Samir Acharya My broad research interest is to understand the fundamental biochemical mechanisms underlying genomic instability and cancer susceptibility of cells. The current focus of my laboratory is to define the biochemical mechanism of DNA mismatch repair and its role in signaling DNA damage, using Escherichia coli as a model. Our long-term goal is to understand how the different DNA repair pathways interact with the cellular metabilic pathways to achieve a finely regulated system of cellular propogation.

Rita Alevriadou Research area: Research in the Vascular Bioengineering Laboratory (Dr. Alevriadou’s lab) focuses on the effect of hemodynamic forces (fluid shear stress) or oxidative stress on: (a) the intracellular signal transduction, gene expression and protein synthesis of vascular endothelial cells, and (b) the molecular mechanisms of adhesive interactions between blood cells and other blood cells, vascular cells or extracellular matrices. Our immediate goal is to understand the role of endogenous reactive oxygen species in cultured endothelial cell dysfunction when exposed to changes in both oxygen tension and fluid flow. The long-term objective is to propose better prevention and treatment strategies for cardiovascular diseases, in particular for the ischemia/reperfusion-induced vascular injury. 

Ruth Altschuld Dr. Altschuld’s research deals with cellular changes in heart failure and myocardial infarction, with special emphasis on calcium cycling and adrenergic reactions.

Amal Amer My work is focused on the innate immune response to Legionella pneumophila and Burkholderia cepacia infections. Legionella is the causative agent of Legionnaire's disease and B cepacia is the causative agent of cepacia syndrome in cystic fibrosis patients. We are investigating the details of the molecular mechanism by which these two lung pathogens can evade the host response and survive inside macrophages.

Clark Anderson Dr. Anderson is interested in how IgG antibodies work; specifically, how they mediate inflammatory and protective effects, how they are degraded, and how they are transported across the fetus from maternal to fetal circulation.

Candice Askwith Research area: My research interests focus on the role of ion channels in synaptic plasticity and sensory transduction. Specifically, we investigate how the acid-sensing ion channels (ASICs) affect learning and memory, mechanosensation, and pain using electrophysiology, mouse genetics, and molecular biology.

Leona Ayers Research focuses on the pathology of the rapid progression of both benign and malignant diseases in the HIV infected individual. Of specific interest is the role of monocytes infected with both HIV and Chlamydia pneumoniae in CNS lymphoma and pulmonary emphysema. Pathology investigations are tissue based and feature the use of tissue microarrays.

Xue-Feng Bai Research area: We study T cell responses in autoimmune diseases and cancer. We are particularly interested in the molecular mechanisms that govern T cell effector functions in the inflamed central nervous system or tumor.

John Barnard Research Area: The Barnard laboratory is interested in the cell biology of intestinal epithelial proliferation and how intestinal cells become resistant to inhibition by transforming growth factor (TGF) beta. Using cell culture models of Ras-transformation, they are determining the precise points in TGF beta signaling that are disrupted by oncogenic Ras. In addition, interactions between the Ras pathway and the Rho signaling pathway are being examined. Dr. Barnard?s studies are relevant to the biology of colorectal cancers, 90% of which are resistant to growth inhibition by TGF-beta.

Sanford Barsky Dr. Barsky's major research interests are Basic Molecular Mechanisms of Tumor Invasion and Metastis, Inflammatory Breast Cancer research and Lung Carcinoma. Dr. Barsky's lab is also interested in stem cells and high throughput tissue processing and image analysis as it relates to the processes of tumor progression and metastasis.

Rolf Barth Dr. Barth?s research focuses on innovative treatments for brain tumors, specifically boron neutron capture therapy (BNCT) and gene therapy. The major emphasis is on the development of effective strategies to target either the boron capture agent or gene vector to the tumor.

Christopher Bartlett My laboratory seeks to identify genetic factors for language impairments. As animal models of language development are of limited utility, we examine DNA from families segrating specific language impairment or autism as part of two separate but interacting projects. These projects are heavily interdisciplinary, utlizing a wide range of molecular and computational methods developed in-house and through close collaborations with experts in statistics and computer science. We hope that use of genetics will allow for identification of at-risk children to promote early intervention.

Jeffrey Bartlett Research Area: The research in Dr. Bartlett?s laboratory focuses on the development of viral vectors for human gene therapy. Most of their work involves adeno-associated virus (AAV) vectors, although they also work with adenovirus vectors and molecular targeted viral conjugates. The laboratory has active and funded research programs in cystic fibrosis gene therapy, and in gene therapies for the treatment of brain and ovarian cancers. A main interest of the laboratory has been to define the endogenous tropism of viral vectors as a basis for subsequent modifications to alter host cell range. Research has focused on the development of targetable vector systems and the biodistribution and sub cellular fate of gene therapy vectors in vivo. This work has led to the development of novel technologies for the cell-specific delivery of gene-medicines and the pharmacological analysis of virus-mediated gene therapies.

Michelle Basso This lab is part of the Spinal Trauma and Repair group and my research examines the neuroanatomical and cellular substrates of recovery of function after spinal cord injury (SCI). We are interested in the development, maintenance and treatment of neuropathic pain after SCI and investigate neuroinflammatory mechanisms in animal models. We are also interested in the role of treadmill training in improving sensory and motor function in humans and animals with SCI.

Carl Bates Dr. Bates is an Investigator, Center for Cell and Developmental Biology, Columbus Children?s Research Institute and Assistant Professor of Pediatrics, Division of Nephrology, Department of Pediatrics, College of Medicine, The Ohio State University. The focus of Dr. Bates? research is on genes critical for kidney development. In particular, the main genes of interest are the fibroblast growth factor receptors (FGFRs). Using a conditional knockout approach in mice, the laboratory has discovered that FGFRs in the metanephric mesenchyme are critical for early kidney patterning events in both the mesenchyme and ureteric bud. FGFR2 in the ureteric bud is necessary for proper patterning of the ureteric bud tree and the stromal mesenchyme. In addition, loss of FGFR2 in the ureteric bud leads to a decrease in nephron number in utero which is associated with hypertension and renal failure in adult mice.

Christine Beattie Research area: Our goal is to understand the genetic and molecular programs that enable motor axons to extend to the correct muscles during normal development and in motoneuron diseases. In particular, we focus on tow motoneuron diseases spinal muscular atrophy (SMA) and amyolateral sclerosis (ALS) and use genetic and molecular approaches to understand the biology of these diseases. We use zebrafish as a vertebrate model organism due to its well characterized nervous system and its relatively simple neuromuscular organization.

Charles Bell Research area: Research in the Bell Lab is focused on the structural biology of homologous recombination, an important mechanism in all cells for repairing double-stranded DNA breaks. One area of interest is the E. coli RecA protein, which is important as a model system for understanding the underlying mechanistic principles of homologous recombination. The research combines the powerful technique of x-ray crystallography to obtain high resolution structural information, with other biochemical and biophysical methods to arrive at a complete understanding of the structure/function of RecA and other proteins involved in this important DNA repair process.

Gail Besner Research area: Dr. Besner?s research involves a growth factor known as heparin-binding EGF-like growth factor (HB-EGF), and its ability to protect against intestinal ischemia/reperfusion injury. The lab conducts both in vitro and in vivo studies, the latter using animal models of intestinal ischemia/reperfusion injury, to study the protective effects of HB-EGF on intestinal injury. Studies focus on the effects of HB-EGF on nitric oxide and oxygen free radical production, apoptosis, bacterial translocation, cell proliferation and migration and signal transduction pathways.

Thomas Best Our research focuses on the role of inflammatino in muscle stretch injury and repair. We utilize an animal model to understand injury mechanisims and the role of neutrophils in promoting injury and repair. Cell signaling mechanisms that control neutrophil activation and subsequent myofiber death are investigated through in vivo and in vitro approaches. The goal of our translational work is the development of scientific-based strategies to limit muscle damage and enhance repair.

David Beversdorf Research area: Our lab examines noradrenergic modulation of problem solving ability, with applications in autism and cocaine withdrawal, and problem solving ability in cocaine withdrawal, autism, and mild cognitive impairment using neuropsychological testing, functional neuroimaging and microelectrode array analysis.

George Billman The primary focus of Dr. Billman?s laboratory is to investigate the mechanisms responsible for ventricular fibrillation induced by either myocardial ischemia or cocaine toxicity. Particular emphasis is placed on the role that changes in ion channels and intracellar calcium homeostasis play in these malignant arrhythmias.

Philip Binkley 

PHILIP BINKLEY (Internal Medicine)  My laboratory and research program is devoted to translational investigation of the pathophysiology of congestive heart failure and dilated cardiomyopathy.  This research ranges fr om investigation of genomic determinants of clinical outcome to identification of novel clinical variables determining response to therapeutic strategies for the management of heart failure.

Dan Birmingham Research Area: Dr. Birmingham?s research focuses on the genetic and biological basis for human immune complex diseases, such as the autoimmune disease systemic lupus erythematosus and various forms of immune complex nephritis. The current thrust of this research is the identification and characterization of polymorphic forms of complement, complement receptors, and Fc receptors as genetic risk factors for these diseases. These studies range from basic bench top research, to primate models of immune complex disease, to translational research involving a large accessible patient population.

Georgia Bishop Research Area: My laboratory uses physiological, immunohistochemical and biochemical techniques to analyze the role of the cerebellum in controlling movement. In addition, we focus on factors that influence development including peptides which we believe act as neurortropic factors during development and as neuromodulators in the adult. In addition, we are initiating studies to determine how the anti-convulsant drug, valproic acid, alters cerebellar circuits during development and in the adult.

Michael Bissell Dr. Bissell?s informatics interests are focused on humanistic aspects of laboratory medicine and medical informatics: laboratory-related measures of patient outcomes evidence-based laboratory medicine, medical error and patient safety, automation and human factors/ergonomics, quality assessment and clinical laboratory ethics.

Laura Bohn Research area: The Bohn lab asks how opiate narcotics, such as morphine, methadone and heroin, mediate physiological effects such as pain relief, tolerance, dependence and addiction. Morphine activates the mu opioids receptor which is a member of the G protein-coupled receptor (GPCR) family and is subject to cellular regulation, an event that can determine the potency of the drug. Utilizing signal transduction assays in cell cultures combined with behavioral and physiological testing in genetically modified mice, we study the contribution of receptor regulation to the overall effect of opiates.

Kathleen Boris-lawrie Genetic, biochemical and genomic approaches are being used to understand post-transcriptional control mechanisms used by retroviruses and their host cells to modulate viral infection and control cellular growth. A major emphasis of the lab has been on our discovery of a novel post-transcriptional control element that is conserved in selected retroviruses and naturally intronless cellular mRNAs. This novel RNA element is positioned at the extreme 5' terminus of the mRNA and functions in a cap-dependent manner to stimulate translation. Using proteomic approaches, we have identified RNA helicase A (member of DEAD box superfamily) is an essential PCE effector protein. RNA helicase A is recruited to PCE in the nucleus and subsequently operates a binary switch that facilitates translational activity of this mRNA in the cytoplasm. In addition to investigating the molecular mechanism of selective translational control, the lab is implementing PCE as an important component of an unique class of hybrid retroviral vector that replicate the structural genes of bovine leukemia virus (BLV) and new HIV-based lentiviral vectors with improved protein synthetic activity.

Jack Boulant Research area: Hypothalamic neurons control several regulatory responses, including body temperature and fever. Electrophysiological recordings use intracellular & extracellular microelectrodes in rat hypothalamic tissue slices. Neurons are tested for their responses to temperature, osmolality, glucose, hormones, fever-producing agents, neurotransmitters, as well as substances affecting cyclic AMP and synaptic connections between nearby neurons.

R. Thomas Boyd Research area: Molecular neurobiology, regulation of genes encoding neuronal nicotinic acetylcholine receptors, characterization of nicotinic receptors on adrenal chromaffin cells and investigating the role of neuronal nicotinic acetycholine receptors in zebrafish development.

William Brantley The principle focus of my research is fundamental investigation of the complex relationships among compositions, microstructures, mechanical properties, biological properties and clinical performance of dental alloys, using transmission electron microscopy, scanning electron microscopy, x-ray diffraction, metallographic techniques, a variety of mechanical testing procedures, and cell culture techniques. Current activities are centered on palladium-based casting alloys used for metal-ceramic restorations and implant-supported prostheses and on alternative techniques to casting for the fabrication of titanium alloys for orthodontic wires and endodontic instruments, and the use of thermal analysis techniques to investigate the structures and properties of elastomeric dental materials.

Roger Briesewitz Research area: Mutationally activated tyrosine kinases are involved in the genesis of multiple cancers. The inhibition of mutated kinases with small molecule inhibitors can induce apoptosis and can provide a significant therapeutic benefit to cancer patients. The Briesewitz lab is focused on understanding the mechanism by which mutated kinases contribute to oncogenesis and why their inhibition results in apoptosis. The obtained insights may suggest novel therapeutic approaches.

Anthony Brown Our laboratory uses state-of-the-art digital fluorescence imaging techniques combined with molecular, biochemical and ultrastructural approaches to investigate the axonal transport of cytoskeletal and cytosolic proteins in nerve cells. We are particularly interested in the axonal transport of neurofilaments because an impairment in the movement of these cytoskeletal polymers has been implicated in the etiology of a number of neurodegenerative diseases. The long-term goal our research is to define the molecular mechanisms by which cytoskeletal and cytosolic proteins move in neurons and the mechanisms by which this movement is regulated, both in health and disease.

John Buford Dr. Buford studies the neural control of movement, currently focusing on the role of reticulospinal neurons in skilled reaching. He employs techniques from neurophysiology, neuroanatomy, neuropharmacology, and biomechanics in a non-human primate model.

Ginny Bumgardner The focus of research in Dr. Bumgardner?s laboratory is to elucidate mechanisms of immune recognition and destruction which target liver and pancreatic parenchymal cells. In addition, the laboratory is designing strategies to circumvent these mechanisms in order to protect liver cells and islet cells from immunologic damage under a variety of settings (alloimmunity, autoimmunity, and virally infected cells).

Arthur Burghes The main focus of the laboratory is the molecular understanding of genetic neuromuscular disorders. In particular, the laboratory focuses on unraveling the molecular biology of Spinal Muscular Atrophy (SMA). SMA is an autosomal recessive disorder that is characterized by destruction of motor neurons in the anterior horn of the spinal cord. The disorder can be classified according to clinical severity into three types. SMA is caused by loss or mutation of the SMN1 gene but not the virtually identical SMN2 gene. The two genes essentially differ by a single nucleotide that affects the incorporation of exon 7 into the SMN message. This results in the SMN2 gene producing insufficient SMN protein for motor neurons. SMN functions in the biogenesis of SnRNPs which is essential for all cells, currently it is not clear why high SMN levels are so critically important for motor neurons.

We have developed an animal model of SMA in the mouse and shown that high copy number of the SMN2 gene can rescue the SMA mouse. We are using this animal model of SMA to understand why motor neurons are affected and to develop treatments for SMA. A high throughput screen to identify compounds that can activate SMN has been started. It is hoped that these compounds can act as therapeutic reagents for SMA.

The laboratory is also developing gene therapy methods for treatment of Duchenne Muscular Dystrophy (DMD). DMD is a muscle wasting disorder caused by mutations in the large dystrophin gene. We are particularly interested in developing strategies that allow Adeno Associated Virus to be used for gene therapy of DMD.

Richard Burry Work in Dr. Burry?s lab examines the role of cell signaling in the differentiation of neurons and glia. They are examining the cellular responses of neurons to known growth factors and to other proteins that could function as growth factors.

John Byrd Research area: The Byrd laboratory is both a basic and applied translational laboratory with three major research focus areas including 1) investigation of the mechanisms by therapeutic monoclonal antibodies mediate their cytotoxic effects in leukemia cells and how resistance to these develop; 2) In vitro and in vivo studies of drug development focused on targeted therapies (chromatin remodeling agents and signal transduction inhibitors) in leukemia; and 3) Applied molecular characterization of different genetic and epigenetic abnormalities in chronic lymphocitic leukemia with application to their importance in disease progression and response to chemotherapy and biologic agent utilized for treating this disease.

Michael Caligiuri The Caligiuri laboratory has three funded areas of basic and translational research. The first deals with lymphocyte biology, in that they characterize cytokine receptors on human natural killer cells and work to elucidate the functional consequences of the ligand binding to the receptor. The second area of focus is elucidating the molecular mechanisms involved in the pathogenesis of leukemia. Much of their work is translated into clinical trials.

William Carson Our laboratory is interested in the interactions that occur between the immune system and cancer cells. We have three ongoing projects that began as basic in vitro observations that have not been translated into the clinical setting. One major area of research involves the use of cytokines to enhance the anti-tumor actions of interferon-alpha. A second area of research in our laboratory involves the use of cytokines to enhance the actions of anti-tumor monoclonal antibodies. A third area of interest is the effects of stress on the immune system of patients diagnosed with cancer. Projects in development include studies of tumor angiogenesis and vaccine development.

Umit Catalyurek My research interest includes high-performance data-intensive computing, medical informatics, graph and hypergraph partitioning, domain decomposition methods for parallel computing, runtime systems for parallel machines and combinatorial algorithms. My current research focuses on the development of systems software for efficient storage and processing of very large scientific datasets on high-performance machines.

Dawn Chandler Dr. Chandler's laboratory is primarily interested in the regulation of pre-mRNA splicing and how disruption of this regulation can lead to pediatric diseases such as cancer. In addition, the lab is studying Proximal Spinal Muscular Atrophy (SMA), the leading genetic cause of infant mortality in humans, which is in part due to a mutation that affects splicing of a duplicated gene that controls neuronal growth (SMN2). The increase awareness of regulated RNA processing and recent indentification of several disease-causing mutations that affect splicing give rise to a new generation of potential therapeutic targets.

Long-sheng Chang Reinoblastoma-family suppressor gene function and regulation during the cell cycle; Neurofibromatosis type 2 gene in Schwannomas; Neural-specific serotonin 5-HT2C receptor expression.

Yeong-Renn Chen Dr. Chen's research is focused on bioenergetics and free radical metabolism in postischemmic injury. Our long-term goal is to understand the molecular mechanism of how mitochondria-derived oxygen free radical(s) and post-translational redox modifications are related to the pathogenesis of myocardial injury. Specifically, we have used the model systems of isolated enzyme, in vitro and in vivo myocardial postischemic rat hearts to test our hypothesis.

Louis Chicoine Our lab is focused on the study of normal and abnormal lung and lung vascular development as related to pulmonary endothelial nitric oxide synthase (eNOS) and its regulation of pulmonary vascular tone. In addition, we are studying novel approaches to the treatment of pulmonary hypertension utilizing gene therapeutic approaches. Several ongoing studies using models ranging from cell culture to isolated lung to whole animals, and techniques ranging from RNA interference to physiological studies are directed at answering questions relating to eNOS expression and NO production, and their effect on pulmonary artery tone during development.

E. Antonio Chiocca Dr. Chiocca's group has been interested in the biology and therapy of malignant tumors of the brain, such as glioblastoma. Currently funded NIH projects are: 1) studying the role of a number of genes involved in glioma and neural stem cell invasion and migration in normal brain in order to model brain tumor infiltration with computer simulations; 2) engineering tumor-killing viruses for experimental treatment of gliomas; and 3) understanding the role of the innate immune system and the host of stroma in gene-and viral-based therapies against these tumors.

Ing-ming Chiu Research area: Neural stem cell biology and stem cell-based therapy in neurodegenerative diseases and controlling mechanism of gene expression of fibroblast growth factor 1 in cancer and in neural development.

STEVEN CLINTON (Internal Medicine)  Our laboratory program focuses upon the etiology, prevention, and treatment of prostate and other genitourinary cancers.  The role of diet and nutrition in carcinogenesis is a major research interest.  Laboratory efforts involve molecular techniques, cell culture, rodent models, translational human clinical trials, and epidemiology.

Helen Cooke Neural reflex regulation of intestinal secretion; the regulation of serotonin release and its role in neural reflex control of the gut; the coordination of secretion and motility.

Estelle Cormet-Boyaka The main focus of the laboratory concerns the biology of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR), a chloride channel implicated in Cystic Fibrosis (CF). The most common mutation causing CF is due to a trafficking defect of the CFTR protein that fails to reach the plasma membrane and is retained in the endoplasmic reticulum. Our research focuses on the trafficking of CFTR, and understanding the role of protein-protein interaction in the biosynthesis pathway of CFTR.

Steven Dambrosio Mechanisms of DNA damage and repair in relationship to geno-toxicity, and cancer initiation and promotion and treatment. Mechanisms of agents used in cancer prevention

Douglas Danforth Research area: Research in my laboratory focuses on the regulation of early follicle growth in the mammalian ovary. We are interested in how the regulation of angiogenesis and vascular permeability modify the growth and survival of primordial and primary follicles. Specifically, the roles of Vascular Endothelial Growth Factor (VEGF) and Endocrine Gland VEGF (EG-VEGF) in rodent and domestic animal reproductive physiology are studied.

Jonathan Davis Determine the cellular and molecular basis of muscle contraction and relaxation. Understand how calcium binding proteins/enzymes are appropriately "tuned" kinetically to respond to calcium transients in vitro and in vivo. Modulate cellular function through the design and engineering of calcium binding proteins.

Ramana Davuluri Bioinformatics and Computational Biology. Topics of interest currently pursued are: computational identification of first exons and promoters in the human genome and development of computational tools for modeling genomic, pathway and interaction information, such as metabolic pathways and genetic regulatory circuits.

Robert Dephilip The role of a class of cell adhesion molecules called cadherins in development of the gonad and in cancer.

Andrea Doseff My laboratory investigates the mechanisms involved in cell death during the innate immune response and oncogenic transformation. We combine molecular, biochemical, cellular biology and bioinformatics approaches to understand the regulation of the apoptotic pathways.

Our studies are focused on the signaling pathways that contribute to the activation and deactivation of caspases, essentials proteases required for apoptosis. The main purpose of our research is that by understanding the mechanisms that regulate the caspases we will be able to manipulate cell death of unwanted cells as a treatment for cancer, inflammation and formation of the atherosclerotic plaque.

One major project in my lab is to identify the proteins that regulate the activation and activity of the inflammatory and killing caspases during monocyte-macrophage-dendritic cell differentiation. This includes the isolation of regulatory proteins and the dissection of the signaling pathways that modulate apoptosis.

We showed that some PKC isoforms act as pro-apoptotic factors phosphorylating caspase-3 and promoting its activity. These pathways may change during differentiation thus allowing the cells to regulate their apoptotic commitment differently depending on their differentiation’s stage.

We have demonstrated a differential role of inflammatory and anti-inflammatory cytokines in the control of the apoptotic machinery of leukocytes.

Furthermore, plant flavonoids are being investigated due to their potential to induce apoptosis in cancer cells and decrease inflammation. These findings may provide a new approach
to regulate the number of unwanted cells during inflammation.

In this context, one of our main interests is to understand the role of kinases, phosphatases and reactive oxygen species in the regulation of caspases and the contribution of the mitochondria during activation and monocyte apoptosis. These results should contribute to a better understanding of basic mechanisms during sepsis, cancer and the formation of the atherosclerotic plaque.

A second area of research involves the characterization of signals produced by dying cells to recruit and promote the clearance of apoptotic bodies by phagocytic cells like the macrophages. We are using biochemical and a proteomic approaches to characterize a compounds produced by dying cells that are chemotactic for macrophages. In addition, using a bioinformatics approach and with the availability of the human proteome, we are trying to characterize new substrates of caspases. These ‘in-silico experiments’ should allow us to identify additional targets of caspases that once validated molecularly can be used to mark unwanted cells for removal by phagocytic cells.

Jennifer Edwards We are interested in interactions occurring between the pathogenic Neisseria and their sole human host. Specifically, we are elucidating the signaling pathways and the host and bacterial responses initiated with infection, how neisserial and host constituents contribute to and subvert these responses to potentiate infection, and the efficacy of innate defense mechanisms in neisserial killing.

Heithem El-Hodiri Research area: Our research centers on regulation of anterior neural development by developmentally regulated transcription factors. We are currently focusing on the retinal homeobox (Rx) and aristaless-related homeobox (Arx) genes, members of a subfamily of paired-type homeobox genes. We hope to understand the mechanism by which these and other anterior neural-specific transcription factors regulate development of the eye and forebrain

John Enyeart My research is focused on the hormonal control of ion channel function and gene expression in endocrine and neuroendocrine cells. Ongoing research incorporates a range of electrophysiological and molecular techniques and skills, all of which are performed routinely in my laboratory. Electrophysiological techniques include whole cell and single channel patch clamp recording from primary and cDNA-transfected cells, and patch clamp recording from tissue slice preparations. Molecular techniques include tissue culture of primary cells and cell lines, cDNA cloning, PCR, Northern and Western blots, and gene silencing using siRNAs.

Richard Fertel Macrophages produce nitric oxide in response to stimulation by a variety of factors. The stimulatory effects of interferon y and lipopolysaccharide on the macrophage can be distinguished by their differential response to adenosine. Dr. Fertel's current work is focused on the role and mechanism of action of adenosine in the activation of macrophages.

Andy Fischer Research area: My research interests focus on the neural development, regeneration, and survival of cells in the retina. In particular, I am studying neural stem cells that are found at the peripheral edge of the retina or those that are derived from the major type of glial cell in the retina, the M?ller glia. I am investigating the cellular and molecular mechanisms that control the proliferation and differentiation of neural precursors in the developing and mature retina.

Richard Fishel My laboratory studies the genetics, regulation, mechanism, and consequences of human DNA repair. We primarily focus on the role of DNA repair in the pathogenesis of cancer and HIV infection as well as the role of DNA repair in accurate meiotic chromosome segregation and fertility. We work with a collection of over 50 human DNA repair genes using state-of-the-art biophysical, genetic, and cellular methods.

Emilio Flano Research area: Our laboratory studies the interaction between the immune system and chronic viral infections. We use a mouse model of gamma-herpesvirus infection to analyze diverse aspects of the immune response. Gamma-herpesviruses are DNA tumor viruses that establish latent infections for the life of the host using multiple immune evasion mechanisms, and are associated with numerous lymphoproliferative diseases. Specifically, we have three areas of research: i) study the role of dendritic cells in the initiation of the immune response and their interaction with the virus, ii) analysis of the T cell immune control and generation of memory, and (iii) analysis of vaccine strategies using dendritic cells as adjuvants.

Michael Freitas Our group has developed extensive expertise in the field of clinical proteomics, biomarker discovery/validation and bioinformatics for mass spectrometry based proteomics. Our work focuses chiefly on the determination of side chain modifications of proteins important in Chromatin Remodeling and relating these modifications to aberrant cellular function. Understanding the Molecular Structure of these proteins is critical to deducing their role in transcription

Haiyan Fu Research area: Strategies for global delivery of the adeno-associated viral (AAV) vectors into the central nervous system (CNS) and the therapeutic impacts of AAV CNS gene delivery for treating neurological and somatic disorders of the mucopolysaccharidosis (MPS) IIIB. The goal is to develop gene therapy for treating MPS IIIB patients.

Jian-Xin Gao Research area: Since cancer and autoimmune diseases reflect opposite states of immune response, we are interested in how innate and adaptive immune systems are compromised during the occurrence of autoimmune disease and/or cancer. Specifically, we are focused on the alterative interactions between monocytes/dendritic cells (DC), natural killer cells (NK) and T cells during disease development. The study will facilitate the design of a novel, efficient immunotherapeutic strategy for cancer and autoimmune diseases.

Pedram Ghafourifar Our lab is studying the biology of mitochondria and nitric oxide. We are interested in the interactions of nitrogen oxide species with the mitochondria. We are studying the functions of the mitochondrial nitric oxide synthase (mtNOS) for physiological cellular functions

Ronald Glaser The research project in Dr. Glaser?s lab concerns the interaction of the central nervous system, immune system, and endocrine system and how behavioral factors such as stress influence these complex interactions. The implications of this multidisciplinary research impact on wound healing, reactivation of latent herpes virus, and risk for infectious disease and cancer.

Jonathan Godbout Research area: The elderly are more susceptible to peripheral infections and have increased incidence of neurological problems following these infections including depression, cognitive decline, and potentially the onset of neurological disease. Therefore, the research focus of our laboratory is to understand how age-associated changes in the central nervous system impair the coordinated psycho-neuro-immune response to peripheral infection. We are using an integrative approach using molecular, cellular, and behavioral techniques to address these issues.

Keith Gooch Research in Dr. Gooch's laboratory focuses on the regulation of the differentiation, growth, and remodeling of cells and tissues. These studies span various length scales ranging from the macroscopic level (e.g. mechanical regulation of vascular remodeling) to the tissue-level (e.g. role of adhesion and matrix stiffness in regulating capillary and islet morphogenesis) to the molecular (role of specific transcriptional factors in pancreatic endocrine development). While many of these studies focus on issues related to biological effects of mechanical effects, the role of oxygen tension in regulating pathological vascular remodeling is a growing research focus.

Joanna Groden The Groden Laboratory is focused on understanding some of the factors that confer inherited susceptibility to cancer, with an emphasis in the area of gastrointestinal cancers. The use of mouse models of cancer are heavily incorporated into our approaches which also include biochemistry, cell biology, and molecular biology. We study Bloom's syndrome and familial adenomatous polyposis coli, two inherited syndromes which confer susceptibility to cancer through alteration of the Blm helicase and chromosome stability, and the APC tumor suppressor, respectively. These proteins provide important clues to understanding some of the mechanisms by which the integrity of our genetic material, and appropriate cell growth and differentiation are maintained.

Chen Gu Our research is focused on the mechanisms underlying polarized targeting of ion channels in neurons, and related neurological disease. Currently, we are investigating the roles of cytoskeleton-associated proteins in potassium channel axonal-dendritic targeting, and how myelination regulates axonal ion channel targeting and function, using molecular biology, cell biology, neuronal culture, imaging techniques and animal model.

Howard Gu  Research area: Currently there are three research projects: (1) we are in the process of making a knock-in mouse model carrying a cocaine resistant functional dopamine transporter (DAT) to study the role of DAT in cocaine addiction; (2) in collaboration with the scientists and clinicians in the department of Psychiatry, we are screening patients with mental disorders for single nucleotide polymorphisms (SNPs) in critical genes to uncover the genetic basis of certain mental disorders; (3) we have engineered a functional DAT construct with all reactive cysteine residues removed which allow us to study the 3-D structure of DAT, where cocaine binds, and potentially what new drugs can be developed to treat cocaine addiction.

John Gunn  Research area: Dr. Gunn?s laboratory is primarily interested in the molecular mechanisms used by Salmonella spp. to survive harsh conditions it encounters within the human host, including those within the gallbladder and within the macrophage phagosome. Attenuated Salmonella-based vaccines are also a focus of his group. Finally, Dr. Gunn?s laboratory is interested in pathogenesis and intramacrophage survival of the Category A biodefense agent, Francisella tularensis.

Metin Gurcan Dr. Gurcan's research interests include image analysis and understanding, computer vision with applications to medicine; computer-aided detection and diagnosis (CAD) of cancer. He has developed CAD systems for different organs such as breast, lung and colon, using different modalities such as mammography and CT; and for both in vivo and microscopic imaging systems. CAD development requires interdisciplinary research; therefore, Dr. Gurcan's research experience covers a wide variety of interrelated research fields such as multi-resolution image decomposition, adaptive filtering, statistical pattern recognition, neural networks, image and volume registration, morphological image processing, multi-dimensional optimization, image segmentation, and statistical signal processing.

Denis Guttridge Research area: Our laboratory is interested in the function of the transcription factor NF-kappa B in regulating cell growth and differentiation. We are also involved in how this transcription factor regulates skeletal muscle differentiation and how skeletal muscle undergoes wasting in cancer patients in a condition referred to as cachexia.

Sandor Gyorke Dr. Gyorke's laboratory is interested in molecular mechanisms of excitation-contraction coupling and intracellular calcium handling in the heart. A comprehensive approach is used including life cell imaging, electrophysiology and adenovirus-mediated gene transfer to define the function of individual calcium regulatory proteins and how genetic defects in these proteins lead to altered calcium handling, arrhythmia and sudden death. Another line of studies is directed toward understanding the role of alterations in calcium signaling in heart failure.

Maria Hadjiconstantinou - Neff Research is focused on cellular and molecular neurochemical pharmacology, trophic factors and signal ling cascades. Current projects investigate neurodegenerative processes and repair, aging, nicotine addiction and regulation of biogenic amine synthesis.

Gregg Hadley Dr. Hadley's research program is focused on defining immunologic mechanisms underlying: 1)rejection of transplanted tissue and organs, and 2) graft-vs-host disease elicited following hemotopoietic stem cell transplantation. These studies employ rodent transplant models but where possible specimens from normal humans and clinical transplant recipients are utilized to confirm relevance of key findings to the human system. The ultimate goal of these studies is to advance human health by identifying the means for specific therapeutic intervention in the immunologic problems associated with transplantation of tissues between individuals.

Tsonwin Hai Research area: We are studying how the cells respond to stress signals and how their responses play a role in the development of diseases. The cellular processes we study include stress-regulated signal transduction, gene expression, cell cycle progression, and apoptosis. Our current interests of disease are cancer and diabetes.

Brett Hall Our laboratory is investigating the relationship between metastic tumor cells and tumor associated fibroblasts in solid tumors. The current focus is to expand our fluorescent-based in vitro and in vivo model systems, which will allow us to study the earliest mechanisms of metastatic tumorgenesis. Characterization of these early events in cancer metastasis will be critical for development of novel cancer treatment stategies targeted at permissive tumor microenvironments.

Scott Harper Dr. Harper's laboratory studies gene therapy for dominant genetic diseases using RNA interference (RNAi), with particular focus on muscular dystrophy and neurodegenerative disease. The Harper lab utilizes a broad range of tools, including molecular biology, biochemistry, RNAi, gene therapy vectors, and animal models for muscular dystrophy and peripheral neuropathy.

Randall Harris My research is focused on cancer prevention and therapy through use of compounds with anti-inflammatory activity. Our epidemiologic and preclinical investigations continue to indicate that nonsteroidal anti-inflammatory drugs (NSAIDS) have significant antineoplastic activity against cancers of the breast, prostrate, colon, lung, and many other neoplasms, principally through blockade of cyclooxygenase-2 (COX-2) and other molecular targets of the inflammatory cascade.

Paul Henion Dr. Henion?s laboratory uses genetic approaches in zebrafish to elucidate the mechanisms that regulate cell diversification. We study topics such as establishment of the embryonic axes, induction and fate specification of the neural crest and hematopoiesis.

Gail Herman Research area: Research in Dr. Herman?s laboratory is focused on understanding the pathogenesis of selected human developmental disorders using the mouse as a model system. Current projects involve the study of 2 X-linked mouse models of disorders involving enzymes of cholesterol synthesis that are associated with prenatal male lethality and skin, skeletal, and eye defects in surviving heterozygous females. A second project involves the study of the role of the hedgehog signaling pathway in early placental development. Finally a more clinical, collaborative project is focused on genetic factors involved in autism.

Charles Hitchcock Dr. Hitchcock?s interests focus on the use of various tools, especially cytology and cytometry, to detect metastatic disease in patients with colorectal or breast cancer. A second area of research deals with informatics and the development of computer based education tools.

Kun Huang Research area: My research areas include computer vision, image analysis, machine learning, and system theory. I am particularly interested in applying the above methods in biomedical applications. My current projects include microscopic image analysis, image representation, video event detection, and generalized principal component analysis.

Tim Huang Research area: The novel approach of systems biology is being used to interrogate epigenetic alterations in cancer. Several microarray platforms have been developed for the whole genome-wide analysis of alterations in DNA methylation, histone, and chromatin-related proteins. Bioinformatics tools will be used to assess how these alterations contribute to transcriptional silencing in cancer.

F. Kay Huebner My laboratory is interested in defining genetic changes occurring in epithelial cancers; isolating genes involved in these genetic changes and determining their function in normal and cancer cells. We are currently focusing on two tumor suppressor genes located at chromosome fragile sites, as well as genes within the signal pathways of these fragile genes. Our longterm goal is to define roles for these suppressor gene pathways in cancer prevention and therapy.

John Hughes Current research investigations focus on the role that gravity has on cellular and viral functions. Studies are directed at understanding the molecular mechanisms involved with the cellular and gene expression changes that are induced by microgravity.

Ilya Ioschikhes  Research area: The major focus of my research is on bioinformatics analysis of gene regulation involving chromatin, transcription factor (TF) interactions with DNA, promoter analysis and other related topics. Methods involve sequence analysis and molecular structural modeling approaches. Our ultimate goal is molecular modeling of the promoter and transcription machinery taking into account all the aforementioned regulatory elements in their appropriate positions (also predicted by us in significant extent).

Samson Jacob Dr. Jacob?s research interests focus on two topics: (1) molecular mechanisms of induction of metallothionein, a protein that appears to protect cells/tissues from the deleterious effects of free radicals, UV radiation, stress, heavy toxic metals and some carcinogens (2) molecular mechanisms by which DNA methylation controls the expression of some genes, its biological significance and its role in some disease processes.

Lyn Jakeman Axonal regeneration is minimal following spinal cord injury due to the formation of an inhibitory environment at the site of damage. Rodent models and transplantation approaches are employed in the lab to examine the cellular and extracellular matrix composition in the injured cord and to test the efficacy of growth promoting strategies for regeneration.

Daniel Janies  Research area: It is through comparison that we identify functional regions of DNA, diagnose affected from unaffected individuals, or distinguish pathogenic from nonpathogenic organisms. To this end, the field of computational phylogenetics has much to offer for the understanding of complex and infectious diseases. An alignment of various organisms can identify regulatory regions conserved by evolution. Moreover, a phylogenetic tree search provides a complete accounting of candidate genes that changed between ancestors and descendants in patient populations or disease causing organisms.

Paul Janssen Our research focuses on the relaxation, contraction, and ion-homeostasis in the healthy and failing heart. We mainly use small cardiac muscle preparations to study contractile parameters, and assess different aspects of contraction and relaxation using state-of-the-art physiological techniques. Other projects include cardiac inotropic pharmacology, computer-modeling, adenovirus mediated modification of contraction.

Sissy Jhiang  Non-invasive imaging and targeted radionuclide therapy for cancer, signaling transduction in thyroid tumorigenesis, biological applications of atomic force microscopy and optical tweezers.

Kenneth Jones Dr. Jones is studying apoptosis, or programmed cell death, in cancer cells. Drug resistance in cancer cells may result from a decrease in the ability of a chemotherapeutic agent to induce apoptosis in cancer cells. Research is focused on a new agent that causes apoptosis and overcomes multi-drug resistance in leukemia cells.

Sheryl Justice Dr. Justice's laboratory uses uropathogenic Escherichia coli urinary tract infections as a model system to characterize consequences of host-pathogen interactions. Her laboratory seeks to characterize strategies employed by bacteria to evade the innate immune response as well as identify bacterial and host factors involved in the development of acute and chronic disease. Further elucidation of the molecular events that occur during this delicate interaction will lead to the development of better treatments and/or therapeutic agents to control bacterial infections.

Brian Kaspar Dr. Kaspar's laboratory studies the central nervous system with emphasis on neurodegenerative and neurological disorders. The laboratory has research interests in understanding and treating the underlying molecular and cellular mechanisms of neuronal cell loss in disease and injury to the brain and spinal cord. Research studies utilize neural stem cells, gene therapy vectors and animal models of neurodegenerative diseases to answer basic and applied biological questions.

Pravin Kaumaya The thrust of research in Dr. Kaumaya?s laboratory is in the general area of Peptide and Protein immunochemistry with special emphasis on modulation of the immune response and in the development of Synthetic Peptide Vaccines. We have developed strategies for the design of PEPTIDE VACCINES that can provide optimal B-cell, T helper cell and cytotoxic T cell responses.

Balveen Kaur The ultimate goal of my lab is to gain a detailed understanding of alterations induced in tumor micro-environment upon treatment with Oncolytic virus (OV), and to investigate the impact of these changes on OV mediated tumor Oncolysis. We are investigating OV induced changes in the tumor vasculature, invasion, and its ECM environment. Finally we are trying to translate these results into the design of smarter therapy

Samantha King We are interested in understanding how Streptococcus pneumoniae can colonize and persist in the human airway, and subsequently, on occasion, progress to a disease state. Specifically, we are investigating how bacterial deglycosylation of host glycoproteins and human cell surfaces contributes to interactions between S. pneumoniae and the human host.

Lawrence Kirschner  Research area: Dr. Kirschner?s laboratory is interested in studying the genetics and cell biology of endocrine tumorigenesis. Using transgenic mice as a model system, the lab studies the tissue-specific interactions of oncogenes and tumor suppressor genes to look for biochemical and genetic alterations that promote tumor formation. Because endocrine cells are so highly differentiated, this system will also allow us to investigate the balance between differentiation, proliteration, and homeostasis, both in vitro and in vivo.

Douglas Kniss The major focus of Dr. Kniss? laboratory is understanding the cellular and molecular pathophysiology of pregnancy complications involving the placenta. Specifically, they are examining the role of cyclooxygenase-2 (COX-2) induction by proinflammatory cytokines and growth factors that trigger the untimely onset of uterine contractions an cervical dilation. Inasmuch as premature labor is an inflammatory disease, they employ techniques and principles of inflammation biology in our studies. Most recently, they are investigating the interaction of the transcription factors NFkB and PPAR-g in driving the COX-2 gene leading to exuberant prostaglandin production using in vitro and in vivo model systems. In addition, they are embarking on a search for genetic polymorphisms in several target genes thought to be involved in some pregnancy complications. A smaller project in the laboratory involves the study of the effects of hyperglycemia (diabetes mellitus) on placental trophoblast function. A second emphasis of the Laboratory of Perinatal Research is in tissue engineering. This project is a multidisciplinary effort between Dr. Kniss? lab and the Departments of Chemical Engineering, Materials Science & Engineering and Pathology to study the influence of three-dimensional culture using a bioreactor to expand hematopoietic and tissue progenitor stem cells and examine their biology.

Sandra Kostyk  Research area: Research efforts focus on neurodegenerative disorders, neuroprotection and neurorecovery particularly related to Parkinson?s Disease, Huntington?s Disease and Spinal Cord Injury.

Laura Kresty Research area: Dr. Kresty?s research is focused on evaluating cancer chemopreventive agents utilizing cell culture, preclinical models and through conducting human clinical trials. The lab is focused on chemoprevention of aerodigestive tract cancers, particularly esophageal adenocarcinoma and the precursor lesion in Barrett?s esophagus. Surrogate endpoint biomarker development and assessment is an important component of Dr. Kresty?s research.

Tahsin Kurc Research area: Dr. Kurc?s areas of interest include high-performance and data-intensive computing. His research focuses on informatics systems to support management, querying, processing, and integration of information from disparate and heterogeneous biomedical data sources and scientific datasets. He also conducts research on methods for handling and analysis of large biomedical image datasets on high performance machines and parallel algorithms for scientific and engineering applications.

Jeffrey Kuret This laboratory employes molecular, cellular, and pharmacological methods to investigate Alzheimer's disease pathogenesis. Present work focuses on the formation of hallmark intracellular lesions (e.g. the formation of tau protein aggregates within neurofibrillary lesions). Our long term goals are to determine the mechanisms underlying neuritic lesion formation, including ther roles of postranslational modifications such as phosphorylation, and to develop small-molecule compounds capable of interfering with the process

JESSE KWIEK (Internal Medicine)  Prevention of HIV-1 mother-to-child transmission (MTCT) has been successfully implemented in the developed world, where the annual incidence of MTCT has been reduced to less that 2%; for example, in 2005, the USA reported 86 cases of perinatally acquired HIV.  However, in the developing world, HIV-1 MTCT remains a serious public health problem, with approximately 530,000 children newly HIV-1 infected in 2006 (http://www.unaids.org).  The Kwiek lab seeks to better understand the rmolecular biology and epidemiology of in utero HIV-1 MTCT.

William Lafuse Dr. Lafuse?s laboratory studies the interaction of Mycobacteria (M.avium and M. tuberculosis) with mouse and human macrophages. Current research investigates the effect of mycobacterial infection on macrophage cell signaling and transcriptional activation induced by IFN-gamma. The macrophage expression and function of iron transport proteins Nramp1 and Ferroportin I and a hormone, hepcidin, which regulates iron metabolism, is also being studied.

Michael Lairmore The study of regulatory and accessory proteins and virus encoded enzymes of complex retroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and human immunodeficiency virus (HIV) and have provided fundamental knowledge to define mechanisms of viral-induced transformation and basic paradigms of cell biology. My research is focused on using retrovirus models to elucidate basic cellular mechanisms governing transcriptional regulation of lymphocytes. This understanding will lead to new insights into the interface between pathogenic mechanisms of the virus during it?s replication and therapeutic modalities against retroviral-induced cancer.

Jas Lang Research comprises analysis of the gene alterations which occurs during the development of squamous cell carcinoma of the head and neck, and study of the aberrant function of the altered genes.

Larry Lasky  Research area: The laboratory is devoted to expansion of hematopoietic stem and progenitor cells for a variety of uses. Specific projects include enhancement of a 3D culture method developed previously, genetic control of apoptosis and self-renewal in these cells, and development of a 3D computer-controlled perfusion bioreactor.

Beth Lee The research emphasis in Dr. Lee's laboratory is the study of kidney and bone cell biology. A major focus of the lab is research into mechanisms by which kidney epithelia preserve their complement of messenger RNAs during ischemic cell stress. A second major focus is aimed at studying how actin-binding proteins, particularly myosins and tropomyosins, regulate morphology and activity of a bone-degrading cell, the osteoclast.

Stan Lemeshow Dr. Lemeshow?s research has concerned statistical modeling in medical and epidemiologic studies. An example has been his work in developing severity of illness models for ICU patients. Dr. Lemeshow has also been interested in appropriate modeling of data from complex sample surveys.

Gustavo Leone 

n tMy lab is currently studying the role of the Ras pathway in coordinating cell growth and cell death signals elicited by the E2F and Myc transcription programs.

Uncontrolled cell proliferation is the hallmark of cancer, and tumor cells have typically acquired damage to genes that directly regulate their cell cycles. Mounting evidence implicates the E2F transcription family as an important regulator of the cell cycle. It is now clear that the disruption of various components of the pathway controlling E2F accumulation, either the activation of positive acting components such as Ras, Myc, G1 cyclins and their kinase subunits (CDKs), or the inactivation of negative components such as Rb, p53 and the CDK inhibitors (INK4 genes), can lead to the loss of cell growth control underlying the development of various forms of human cancer.

Mammalian E2F is composed of a family of heterodimers encoded by six distinct genes. Our recent work has highlighted the roles of the E2F3 and E2F1 gene products as key regulators of cellular proliferation and apoptosis, respectively. The focus in my lab will be threefold:

First, using in vivo KO mouse models we will investigate the role of the E2F3 gene locus in the control of the cell cycle and cellular proliferation. The E2F3 locus encodes two distinct gene products, the E2F3a and E2F3b proteins. Particularly important is the observation that this novel E2F3b gene product is the predominant partner for the Rb tumor suppressor in non-proliferating cells. We will investigate the in vivo role of E2F3a in promoting cell cycle progression and the potential function of the novel E2F3b protein as a tumor suppressor.

Second, we will take advantage of a recombinant adenovirus expression system and of fibroblasts deficient for various cell cycle regulators in order to elucidate the mechanism by which E2F1 elicits an apoptotic signal. In addition we will employ fibroblasts deficient for E2F1, E2F2 and E2F3a/b in order to determine the relative contributions of these family members towards the E2F apoptotic program and to identify, using gene chip expression arrays, novel E2F targets important for executing the cell death program.

Finally, our lab is interested in determining how signal transduction pathways important for normal cellular proliferation may intersect and modulate E2F- and Myc-mediated apoptotic signals. In particular, our recent experiments have elucidated a Ras dependent pathway important for countering an E2F1- or Myc-mediated death signal, but the identity and regulation of the key activities important for coordinating these cell survival and cell death signals have yet to be determined.

Through these studies we will not only further our molecular understanding of the control of cell growth and apoptosis, but we hope to also achieve an understanding of how these two fundamental processes are coordinated during the cell cycle to regulate normal proliferation, the disruption of which often leads to the development of human cancers.

Gene Leys Molecular epidemiology of polymicrobial infections, using oral diseases as a model. Genetic variation in oral pathogens and the relation of variants to disease. Interactions of complex biofilms with host tissues.

Chien-liang Lin Dr. Lin?s laboratory utilizes a combination of cellular, molecular, biochemical and animal model approaches to investigate molecular mechanisms underlying neurodegenerative diseases, primarily Alzheimer?s disease and ALS. Three projects are currently under investigation: role of RNA oxidation in the diseases, mechanism of glutamate transporter alterations in the diseases, and investigation of a novel factor that can reduce oxidative damage

HUEY-JEN LIN (Allied Medical Professions)  My main research interest is to study the molecular pathogenesis of breast cancer.  Breast carcinoma is the most common and a major cause of death in women worldwide.  Majority of mammary tumor arises from the epithelial lining glands and ducts, but unlikely the stroma adjacent to epithelial lining.  Stroma comprises bibroblasts, endothelial cells, macrophages, lymphocytes, and adiopocytes.  Normal mammary stroma has a major role in supporting the normal functions and regulation of physiological processes in the breast.  In contrast, aberrant mammary stroma may not be directly tumorgenic, but somehow lead to breast cancer.

Recent studies have identified fibroblasts and other cell types within the tumor-microenvironment (the stromal compartment consisting of both the connective tissue cells and their soluble factors) as being critical for tumorigenesis.   Tumor epithelial cells commonly harbor “silenced” tumor suppressor genes, partly due to DNA hypermethylation.   To date, the mechanistic cause(s) leading to DNA hypermethylation and gene silencing remains unresolved.   Despite that the studies pertaining to how tumor-microenvironment promotes malignancy are beginning to emerge, whether or not it is responsible for causing DNA hypermethylation in breast epithelial cells remains unknown.   We hypothesize that the tumor-microenvironment confers the non-cancerous epithelial cells (comparable to the normal epithelial cells adjacent to breast tumors) into a malignant stage, in part by augmenting DNA methylation.   Specifically, we aim to study the influence of cancer-associated stromal fibroblasts on two interrelated non-cancerous breast epithelial cells (MCF10A and HMEC) in laboratory cultivation system.   Our preliminary findings have demonstrated novel DNA methylation and silencing of the CST6 gene, and provided a promising avenue to explore six additional genes whose hypermethylation was concordantly induced from cancer-associated fibroblasts.   Such phenomenon was not reported in any other human cancer.   If proven, this finding is the first proof-of-principle demonstrating that breast cancer-associated fibroblasts can induce DNA hypermethylation in noncancerous mammary epithelial cells.   Moreover, we will carry out a global methylation microarray profiling to identify additional genes whose hypermethylation is similarly induced.   Altogether, these loci potentially comprise diagnostic biomarker genes.   In summary, this study will advance our understanding about how the tumor-microenvironment conveys DNA methylation to promote breast tumorigenesis, and will pioneer a new breast cancer research arena. 

Jiayuh Lin Dr.Lin's laboratory studies the molecular mechanisms of Signal Transducer and Activator of Transcription 3 (STAT3) pathway in human cancers. Constitutive activation of Stat3 is frequently detected in many types of human cancers. We are identifying and studying the novel Stat3-regulated genes and how they may function in Stat3-mediated cell survival, proliferation and tumor angiogenesis in cancer cells. The laboratory is also developing novel structure-based design of Stat3-selective small molecule inhibitors as well as short interfering RNA to selectively inhibit Stat3 oncogenic pathway in cancer cells as a potential cancer therapeutic approach

Alan Litsky Dr. Litsky?s research interests focus on endoprosthesis fixation, novel biomaterials, and the biomechanics of fracture fixation. A major research program in his laboratory has been the evaluation of a new reduced-modulus bone cement formulation. Other major research efforts include the development of a bioceramic-metallic composite with interpenetrating structures to achieve solid prosthesis fixation without the debonding problem found with current ceramic-coated implants, an exploration of the applications of shape-memory alloy for fracture fixation, and measurement of the micromotion between the components of total joint prostheses. More clinical projects include several studies of the rigidity of various fracture fixation devices, comparison of various surgical techniques used for patellar-mechanism realignment, and a comparison of the elastic, viscoelastic, and fatigue properties of different acrylic cement formulations.

Yusen Liu Research area: Research in Dr. Liu?s laboratory focuses on the signal transduction pathways that regulate the cellular responses to extracellular stimuli. A major emphasis in the laboratory is to investigate the role of MAP kinase phosphatases in the regulation of inflammatory cytokine biosynthesis in macrophages during bacterial infection. Additional studies include investigations into the basic mechanisms of aging and the molecular mechanisms via which triptolide induces apoptosis in a variety of cancer cells.

Amy Lovett-Racke My laboratory studies the pathophysiology of multiple sclerosis. The primary focus of the laboratory is characterizing encephalitogenic T cells and developing therapeutics that target these cells. Experimental autoimmunie encephalomyelitis, a mouse model for multiple sclerosis, is studied, as well as patient T cells.

Jiyan Ma Research area: Current research interest is to understand the pathogenic mechanism of neurodegenerative diseases, with particular interest in prion disease. We are using various molecular biology and cell biology techniques, including transgenic mice, to study how a normal protein becomes neurotoxic. We are also interested in protein folding, protein quality control mechanism, changing in protein folding and the quality control mechanism during aging, and protein conformation dependent inheritance.

Susan Mallery Research area: Dr. Mallery's laboratory is focused on cancer cell biochemistry. Specific projects include investigation of the roles of oxidant stress and carcinogen metabolism on the initiation of oral cancer. This project involves functional enzymatic and molecular analyses using in vitro cultured human cells as well as animal models. Dr. Mallery's laboratory also studies the contribution of cytokines and aberrant cell signalling in the pathogenesis of AIDS-related Kaposi's sarcoma, also using cultured human AIDS-KS cells and animal models. Recent collaborations with a pharmaceutical chemist, Dr. Steve Schendenman of the University of Michigan, has permitted Dr. Mallery's laboratory to begin translationally applicable investigations, using controlled-release biodegradable devices, for the delivery of chemotherapeutic, and most recently, angiostatic, agents.

Stuart Mangel Dr. Mangel's lab uses the vertebrate retina, which is part of the brain, as a model system for understanding brain function and dysfunction due to its easy accessibility and well-characterized inputs. His laboratory is currently pursuing two research objectives using electrophysiological, neurochemical, anatomical, and comutational techniques. First, they are studying how a circadian (24-hour) clock in the retina modulates cellular processes and chemical and electrical synaptic transmission and how disruption of this circadian system mediates retinal diseases. Second, they are studying the cellular, subcellular (e.g. transporters), developmental, and neural network mechanisms that underlie how the retina responds to moving objects.

Jeanette Marketon My lab is interested in modulation of nuclear hormone receptors. Receptors of this family plan a critical role in homeostasis and dysregulation in their signaling has been shown to be involved in many diseases. Specifically, we are interested in investigating the precise molecular mechanism by which an agent (environmental or infectious) or a disease state may modify glucocorticoid receptor signaling.

Clay Marsh Dr. Marsh?s research involves understanding the biochemical pathways that regulate the survival and differentiation of blood monocytes and tissue machrophages. Dr. Marsh is also interested in understanding the role and regulation of phosphatases and kinases in growth factor signal transduction in blood monocytes and tissue macrophages and applying these to human disease. His laboratory recently uncovered a novel mechanism by which monocytes and macrophages regulate angiogenesis, a finding they are pursuing in human disease, including lung fibrosis and breast cancer metastases.

Paul Martin Research area: The Martin lab is interested in understanding the role of glycosylation in the neuromuscular development and disease. The lab utilizes transgenic and gene knockout mice, as well as gene therapy approaches, to identify functional roles for glycans and to design therapies for muscular dystrophy. The lab also studies roles for glycosylation in brain development and neurodegenerative diseases, including Alzheimer?s disease.

KEVIN MASON (Pediatrics)  Nontypeable Haemophilus influenzae (NTHi) is a common member of the host microflora (a commensal) and yet predominates in diseases of both the upper and lower respiratory tracts (opportunistic pathogen).  We hypothesize that the pathogenic potential of NTHi is dictated by its ability to resist immune-mediated clearance mechaniisms and specifically, killing by host antimicrobial peptides (APs).  We ar currently investigating a mechanism by which NTHi sense and transport APs for proteolytic cleavage, in parallel with increased potassium uptake, thus supporting a dual molecular mechanism that promotes bacterial survival and establishment of disease.

Velimir Matkovic Primary prevention of osteoporosis. Determinants of peak bone mass. Calcium metabolism and requirements throughout life. Bone loss and fractures.

Kim McBride Research area: My primary research interest is the dissection of complex genetic diseases, focused on a group of congenital heart defects called left ventricular outflow tract obstruction malformations, which include bicuspid aortic valve, congenital aortic valve stenosis, coarctation of the aorta, and hypoplastic left heart syndrome. I am using a variety of gene mapping techniques, including linkage analysis and large-scale family-based associated studies, to uncover the genetic basis of this group of disorders. Candidate genes will be further studied by a variety of molecular genetic and biology approaches.

Douglas McCarty Research area: We have developed a self-complementary derivative of recombinant adeno-associated virus (rAAV) for use as a high-efficiency gene delivery vector for anti-oxidant gene therapy to protect against ischemia-reperfusion injury in liver. We have also used the unique molecular properties of this vector genome to characterize the DNA recombination mechanisms that generate circular and concateremeric rAAV episomes. We are currently extending these studies to the mechanism for r AAV DNA integrations into the host chromosome and the potential for insertional mutagenesis.

Bradford McGwire Research area: Dr. McGwire?s research focuses on the mechanisms by which the related pathogenic protozoa Leishmania and trypanosomes (T. cruzi and T. brucei) establish and maintain infection in their mammalian hosts. Current work focuses on the recognition of and invasion of extracellular matrix (ECM) proteins during early stages of infection as well as the functional role of parasite surface metalloproteases in evasion of innate antimicrobial factors such as antimicrobial peptides (AMPs).

Kirk McHugh  Research area: The research efforts in my laboratory rely upon an integrated scientific approach that is designed to identify the genetic pathways responsible for the ontogenesis and pathogenesis of smooth muscle tissues. The dysregulation of smooth muscle differentiation represents an important clinical challenge in a variety of diseases and birth defects including atherosclerosis, asthma, Crohn?s disease, ulcerative colitis, interstitial cystitis, the neoplastic transformation of smooth muscle cells, lymphangioleimyomatosis, and Hirschsprung?s disease. Using a wide range of molecular techniques in conjunction with clinical collaborations, we have determined that serum response factor (SRF), myocyte enhancement factor 2 (MEF2), and NK-2 homeobox gene, and several, as yet, unidentified factors all play an overlapping role in modulating smooth muscle cell differentiation during normal development and pathogenesis.

Dana McTigue Research area: My research focuses on the effects of spinal cord injury on oligodendrocytes and oligodendrocyte progenitors found within the adult spinal cord. We are examining factors that may contribute to oligodendrocyte loss and demyelination as well as potential therapeutic agents that may lead to improved oligodendrocyte survival, enhanced myelination and functional improvements after spinal cord injury.

Nicanor Moldovan Cellular mechanisms of angiogenesis, focusing on the role of monocytes/macrophages. In this context, the laboratory has developed a new model of intercellular cooperation, based on the effect of degradation of the extracellular matrix (?tunneling?) by one cell type, on the migration behavior of another cell type. Emphasis is put on the tissular recruitment and insemination of circulating precursor endothelial cells in adult animals. By extension, the tunneling model is used in the design and implementation of artificial capillaries at the interface between inorganic materials and biological tissues. This second project is part of the lab?s interest in novel models and techniques useful for cardiovascular biomedical engineering.

Federica Montanaro The Montanaro lab is interested in understanding the molecular mechanisms that underlie muscle fiber degeneration and regeneration in muscular dystrophy and in developing cell-based therapy approaches for this group of diseases. On one hand, the lab uses in vitro models of muscle development, in vivo models of muscular dystrophy, RNA interference, and gene chip analysis to identify cellular signaling pathways that are altered in muscular dystrophy. On the other hand, fluorescence activated cell sorting, immunophenotyping, and cell culture are used to isolate and characterize populations of adult stem cells that have the potential to participate in muscle fiber regeneration upon transplantation into mouse models of muscular dystrophy.

Robert Munson Dr. Munson?s research centers on the understanding of gram-negative bacterial pathogenesis, working primarily on virulence determinants of Haemophilus ducreyi and Haemophilus influenzae. In addition, they have programs in bacterial genomes and global regulation of bacterial gene expression.

Raj Muthusamy Dr. Muthusamy?s laboratory is interested in regulation of lymphocyte development and function using transgenic and gene targeted mouse models.

Kirk Mykytyn Research area: Research in Dr. Mykytyn?s lab focuses on the pathophysiology of complex diseases, using a Mendelian disorder that displays complex phenotypes as a model. Bardet-Biedl syndrome (BBS) is a heterogeneous genetic disorder with the primary features of obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism. Patients with BBS are also at increase risk for diabetes mellitus, hypertension and congenital heart disease. We have developed mouse models for this disorder that will provide insights into the mechanisms underlying the BBS phenotypes.

Patrick Nana-Sinkam Our laboratory focuses on three areas of translational research in lung cancer. First is determining the mechanisms by which eicosanoids affect lung tumorigenesis. Secondly, identifying new signaling pathways between the epithelium and endothelium in lung tumorigenesis. Third, we are interested in identifying new biomarkers in lung cancer through the use of microarray, SNP and microRNA platforms.

Norton Neff Research is focused on neurodegenerative disorders, primarily Alzheimer?s and Parkinson?s diseases and aging. The mechanism for neurotropic factor correction of degenerative processes is under study. In addition, preservation and stabilization of enzymes that are essential for neurotransmitter synthesis in degenerating neurons are an important part of the research activity. Animal models of neurodegenerative diseases, tissue culture systems and isolated brain structures are utilized for study.

Leif Nelin The research focus in my laboratory is on the elucidation of the functional and mechanistic aspects of cellular uptake of L-arginine by the cationic amino acid transporters (CAT) and the role of CAT activities and expression in regulation of nitric oxide (NO) production in the lung. Experiments are carried out in cell culture systems and animal models using pharmacological and genetic manipulations with experimental end-points ranging from biochemical assays, protein and mRNA assays, to functional and physiological measurements. The long-term goals of these studies are to develop therapies that increase NO production by facilitating CAT-mediated L-arg uptake in pulmonary hypertensive diseases, and that decrease NO production by inhibiting CAT-mediated L-arg uptake in inflammatory lung diseases.

Ichiko Nishijima Research area: Our primary research interest is to identify and characterize the genetic factors causing human developmental disorders. Autism is a complex developmental disorder marked by social and cognitive abnormalities. We have generated mouse models of autism and other developmental disorders and aim to understand what causes these diseases,

John Oberdick In our lab we study the mouse cerebellum as a model for identifying molecular and genetic mechanisms controlling development and function in the brain. The two main projects are to identify 1) the genetic regulators of boundary formation in the cerebellum that dictate the early ?hard-wiring? of the cerebellum and 2) the mechanisms and function of selective mRNA utilization in dendrites (the receiving end of neurons) as it relates to synaptic plasticity (learning and memory). Both of these projects center around the study of a Purkinje cell ?specific G-protein modulator called L7/Pcp-2; these studies have allowed us to link genetic control factors such as Engrailed-2, Hox proteins, and RORa (stagger gene) to a multi-functional signaling pathway that has a direct functional read-out in terms of measurable effects on motor performance.

Tatiana Oberyszyn Dr. Oberyszyn is interested in understanding the function of biological mediators including prostaglandins, cytokines and reactive oxygen intermediates that play a role in ultraviolet light induced damage to the skin which ultimately leads to the development of skin cancer. She is also interested in the wound healing process, developmental gene expression in the skin and how it relates to the carcinogenic process.

Karl Obrietan Research area: Dr. Obrietan?s laboratory utilizes a combination of cellular, molecular and behavioral approaches to examine the second messenger signaling and transcriptional pathways that regulate biological timing. A second area of research examines the cellular signaling events that couple seizures to synaptic reorganization in the hippocampus.

Michael Oglesbee Cellular heat shock proteins play fundamental roles in protecting cells from stress and modulating innate and adaptive immune responses. My laboratory has shown that heat shock proteins also stimulate gene expression and replication of negative strand RNA viruses such as measles, canine distemper, and rabies virus. Current focus examines mechanisms by which heat shock proteins regulate viral gene expression and the impact upon viral neurovirulence.

Michael Ostrowski 

The Ostrowski lab has a long-standing interest in understanding how signaling pathways elicit selective, persistent changes in gene transcription in mammalian cells. We have three ongoing projects funded by NIH ( 5R01CA053271-13, 2R01AR044719-05A1; 1P01CA097189, see: http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen).  One project is centered on the ras/Erk/ets signaling pathway in cancer cells (abnormal signaling project) and one on the rac/p38 MAP kinase/microphthalmia transcription factor pathway during normal bone development and bone remodeling that occurs throughout life (normal signaling project), and a new project studies the role of the ras/ets pathway in the breast tumor microenvironment.

1. Abnormal Signaling: Persistent Activation of Gene Expression by the ras/ets Signaling Pathway in Inflammation and Tumorigenesis

2. Normal Signaling: The Role of the microphthalmia Transcription Factor in Osteoclast Differentiation

3. Genetic Analysis of the Tumor Microenvironment in Breast Cancer Progression.

As part of a multidisciplinary collaboration that includes faculty members in 4 colleges and 7 departments at OSU, we are taking a genetic approach to study the effect of gene action from the tumor microenvironment on breast cancer progression.&