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    Pathology & Laboratory Medicine
    Emory University School of Medicine
    Emory University Hospital
    Room H183
    1364 Clifton Road, NE
    Atlanta, GA 30322, USA

    Primary Areas of Research:

  • Bioinformatics
  • Cancer Biology
  • Cardiovascular Research
  • Epithelial Cell Biology
  • HIV/SIV
  • Immunology
  • Infectious Diseases
  • Oncology/DNA Repair
  • Renal Pathology
  • Signal Transduction
  • Transfusion Medicine
  • Core Facilities - Resources:

    ·  WCI-Pathology Core Lab

    Pathology Research Student

    Experimental Pathology Division

    Charles A. Parkos, MD, PhD, Director

    As the discipline dedicated to understanding human diseases, Pathology has deep roots in research. All of the diagnostic methods that pathologists now use routinely for patient care - including monoclonal antibodies, electron microscopy, DNA sequencing, flow cytometry, and in situ hybridization - were once breakthrough technologies found only in research laboratories at the cutting edge of biology. At Emory, our Pathology Department continues in this tradition of advancing health through basic research and through continually applying the newest knowledge and technologies in order to find better ways of diagnosing, preventing, and treating disease. With more than forty faculty investigators, state-of-the-art facilities, and over $55 million in annual research funding, we rank among the top 3 pathology departments in NIH grant funding, and are at the forefront of research and discovery in a wide range of fields. The medicine of tomorrow is in Pathology's research laboratories today.

    Experimental Pathology at Emory covers the spectrum from basic cellular and molecular processes through applied disease research. In addition to our longstanding strengths in immunology and molecular oncology, our Department has built renowned programs in HIV-AIDS, epithelial biology, neuroscience, and microbial pathogenesis. Our close partnerships with the nearby Centers of Disease Control (CDC), Yerkes National Primate Center, Georgia Institute of Techology, and others offer unparalleled resources and opportunities for research. Within our highly interactive Department, basic scientists have a unique opportunity to work side-by-side with their clinician colleagues and to see their discoveries applied rapidly in patient care.

    As part of our commitment to discovery, Emory Pathology offers numerous opportunities for training in biomedical research. Intensive research training with Pathology faculty is available through postdoctoral fellowships or through Emory's outstanding interdisciplinary graduate programs. We offer a specialized research track for residents who already have a strong background and commitment to an investigative career, and we proudly support our many other interested residents or clinical fellows who participate in basic, clinical, or translational research projects during clinical training, and so make their own unique contributions to scientific discovery and biomedical research. Our Department also strongly supports and encourages clinical residents and fellows who are interested in pursuing laboratory research as part of their training, and who will take their place among the next generation of leaders in disease research.

    Meet our Experimental Pathology faculty...


    Pathology Faculty Photo

    Susan A Allen, MD, MPH


    Professor
    Vaccines


    Research Interests -

    HIV Research - I have been working with HIV in Africa since the first recognition of the epidemic on that continent in 1985. My initial work was focused on the epidemiology, natural history, and manifestations of HIV infection in African men and women. Building on previous work, this grew to include collaborative studies of the virologic, immunologic, and immunogenetic correlates of transmission from men to women and women to men. In addition to the observational studies, I have also worked on development and testing of HIV prevention strategies including behavioral (couples; HIV testing, combined prevention of HIV and unplanned pregnancy) and biomedical interventions (HIV vaccine candidates, vaginal microbicides, acyclovir). Recently, I have added a translational aspect to the work, with an emphasis on implementation of evidence-based prevention programs in the public health sector.


    Pathology Faculty Photo

    Aftab Ahmed Ansari, PhD


    Professor
    Immunology
    HIV/SIV Pathogenesis
    Vaccines


    Research Interests -

    Mechanisms of disease resistance in SIV infected sooty mangabeys - The sooty mangabeys is a species of monkeys which is naturally infected with the simian immunodeficiency virus ( SIV ) but remains completely healthy throughout its life. SIV isolated from this species when used to experimentally infect rhesus macaques develop chronic debilitating disease similar to human HIV infected individuals. My lab has shown that this 2 distinct clinical outcomes is not secondary to viral loads, the cell lineages that become infected in these 2 species and while both the disease resistant and susceptible species develop reasonable titers of SIV specific antibodies, only the disease susceptible species develops virus specific cellular responses.This finding is indeed a paradox. My lab is now focused on using antibodies and chemotherapeutic agents which deplete specific cell lineages in vivo in effort to identify the importance of each of these cell lineages in disease resistance and susceptibility.

    Mechanism of pathogenesis of human primary biliary cirrhosis - Autoimmune mechanisms have been implicated in the pathogenesis of human PBC. The major autoantigens for human PBC have been cloned , sequenced and the immunodominant T and B cell epitopes identified. My lab has been involved with identifying a role for the lipoate molecule which is associated with the lysine residues of each of the immunodominant peptides. We believe that the lipoate molecule serves as a hapten and environmental pollutants serve as chemical mimics replace the lipoate molecule which is sufficiently different to break tolerance and initiate the autoimmune process. Studies aimed at proving this hypothesis are the focus of the lab.


    Pathology Faculty Photo

    Guy M Benian, MD


    Professor
    Muscle Cell Biology


    Research Interests -

    - The sarcomere performs the work of muscle contraction and is a "nano"-machine consisting of a highly ordered assemblage of several hundred proteins. Despite ever increasing knowledge of the components and functions of sarcomeric proteins (indeed new ones are discovered each year!), we still dont understand how sarcomeres are assembled, and maintained in the face of muscle contraction. Our lab is studying these questions in the model genetic organism, C. elegans. C. elegans is a superb platform for discovery of new and conserved sarcomeric components, and for learning new information about already known components. We are focused 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? Our approaches involve genetics, cell biology and biochemistry. Our studies benefit from collaborations with structural biologists, biophysicists and biomedical engineers. Our studies have relevance for understanding the molecular mechanisms of human inherited diseases of skeletal and heart muscle, including muscular dystrophies, myopathies and cardiomyopathies. 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. In C. elegans, there are 3 such proteins, twitchin (754,000 Da, located in the sarcomeric A-band, and one function likely to be regulation of muscle relaxation), TTN-1 (2.2 MDa, located in the I-band and Read more...


    Pathology Faculty Photo

    Daniel J Brat, MD, PhD


    Professor
    Cancer Biology
    Neuropathology


    Research Interests -

    Mechanisms Underlying Glioblastoma Progression - We investigate mechanisms of progression to glioblastoma (GBM), the highest grade astrocytoma, including genetics, hypoxia, and angiogenesis. Progression is characterized by tumor necrosis, severe hypoxia and microvascular hyperplasia, a type of angiogenesis. We propose that vaso-occlusion and intravascular thrombosis within a high grade glioma results in hypoxia, necrosis and hypoxia-induced microvascular hyperplasia in the tumor periphery, leading to neoplastic expansion outward. Since the pro-thrombotic protein tissue factor is upregulated in gliomas, we investigate mechanisms of increased expression and pro-coagulant effects.

    In Silico Brain Tumor Research - We initiated an In Silico Center for Brain Tumor Research to investigate the molecular correlates of pathologic, radiologic and clinical features of gliomas using pre-existing databases, including as TCGA and Rembrandt. Using datasets and image analysis algorithms, we study whether elements of the tumor micro-environment, such as tumor necrosis, angiogenesis, inflammatory infiltrates and thrombosis, may correlate with gene expression subtypes in TCGA gliomas. We also have demonstrated the clinical relevance of TCGA subclasses within the lower grade gliomas using the Rembrandt dataset.

    Regulators of Asymmetric Cellular Division in Glioblastoma Stem Cells - We study mechanisms that confer specialized biologic properties to glioma stem cells (GSC) in GBM. The Drosophila brain tumor (brat) gene normally regulates asymmetric cellular division and neural progenitor differentiation in the CNS of flies and, when mutated, leads to a massive brain containing only neuroblastic cells with tumor-like properties. We study the human homolog of Drosophila brat, Trim3, for its role in regulating asymmetric cell division and stem-like properties in GSCs. Trim3 may elicit its effects is through repression of c-Myc.


    Pathology Faculty Photo

    Max Dale Cooper, MD


    Professor
    Immunology


    Research Interests -

    - My laboratory pursues ontogenetic and phylogenetic studies of the adaptive immune system in parallel with the analysis of immunological diseases in humans. Current projects include the role of immunoglobulin and non-immunoglobulin genes in B cell development, and the evolution of adaptive immune systems in vertebrates.


    Pathology Faculty Photo

    Cynthia Ann Derdeyn, PhD


    Associate Professor
    HIV Pathogenesis
    Vaccines


    Research Interests -

    HIV/AIDS - The extraordinary genetic diversity of global human immunodeficiency virus type 1 (HIV-1) strains, especially within the envelope (Env) glycoproteins, is a force to be reckoned with regards to vaccine design. However most current strategies simply ignore this problem by focusing on one or a few viral strains. It has also become painfully clear that vaccines designed to elicit cell-mediated immunity without an antibody-inducing component are not protective or beneficial, bringing the conundrum of how to elicit broadly protective neutralizing antibodies against HIV-1 Env back into the forefront. In our research, we have continued to focus on individuals in Africa that are infected with the globally predominant HIV-1 subtypes, such as A and C. We have recently begun to uncover differences between the HIV-1 subtypes within the Env glycoproteins, which are highly variable in sequence and are the major targets for neutralizing antibodies. These differences have the potential to impact the selection and design of vaccine immunogens. Our major approach is to determine how subtype C HIV-1 is neutralized by autologous antibodies in Zambian individuals, and how the virus subsequently escapes, in the context of the viral diversity in which these processes occur. Remarkably, these processes remain poorly understood. We do this by analyzing in detail samples collected longitudinally from newly infected individuals in Zambia, from acute/early infection into the chronic phase, to understand how the hyper-variable and structural domains of the Env glycoproteins evolve as the immune resp Read more...


    Pathology Faculty Photo

    Marla Gearing, PhD


    Assistant Professor
    Neuropathology


    Research Interests -

    The overlap among neurodegenerative diseases, particularly Alzheimer's disease and Parkinson's disease - There is considerable clinical and neuropathologic overlap among neurodegenerative diseases. Lewy bodies are frequently found in the brains of patients with Alzheimer's disease, and Parkinson's disease patients frequently show Alzheimer's disease at autopsy in addition to their Parkinson's disease. In addition, there in considerable clinical and neuropathologic heterogeneity and overlap in the family of diseases known as "tauopathies". We are interested in the pathogenetic mechanisms underlying these diseases and in how these mechanisms interact with one another.

    Regional differences in amyloid deposition, processing and association with apolipoprotein E - While the neocortex displays both neuritic and diffuse plaques in Alzheimer's disease, plaques in the the striatum and cerebellum are predominantly, if not exclusively diffuse, regardless of disease duration. Furthermore, ApoE colocalizes with a subset of plaques in the neocortex and cerebellum, but not in the striatum. Neurofibrillary pathology in the neocortex is typically abundant in throughout much of the neocortex, but the occipital cortex is often relatively, if not entirely, spared. Such regional differences are not only intriguing, but an understanding of the factors underlying these differences could shed light on the pathogenesis of Alzheimer's disease.


    Pathology Faculty Photo

    Eric Hunter, PhD


    Professor
    HIV Pathogenesis
    Vaccines


    Research Interests -

    Molecular Biology of HIV and other Retroviruses - Research in my laboratory centers on the replication and pathogenesis of retroviruses, with a particular focus on the development of novel therapeutic and vaccine approaches to HIV. Using a model system based on the primate retrovirus Mason-Pfizer monkey virus (M-PMV), we are studying the viral-host interactions that are necessary for assembly of virions. These studies have identified unique insights into the mechanisms the virus employs for intracellular targeting of components necessary for the assembly and release of infectious virions.

    HIV-1 Glycoprotein-mediated Entry - Over the past several years, our laboratory has characterized the biosynthesis and transport of the HIV-1 glycoprotein (Env), and has identified protein domains critical for fusion and entry of the virus. Our current studies focus on the membrane-spanning component of the Env complex, gp41, which not only acts as the membrane fusion machine for the virus, but also targets Env to the site of virus assembly. These studies utilize molecular genetics approaches to dissect out structure-function relationships within the protein, with the goal of identifying new therapeutic targets for HIV-1.

    Heterosexual Transmission of HIV-1 - Employing knowledge and technology gained in the molecular characterization of the HIV Env complex and its role in membrane fusion, we have embarked on studies in Rwanda and Zambia aimed at defining, at a molecular level, the nature of the virus that establishes infection following heterosexual transmission. Studies from more than 20 transmission pairs show that a severe genetic bottleneck occurs during transmission, with a single genetic variant initiating infection in the new host. Studies are ongoing to define the unique biological and structural properties of the transmitted virus with the goal of targeting these variants with vaccines. We are also investigating how HIV-1 adapts over time to cellular and humoral immune pressures as it is transmitted from one immunogenetic environment to another. These studies will provide keys to the mechanisms HIV uses to evade the immune response of a newly infected host.


    Pathology Faculty Photo

    David L Jaye, MD


    Assistant Professor
    Hematopathology
    Cancer Biology


    Research Interests -

    Inflammation/ Hematopathology - I have 2 areas of ongoing investigation. One focus is a C-type lectin-family receptor (CD303) expressed uniquely on the surface of human plasmacytoid dendritic cells. Data suggest that this receptor impacts function of these cells in innate and adaptive immunity. We have developed unique biochemical tools to better understand the structure and function of CD303 including identification of natural binding targets whether of self or non-self origin. Specific efforts focus on identifying the specific counter-receptors on these targets and better characterizing the impact of receptor-ligand engagement. A second focus involves deciphering the role of the Bcl-6 interacting transcriptional co-repressor MTA3 and BCL6 in B cell lymphomas, work done in collaboration with Dr. P. Wade at NIEHS, and translating this knowledge into diagnostically useful tools.


    Pathology Faculty Photo

    Daniel Kalman, PhD


    Associate Professor
    Microbial Pathogenesis


    Research Interests -

    How bacterial and viral pathogens interface with the host - The general goal of my laboratory is to understand how bacterial and viral pathogens interface with the host. We have focused on two mechanistic aspects of this interface: (i) the immunological detection and clearance of the infection, and (ii) host systems utilized by the pathogen to facilitate infection. Our work has focused on two pathogens: enteropathogenic E.coli (and the related enterohemmorhagic E. coli, the cause of "raw hamburger disease), and vaccinia virus (a relative of variola virus, the cause of smallpox). We have utilized a combination of experimental approaches including cell biology assays based on high resolution deconvolution microscopy, biochemical systems that permit reconstitution of cellular responses with cytoplasmic extracts in permeablized cells, mouse genetic systems that model human disease, and permit investigation of the immunological response to the pathogen, and a C. elegans model system which allows genetic dissection of both host and pathogen. A long-term goal of the laboratory is to develop approaches that will permit identification of agents useful in treating disease. There is considerable impetus for developing such agents to treat infections caused by bacterial and viral pathogens: development of resistance to antibiotic or other chemotherapies looms as perhaps the single most important public health concern confronting humans in the coming century. In this regard, our current efforts have led to the development and testing of novel inhibitors of pathogenic E.coli infections, which interfere with the interface Read more...


    Pathology Faculty Photo

    J. David Lambeth, MD, PhD


    Professor
    Cancer Biology
    Cardiovascular Biology


    Research Interests -

    Reactive Oxygen Species (ROS) - Studies focus on reactive oxygen species (ROS) such as superoxide and hydrogen peroxide, and their biological roles, for example, in innate immunity, mitogenic growth, apoptosis, angiogenesis, and biosynthesis/ remodelling of extracellualr matrix. Starting in 1999, we described a new family of ROS-generating enzymes, the Nox/Duox family. This group of enzymes catalyzes the regulated generation of superoxide in response to signals including hormones, growth factors and immune mediators. The enzymology and regulation of ROS generation by the Nox enzymes and their regulatory proteins is an active area of investigation in our group. The biological function of these enzymes is being investigate in various model systems including cell culture, Drosophila melanogaster, C. elegans and mouse. In addition, the function of these enzymes in pathological conditions including cancer and atherosclerosis, and in normal aging is under active investigation. These enzymes now provide novel targets for development of anti-cancer and anti-arteriosclerotic drugs, which are currently under development by our group. These are predicted to be useful in the treatment and prevention of hypertension, atherosclerosis, and certain forms of cancer. The laboratory uses multi-disciplinary approaches ranging from enzymology and biochemistry to cell biology to animal models.


    Pathology Faculty Photo

    William Lewis, MD


    Professor
    Cardiovascular Biology
    HIV Pathogenesis
    Cardiac Pathology


    Research Interests -

    Mitochondrial DNA replication in disease: AIDS, congestive heart failure, hepatitis, renal failure - One classic biological teaching is that mitochondria are the "powerhouses of the cell", particularly in tissues that require significant energy, like heart, liver and muscle. The focus of the Lewis lab is the diverse effects of toxins on mitochondria structure and function. The primary focus is the untoward mitochondrial effects of a class of drugs called nucleoside reverse transcriptase inhibitors (NRTI) used to treat HIV infection, that are known to inhibit mitochondrial (mt-) DNA replication in vitro. These drugs are toxic to various tissues including heart, skeletal muscle, liver and kidney. Our overall goals are to (1) define the molecular mechanisms of how NRTIs change the abundance of precursors for mtDNA replication in vivo (2) define the effects of active NRTI triphosphates on the mitochondrial replicon in vivo (3) define the effects of specific polymerase mutants on the replication of mtDNA in vivo and (4) define the effects of the mtDNA template itself on its replication in vivo. The approach taken employs tissue specific targeting of genes involved in the processes and evaluation of structural and functional defects that result using state of the art biochemical, molecular, physiological, and pathological approaches. Conditional, tissue specific targeting also is addressed. The direct clinical benefits of these studies are twofold (1) the toxicity of important compounds is defined so that better therapeutics can be designed and administered and (2) mechanisms of organ specific changes in HIV disease and related illnesses are elucidated.


    Pathology Faculty Photo

    Carlos Sanchez Moreno, PhD


    Associate Professor
    Cancer Biology
    Bioinformatics


    Research Interests -

    Bioinformatics tools for identification of important cis-regulatory DNA elements - My laboratory is using DNA microarrays to identify novel targets for cancer therapies and developing bioinformatics tools to integrate microarray and genomic data to enable identification of important cis-regulatory DNA elements. We are analyzing expression patterns from both in vitro and in vivo mouse models to attempt to understand the changes in gene expression that are essential for tumor formation. Our analyses of human prostate carcinomas have identified developmental transcription factors that are highly correlated with Gleason score (or tumor grade) and may confer a stem-cell like phenotype to prostate cancer cells. We are focusing on identifying the downstream targets of these transcription factors, the developmental pathways that they are affecting, and why these factors are overexpressed in cancers. We are also investigating their potential as therapeutic targets using in vivo small-interfering RNA (siRNA) approaches. Finally, we are using our bioinformatics tools to analyze the regulatory elements of all human genes with the ultimate goal of building comprehensive models of gene networks in mammalian cells and understanding how those networks are disrupted in cancers.


    Pathology Faculty Photo

    Andrew Scott Neish, MD


    Professor
    Epithelial Pathobiology
    Immunology
    Microbial Pathogenesis


    Research Interests -

    Host-microbe interactions - Host-microbe interactions: Our laboratory studies innate immunity and epithelial biology relevant to normal intestinal physiology as well as infectious (Gram negative enterocolitis), idiopathic (idiopathic inflammatory bowel disease) and developmental (necrotizing enterocolitis) inflammatory disorders of the gut. Specifically, our research program investigates the interactions of enteric pathogens and members of the normal gut microbiota and their products with epithelial cells in an effort to understand the molecular mechanisms of pathological and commensal eukaryotic-prokaryotic relationships. Eukaryotic cells recognize bacteria via surface receptors (pattern recognition receptors) that bind conserved microbial structural motifs. This includes the formyl peptide receptors, which can mediate both inflammatory and non inflammatory signaling, and potentially play key roles in normal intestinal homeostasis and response to infection. These receptors induce the formation of reactive oxygen species, which can play a wide role in host homeostatic signaling and maintenance of normal physiological functions. We are actively exploring how beneficial commensal bacteria modulate these processes. Additionally, pathogenic bacteria are thought to mediate interactions with eukaryotic cells by preformed effector proteins that are translocated into the host epithelia and usurp normal cellular functions. We are also interested in exploiting these proteins as potential therapeutics. The laboratory employs a variety of microbiologic, genetic, biochemical and cell biological techniqu Read more...

    - Dr. Neish's research focuses on the interactions of bacteria with human epithelial cells in an effort to understand the molecular mechanisms of immune and inflammatory reactions that may mediate pathogenic and commensal relationships.


    Pathology Faculty Photo

    Asma Nusrat, MD


    Professor
    Epithelial Pathobiology
    Gastrointestinal Pathology


    Research Interests -

    Epithelial Cell Biology - Our research interests focus on biology of epithelial cells. Epithelial cells in organ systems such as the gastrointestinal and respiratory tracts function as key regulated barriers that interface distinct microenvironments in the luminal vs. the subepithelial tissue compartments. Epithelial barrier function is regulated by a series of intercellular junctions referred to as the apical junctional complex and desmosomes. Our laboratory is studying the structure and function of protein complexes in such intercellular junctions using molecular and cell biologic approaches. We have demonstrated that a subset of apical junctional complex proteins reside in membrane rafts and that they are transported inside cells in distinct trafficking pathways. In addition to mechanical regulation of cell-cell adhesion, intercellular junction proteins function as active signaling centers that regulate epithelial cell differentiation. Dysregulation of such intercellular junction signaling is an important pathobiologic basis for development of epithelial cancers. We are examining the role of intercellular junction proteins in cancer development. An improved understanding of epithelial intercellular association will therefore not only aid in understanding the basic biology of epithelial cell-cell affiliation but will also aid in the design of vaccines and drugs that can be delivered via this route and in development of cancer therapies.

    Other projects in our laboratory are related to the study of mechanisms by which epithelial cells migrate as a cohesive sheet of cells to reseal small wou Read more...

    Epithelial Cell Biology - 1. Molecular characterization, identification and regulation of protein complexes in intercellular junctions of epithelial cells. Relationship of intercellular association, epithelial cell differentiation and oncogenesis.

    2. Molecular mechanisms of epithelial cell migration and polarization.


    Pathology Faculty Photo

    Shoichiro Ono, PhD


    Associate Professor
    Cytoskeleton


    Research Interests -

    Cytoskeleton-Cell Biology - We are interested in the mechanisms of the regulation of actin cytoskeletal dynamics. Actin filaments are reorganized during development, cell migration, and cell division. Proper regulation of the actin reorganization is required for normal celluler activities, while its misregulation often causes diseases. We have been studying functions of actin-binding proteins using biochemical, cell biological, and genetic techniques.

    Alternative pre-mRNA splicing - A number of genes produce mutiple transcripts by alternative splicing. Misregulation of this mechanism is involved in the pathogenesis of myotonic dystrophy. We identified a muscle-specific regulator of pre-mRNA splicing in the nematode C. elegans and have been studying how this splicing factor functions. This splicing factor is conserved in humans, and we hope to gain insights into the mechanism of tissue-specific pre-mRNA splicing.


    Pathology Faculty Photo

    Mirko Paiardini, PhD


    Assistant Professor



    Pathology Faculty Photo

    Charles A Parkos, MD, PhD


    Professor
    Epithelial Pathobiology
    Immunology
    Gastrointestinal Pathology


    Research Interests -

    Pathobiology of leukocyte interactions with mucosal epithelia - Studies in my lab are focused on two areas including the molecular basis of interactions between leukocytes and mucosal epithelia and how such interactions regulate the function of epithelial cells. Specifically, we are exploring how epithelial cells respond to migrating innate immune cells (neutrophils) and on defining the proteins that regulate transmigration of leukocytes across mucosal surfaces that line organs in the gastrointestinal tract and lung. We are particularly interested in the nature of epithelial counterreceptors for migrating neutrophils. Indeed, our recent observations point to a growing importance for a family of transmembrane intercellular junction adhesion molecules termed JAMs that have been shown to function in the maintenance of epithelial barrier and serve as receptors for both migrating leukocytes and viral pathogens. The functional biology of these recently described receptors is just becoming appreciated where we have combined our expertise in epithelial cells and structural/molecular biology to elucidate structure-function relationships in JAMs. We are also studying factors that regulate how fast leukocytes migrate through tissues by modeling how microbial products that activate Toll-like receptors and chemotactic receptors regulate leukocyte transepithelial migration. Our results have linked control of the rate of leukocyte migration to signaling events that occur after ligation of a cell surface protein termed CD47 by its receptor signal regulatory protein alpha (SIRPalpha). These studies directed at understanding the molecular basis of mucosa Read more...


    Pathology Faculty Photo

    Tristram G. Parslow, MD, PhD


    William Patterson Timmie Professor and Chair
    Microbial Pathogenesis
    HIV Pathogenesis


    Research Interests -

    Molecular Virology of HIV and Influenza - Our laboratory's research is focused mainly on the structure and assembly of the human immunodeficiency virus (HIV) and influenza A virus, with the goal of developing new approaches to antiviral therapy. We are particularly interested in understanding how each of these viruses is able to recognize and package its genomic RNA into new viral particles as they form within an infected cell. By combining three-dimensional structural analysis with targeted mutagenesis of virally encoded macromolecules, we are elucidating specific RNA-RNA and RNA-protein interactions that are critical for replication, and that may offer new targets for antiviral drugs.

    My other scientific interests extend broadly over the fields of immunology, virology, and the molecular basis of human disease. Past projects have included studies of human telomerase RNA; of the apoptotic regulatory proteins Bcl2 and Bax; and of immune responses to multicellular parasites; as well as co-discovery of a novel form of human severe combined immunodeficiency (SCID) that results from an inherited defect in ZAP-70, a tyrosine kinase involved in T-cell receptor signaling. In addition, as a pathologist, I have enjoyed several opportunities to collaborate in characterizing novel transgenic or knockout mouse strains whose phenotypes shed light on important facets of mammalian development, immunity, and carcinogenesis.


    Pathology Faculty Photo

    Todd M Preuss, PhD


    Associate Professor
    Neuroscience


    Research Interests -

    Neuroanatomy / Neurohistology / Biomedical imaging / Aging - My laboratory investigates the evolutionary specializations of the human brain. Identifying these specializations is critical for understanding how the human brain supports our unique cognitive abilities and why humans are peculiarly vulnerable to neurodegenerative diseases. We want to know, for example, the extent to which the evolutionary expansion of the human brain was accompanied by the addition of new cortical areas or by the enlargement and internal reorganization of existing areas, and how these changes are related to specializations of cogntion. We also want to understand how the human brain was modified in response to selection for a long life span. For example, how are human neocortical neuronswhich are generated before birth and not replaced during lifeable to survive and function through eight or more decades? Why does Alzheimer's disease occur naturally only in humans? We address questions like these by comparing human brains to those of chimpanzeesthe animals to which humans are most closely relatedand to other nonhuman primates. Within this basic comparative framework, we employ multiple investigative methodologies to identify human specializations at multiple levels of organization: genomic and molecular biological techniques to identify evolutionary changes in gene and protein expression, histological techniques to localize expression changes to specify cell types and cell compartments, and neuroimaging techniques to identify evolutionary changes in connectivity and cerebral morphology.


    Pathology Faculty Photo

    Bali Pulendran, PhD


    Professor
    Immunology
    Vaccines


    Research Interests -

    Immunology/Vaccinology/Virology - In many ways the immune system can be described in anthropomorphic terms: it's memory allows it to remember and recognize pathogens, commensals or vaccines, after years or even decades; it can distinguish between the body's own cells and those of another organism; and it makes decisions about how to respond to particular pathogens. This last characteristic is the focus of our research. Central to the immune system's decision-making process are dendritic cells (DCs), which can sense pathogens, commensals, or vaccines, and orchestrate appropriate immune responses to them. Given their emergence as key regulators of the immune response, there is great enthusiasm for harnessing DCs in the immune therapy of infectious diseases, autoimmunity, allergies, transplantation and cancer [e.g. Pulendran & Ahmed, 2006, Cell. 124: 849; Pulendran, 2004, Immunol. Reviews. 199: 227; Pulendran et al, 2001, Science. 293: 253]. Our research is focused on understanding the fundamental mechanisms by which DCs control innate and adaptive immune responses, as well as in exploiting these in vaccinology and immune therapy. Within this board area, our specific goals are:

    1. To determine the molecular mechanisms and signaling networks by which different microbial stimuli modulate DC function so as to induce strikingly different classes of adaptive immune responses [Th1, Th2, Th17, tolerogenic, or T regulatory responses]. Recent data from our lab suggest that the nature of the particular subset of DC, as well as the type of pathogen recognition receptors (e.g. Toll receptors, C-type lectins) ex Read more...


    Pathology Faculty Photo

    James C Ritchie, PhD


    Professor
    Clinical Chemistry


    Research Interests -

    - My research laboratory is engaged in determing whether the regulation of extracellular peptidase activity plays a significant role in neuropeptide action. In another project, we are focusing on the pharmacokinetics/pharmacodynamics of antidepressants and anti-seizure medications during pregnancy. Finally I am actively pursuing investigations into the use of proteomics as a clinical diagnostic tool.


    Pathology Faculty Photo

    John D Roback, MD, PhD


    Associate Professor
    Transfusion Medicine


    Research Interests -

    Overview - The focus of my laboratory is basic and translational research investigations with an emphasis on improved Transfusion Medicine clinical practice. The primary ongoing projects that have been or are currently NIH-funded include: (i) Utilization of murine models of lethal murine cytomegalovirus (MCMV) disease to develop improved, clinically applicable methods for adoptive antiviral immunotherapy and post-transplant vaccination to for bone marrow transplant recipients; (ii) Development of novel, innovative methods and devices to perform pretransfusion testing of blood components; and (iii) Development of improved PCR methods for screening blood and hematopoietic stem cell products for CMV infectivity.


    Pathology Faculty Photo

    Fred Sanfilippo, MD, PhD


    Professor


    Research Interests -

    Research Interests - Dr. Sanfilippos research projects have included studies in solid state physics, molecular biology and immunogenetics, clinical trials, development of diagnostics and therapeutics, and mechanisms of allograft and xenograft rejection and acceptance. His major research interests in Pathology and Laboratory Medicine have been in immunopathology, transplantation biology, and renal pathology. His current major interests continue to focus on the application of informatics to enhance the quality of healthcare delivery at the level of individuals and populations, and enhancement of organizational performance and culture.


    Pathology Faculty Photo

    Periasamy Selvaraj, PhD


    Professor
    Immunology
    Cancer Biology


    Research Interests -

    Structure and function on Fc receptors - Fc receptors for IgG (FcgR) are involved in phagocytosis, antibody-dependent cellular cytotoxicity, and removal of immune complexes from blood circulation. FcgR III (CD16) is expressed in macrophages, granulocytes and NK cells. CD16 on granulocytes is phosphatidyl inositol glycan (GPI) anchored whereas the CD16 expressed on NK cells and macrophages is polypeptide anchored. These two membrane anchor isoforms of CD16 differ in triggering signals for tumor cell cytotoxicity and phagocytosis. Further structure-function studies will be carried out on membrane isoforms of CD16. We have also identified that the avidity state of FcgRII is regulated by cell activation. Future studies will focus on the defining the molecular mechanisms involved in regulation of affinity of FcgRII molecule expressed on human neutrophils.

    Development of 'artificial cancer cell vaccines' using protein transfer - Tumors modified by transfecting genes for immunostimulatory molecules such as B7 and cytokines are now considered as a potential therapeutic tumor vaccine. However, transfection is not always efficient and can be difficult with many cell types, especially freshly isolated tumor cells from patients. Moreover, transfection of genes requires the introduction of vectors of viral origin which is not desirable for human therapeutic purposes. Studies have shown that purified GPI-anchored cell surface proteins can be spontaneously incorporated into membranes by incubating the proteins with the cells or cell membranes (Protein Transfer). This unique property can be used to reconstitute cell surface expression receptors on cell membranes without the use of gene transfection. Using recombinant techniques, we have developed many immunostimulatory molecules including B7-1, IL-2, GM-CSF and IL-12 as GPI-anchored form. Currently we are using protein transfer to express these molecules to develop cancer vaccines for breast cancer and melanoma. In the long term the knowledge obtained from this study could be used to develop an 'artificial cell vaccine' to treat cancer.


    Pathology Faculty Photo

    Guido Silvestri, MD


    Professor
    HIV/SIV
    Immunology
    Vaccines


    Research Interests -

    HIV/AIDS -

    Immunology of virus infections -


    Pathology Faculty Photo

    Francois J Villinger, PhD


    Professor
    HIV/SIV Pathogenesis
    Immunology


    Research Interests -

    Research interests: Immunology of infectious diseases, AIDS - Adoptive transfer of autologous CD4+ T cells as a platform for immune reconstitution in simian AIDS. My lab has focused on antibody based technologies for expanding and conditioning purified CD4+ T cells from nonhuman primates for the purpose of reconstituting immune responses and enhance control of in vivo viral replication in the primate AIDS model. Using this preclinical model, we have been able to markedly reduce the chronic simian immunodeficiency viral replication and disease progression in the absence of prolonged chemotherapy. My lab now strives to define the function and characteristics of the expanded cells as well as their fate in vivo.

    A second focus of the lab is its role as a "Resource for nonhuman primate immune reagents" including the creation of a repository for primate cDNA clones, the construction of DNA vectors for the expression of such NHP molecules and the production and testing of monkey recombinant cytokines. The need for this NCRR funded resource was borne from the realization that human cytokines are generally immunogenic when used in monkeys, thus severely limiting the value of these model for immunotherapies. Reagents generated are distributed either freely or at production cost to other PHS funded investigators.


    Pathology Faculty Photo

    Ifor R Williams, MD, PhD


    Professor
    Immunology
    Epithelial Pathobiology
    Clinical Immunology


    Research Interests -

    Mucosal Immunology; Chemokine Receptors; Lymphoid Organogenesis - The major areas my laboratory studies are: (1) the role of chemokines and chemokine receptors including CCR6, CCR9, and CCR10 in mucosal immunity; and (2) the cellular interactions, cytokines, and chemokines involved in initiating the development of the lymphoid aggregates present in the small intestine including cryptopatches and isolated lymphoid follicles.


    Pathology Faculty Photo

    Keqiang Ye, PhD


    Professor
    Neuroscience
    Cancer Biology


    Research Interests -

    How NGF regulates neuronal cell survival in the nucleus - To study neurotrophin signalings in neuronal cell survival and drug discovery in neuroprotection. To dissect the physiological roles of PIKE in tumorigenesis and anti-cancer drug development To determine the neuronal cell death molecular mechanisms of neuroexcitotoxicity and stroke in central nervous system and drug discovery


    Pathology Faculty Photo

    Andrew N Young, MD, PhD


    Associate Professor
    Cancer Biology
    Clinical Pathology


    Research Interests -

    Primary Focus - Molecular classification of kidney cancer by gene expression profiling. - My research laboratory has developed systems for molecular classification of renal tumors using cDNA and oligonucleotide microarrays. Based on gene expression profiles, we have identified numerous immunohistochemical markers for diagnosis and clinical management. Currently, we are developing novel Raman-active nanoparticle-based immunoassays for renal tumor classification using fixed tissue and fluids.