related phenotypes (premature ovarian failure (POF) and tremor/ataxia syndrome (FXTAS)). For each, we use genetic epidemiological approaches ask specific questions identify genetic and environmental risk factors that increase susceptibility for each trait. Specifically for DS, we combine cytogenetic, molecular and epidemiological tools to examine the maternal age effect that increases the risk for chromosome nondisjunction. We also study genetic risk factors for DS-associated congenital heart defects. For FXS, we have a large study to understand the neuropsychological, neurological and reproductive profile of individuals who carry specific forms of the fragile X mutation.

Alicia K. Smith, Ph.D. Psychiatry and Behavioral Sciences aksmith3@emory.edu Faculty Website: hhttp://behavioralgenetics.net/ Research in this laboratory focuses on the molecular genetics of complex behavioral and clinical traits related to psychopathology. We utilize a number of complementary approaches, including genome-wide methods, to explore the potential genetic and epigenetic contributions to childhood and adult psychiatric problems. These studies incorporate examinations of DNA methylation patterns, mRNA expression, pharmacogenetics, and gene-environment interactions.

Erwin G. Van Meir, Ph.D. Neurosurgery, Hematology/Oncology and Winship Cancer Institute evanmei@emory.edu Faculty Website: http://neurosurgery.emory.edu/FacultyVanMeir.htm Dr. Van Meir's research interests lie in understanding the molecular basis for human brain tumor development and how we can use this knowledge to devise new therapeutics that will improve patient survival. We examine how genetic alterations and hypoxia induce changes in cell biology that promote tumor formation with particular emphasis on tumor angiogenesis. We also develop novel therapeutic approaches for cancer using oncolytic adenoviruses and anti-angiogenic molecules including small molecule inhibitors of the hypoxia-inducible factor pathway.

Paula M. Vertino, Ph.D. Radiation Oncology at Winship Cancer Institute pvertin@emory.edu Faculty Website: http://www.emoryradiationoncology.org/dcb/vertino/vertinolabpeople.html DNA methylation and epigenetic mechanisms of human carcinogenesis. Aberrant gene silencing resulting from alterations in DNA methylation and chromatin structure play an important role in the inactivation of tumor suppressor and other genes in human cancers. My laboratory uses a number of approaches ranging from the detailed molecular analyses of individual genes, to cell biology and functional genomics, to investigate the molecular mechanisms underlying these gene silencing events, and to study how the epigenetic silencing of certain genes contributes to human carcinogenesis.

Ya Wang, Ph.D. Radiation Oncology at Winship Cancer Institute ywang94@emory.edu Faculty Website: http://www.emoryradiationoncology.org/switch.cfm?action=BOBIO&BOID=4 Dr. Ya Wang’s research focuses on the study of how mammalian cells respond to DNA double strands break (DSB). Because DNA is the main target of radiation and DNA DSB is the most severe threat for cell survival and genomic integrity, studying the mechanism by which mammalian cells respond to DNA DSB is not only a key issue for improving radiotherapy of cancer patients but also a key issue for preventing carcinogenesis. Her on-going projects are divided into two categories: (1) Study how to sensitize tumor cells to radiation-induced DNA DSB and, subsequently provide useful information for improving radiotherapy; (2) Study how radiation-induced DNA DSBs initiate carcinogenesis and, subsequently provide useful information for improving cancer prevention. For the first category, there are two projects: (i) study how the ubiquitine-mediated degradation of CHK1 affects the cell response to DNA DSBs. (ii) To study how to use miRNAs as an approach to target radiation-induced genes and sensitize tumor cells to radiotherapy. For the second category, there is one project: To study how miRNAs through their targets affect different types of radiation (low linear energy transfer (LET) and high-LET radiation)-induced carcinogenesis. Dr. Wang’s lab is using molecular biology, cellular biology and transgenic mouse models to accomplish these projects.

Stephen T. Warren, Ph.D. Human Genetics swarren@emory.edu Faculty Website: http://www.genetics.emory.edu/labs/warren/warren_lab_index.php Our research is directed toward understanding the mechanisms of human diseases. A large component of the research program involves fragile X syndrome, a common cause of mental retardation and autism that is due to a trinucleotide repeat expansion in the FMR1 gene. The research is multifaceted and broad in approach. We work with patients as well as with model systems (mouse, fly, annnd cell culture) to understand the pathophysiology of the disorder. For example, biochemical and neurobiological studies are directed at understanding the consequence of the loss of FMR1 expression on local protein synthesis (the normal function of the encoded protein) in neuronal dendrites. Drosophila and mouse studies are aimed at discovering and evaluating potential drugs that may abrogate the loss of FMR1 function. Large-scale resequencing of FMR1 in patients is being undertaken to uncover conventional mutations and examine genotype/phenotype correlations. High-throughput diagnostics have been devloped for ongoing prevalence studies in 100,000 newborns. Other studies involve genome-wide analysis of copy number variation in humans as normal polymorphisms as well as pathological variants influencing schizophrenia or cognitive deficiencies.

Barry Yedvobnick, Ph.D. Biology byedvob@emory.edu Faculty Website: http://www.biology.emory.edu/index.cfm?faculty=48 The Notch pathway is a major signaling system within metazoa, functioning in a range of developmental and disease-related processes. Despite intensive analysis, Notch signaling is not well understood, and it appears that additional pathway components need to be identified and characterized. Using genetic and molecular methods, our lab is screening for loci that may be implicated in Notch signaling.

Shozo Yokoyama, Ph.D. Biology syokoya@emory.edu Faculty Website: http://www.emory.edu/BIOLOGY/syokoya/main.html The long-term goal of our research is to elucidate the molecular genetics and evolution of color vision in vertebrates. We are currently working on five major areas: 1) the molecular genetics and evolution of UV vision; 2) adaptive evolution color vision of deep-sea fishes; 3) physical chemistry of color vision (collaboration with Dr. Keiji Morokuma, Emory Univ.); 4) X-ray crystal analyses of color vision (with Dr. Hideaki Moriyama, Univ. of Nebraska); and 5) functional genomics of eyed river fishes (Astyanax fasciatus) and their blind forms from different Mexican caves (with Dr. Takashi Gojobori, National Institute of Genetics, Japan and Dr. Bill Jeffereys, University of Maryland).

David S. Yu, M.D., Ph.D. Radiation Oncology dsyu@emory.edu Faculty Website: http://www.emoryradiationoncology.org/switch.cfm?action=MDBIO&MDID=14 The precise replication of the genome and the continuous surveillance of its integrity are essential for cell survival and the avoidance of various diseases, including aging, neurodegeneration, and cancer. We are interested in understanding how cells respond to replication stress and how we can utilize this knowledge for improvements in cancer diagnosis and treatment. One interest of the lab is to identify novel components of the replication stress response, which mediate sensitivity of cancer cells to DNA damaging agents, utilizing high throughput loss of function genetic screens. A second interest of the lab is to understand mechanistically how these novel replication stress response proteins function using molecular, genetic, and biochemical approaches to define the functions of these proteins. A recent interest of our lab is to understand the role of sirtuin deacetylases in orchestrating the replication stress response. Finally, we are interested in translating insights gained from our mechanistic analyses to improvements in the clinic. By exploiting defects in the replication stress response, we hope to utilize novel replication stress response proteins as biomarkers for clinical response and outcome to specific cancer treatments and as novel therapeutic targets to personalize cancer therapy.

Wei Zhou, Ph.D. Oncology and Hematology wzhou2@emory.edu Faculty Website: http://www.winshipcancerinstitute.org/extra/labs/zhou/ The tumor genome is a dynamic, unstable entity and constantly undergoes changes due to genomic instability. Among the numerous genetic alterations in tumor cells, only a few events lead to the activation of oncogenes or the inactivation of tumor suppressor genes, both of which are essential for tumor development. Most genetic alterations in tumors are passenger mutations, and one of the greatest challenges in the field of cancer genetics is the identification of those specific mutations that spur tumorigenesis. We have previously combined the use of epidemiology, genome-wide gene expression analyses, and molecular genetics to identify Sox7 as a tumor suppressor on the short arm of chromosome 8p, and we are currently investigating the role of Sox7 in the development of prostate cancer. In addition, we are also studing in the role of LKB1 tumor suppressor gene in the formation of non-small cell lung cancer.

Assem G. Ziady, Ph.D. Pediatrics aziady@emory.edu Faculty Website: http://www.pedsresearch.org/research-faculty/profile/assem-ziady The Ziady lab research is diversified into two fields of research, redox mediated inflammatory signaling and design and application of non-viral gene delivery vectors. The lab has expertise in proteomics, biochemical analyses of antioxidant enzyme function, analyses of protein expression and modification, small animal imaging, the design of mammalian expression cassettes, and the design of gene delivery vectors. The lab also uses state of the art software to study and analyze cellular pathways in conjunction with our proteomic studies using our dedicated LC mass spectrometer to gain insight into the systems biology of inflammatory lung disease, particularly for cystic fibrosis (CF). In addition to pursuing the use of DNA nanoparticles (3 patents held) for gene therapy in the lung, brain, and liver, the lab also studies the role of the antioxidant response element (ARE) in inflammatory signaling by CF airway epithelial cells. We discovered that Nrf2, a transcription factor central to ARE, is downregulated in CF cells and we were the first to describe a decrease of Nrf2 function in CF epithelia and show that this resulted in a significant increase in oxidants that stimulate inflammation. More recently the lab has described the mechanism of downregulation of Nrf2, which stems from feedback responses to the loss of CFTR function.

Michael Zwick, Ph.D. Human Genetics mzwick@emory.edu Faculty Website: http://genetics.emory.edu/faculty/faculty.php?facultyid=411 Our research uses the latest genome-wide genotyping and next-generation DNA sequencing platforms in order to make genomic variation detection rapid and inexpensive. The three main avenues of research in our laboratory include: - Developing open source software tools that speed the planning, implementation, analysis and interpretation of genome-wide datasets - Conducting studies whose goals include identifying genetic variants contributing to autism susceptibility, with a special emphasis on variants located on the human X chromosome. - Characterizing the role of copy number variants (CNVs) as causative factors in atrio-ventricular septal defects in children with Down Syndrome. In all of our studies, our ultimate goal is to understand how variation in the genome contributes to variation in important phenotypes in human and model systems.

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