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Inflammatory diseases and innate immune signaling pathways

Responses of cells to extracellular matrix (ECM). ECM is fundamental to cell interactions in the tissues of metazoan organisms.

Biomimetic tissue engineering; innovative biomaterials and drug delivery vehicles for functional tissue regeneration and cancer therapy; control of stem cell differentiation

Enzyme reaction mechanisms; Protein-protein interactions; Protein oxidation; Mass spectrometry

Biocompatibility of implants, human vascular grafts, immune responses to foreign materials, phagocytosis, inflammation

HIV-1 drug resistance to nucleoside and chemokine analogs; HIV-1 evolution and emergence of drug resistance in Africa.

Mechanistic enzymology and drug discovery focusing on inhibitors of DNA replication and ATP-dependent enzymes

Structure function studies of Class A beta-lactamases. Understanding enzymological factors that permit the successful evolution of beta-lactamases in the clinic. Development of immunological tools to study beta-lactamase expression in enteric bacilli.

CD4+ T cells,CD8+ T cells,gamma delta T cells,tuberculosis,cytokines,antigen processing,anti-microbial immunity,HIV-1,pulmonary host defense

Physiology of ion-transport processes involved in the regulation of intracellular pH

Receptor protein tyrosine phosphatases, cell adhesion, and signal transduction; PTPs in adherens junctions and desmosomes.

Fundamental biological mechanisms guiding the generation of functional neuronal classes

Metabolic regulation, ketone body metabolism, design and testing of synthetic nutrients, ethanol metabolism, lipogenesis

Molecular Biophysics of small GTPase-protein interactions in neuronal cell signaling. We use molecular biology, NMR and X-ray spectroscopy as well as thermodynamic measurements to determine the basic mechanisms by which proteins transmit signals in cells. Principal project: The plexin transmembrane receptor in axon guidance.

Developmental and cell biology and biochemistry of muscle, cartilage, bone, skin and connective tissue, with emphasis on how stem cells differentiate under conditions of tissue-engineered regeneration

Enzyme mechanisms, Raman spectroscopy, beta-lactamases and ribozymes, physical biochemistry

Protein Structure / Function: Digestive, Liver and Epithelial, Endocrine, Metabolic Disorders, Cancer, Diabetes

Systems Integrated Physiology: Muscle, Heart, Metabolic Disorders, Hypertension, Diabetes, Cardiovascular Disease

Aging; cell biology; dementia; degenerative disease; neuroscience; prion disease; protein chemistry

Neural networks, electrophysiology, modeling, Aplysia, biomechanics, feeding behavior.

The molecular changes in the pancreas of animal models that are either resistant or sensitive to obesity in response to environmental stresses such as caffeine and a high-fat diet.

Inflammation in the CF lung and therapeutics directed at it; nonviral gene transfer to airway epithelium

Bacterial molecular genetics; biochemistry and cell biology; formation of the division of septum and related cell cycle events

Understanding the structural organization requirements by multiple protein assemblies to facilitate biological function

Mechanisms of neuronal gene expression, cholinergic and serotonergic transmitter systems.

Lipocalin 24p3 and its role in apoptosis, iron transport, innate immmunity, and myeloproliferative disease

Steroid hormone action; programmed cell death; apoptosis.

Signal transduction involving receptors for extracellular ATP; inflammatory signal transduction mechanisms; mechanisms of nucleotide release and extracellular metabolism.

Magnetic resonance imaging, flow visualization, interventional MRI, rapid MR imaging, MR vessel wall imaging

Neural engineering, neural prostheses, magnetic and electric stimulation of the nervous system, electrophysiology of epilepsy, computational neuroscience.

Signaling pathways and mechanics of cancer cell chemotaxis; cell biology of chemotaxis in the model organism Dictyostelium discoideum.

Development of statistical methods for analyzing family and pedigree data for the identification of genes that cause disease, implementing them in computer programs, and applying them in collaborative research with others who collect family data.

Minimally invasive methods of cancer treatment including: ultrasound-modulated, image-guided drug delivery, thermosensitizers for focused hyperthermia, and vasomodulation for improved local ablation and treatment follow-up

T-lymphocyte tolerance, transplantation immunology

Regulation of gene expression and phenotypic switching in vascular smooth muscle; role of programmed cell death and chamber-specific gene expression during heart development

Protein structure and dynamics; NMR techniques; molecular modeling of glycoproteins and mucins

Transgenic mice and carcinogenesis, retroviral gene therapy, DNA repair, hematopoietic stem cells

Osteoporosis, loosening of orthopaedic implants, cytokines, osteoblasts, osteoclasts, bone resorption, cell-cell interactions, osteosarcoma, signal transduction

Neural engineering and neural prosthesis development with a focus on understanding systems-level neurophysiology and neural control of pelvic functions

Developmental neurobiology, sensory neurons and pain after inflammation, stroke neuroprotection

Analysis of mechanisms regulating inflammatory gene expression in mononuclear phagocytes. Analysis of stimulus-dependent control of chemokine and cytokine mRNA stability.

Immunology, major histocompatibility complex (MHC) molecules, antigen processing, function of antigen presenting cells and T cells, Toll-like receptors, vaccine adjuvants, Cell Biology, phagocytosis, endocytosis, subcellular fractionation, Infectious Disease, mycobacteria, tuberculosis

Molecular recognition and catalysis by the ribonuclease P: A ribonucleoprotein enzyme, and analysis of phosphoryl transfer mechanisms using kinetic isotope effects

Epigenetic regulation of chromatin structure and transcription, histone modifying enzymes, Polycomb silencing, genetic control of lifespan and aging

Understanding the nature of cellular quiescence, the counterpart to proliferation; the role of MyoD in the biology of satellite cells, the adult stem cells of skeletal muscle; and the epigenetic specification of melanoma

Arginine metabolism, gene regulation, viral receptors and gene therapy

inflammation biology, free radicals and oxidation chemistry, internal medicine, endocrinology

Modulation of ion channels, signaling pathways and neuronal networks for mouse physiology and behavior

Mechanical Properties of Cancellous Bone and Bone Adaptation and Cancellous Bone Mechanics

Tumor Immunology; Intravital two-photon laser scanning microscopy; T cell and chemokine receptor biology; Cellular trafficking, migration and interaction in inflammation, cancer and auto-immunity

Genetics of complex diseases in humans

Lifestyle, environmental, and occupational factors and their impact on reproductive and perinatal health

Transcriptional mechanisms governing cellular differentiation and function

Single molecule enzymology (RNA helicases) & single molecule studies of ribonucleoprotein machinery (HCV replication and pre-mRNA splicing)

Voltage dependent ion channels, electrophysiology, patch clamp, Ca2+ currents, K+ currents

Control of Gene Expression in HIV

Regulatory interactions in development of the nervous system, neurotransmitter phenotypes, neural growth factors.

Immunoregulatory mechanisms of pathogenesis; acquired resistance to infection; malaria

Hormonal control of mammary gland development and construction of transgenic mouse models of breast cancer; functional genomics of mammary gland development and cancer.

T cell differentiation, Malaria Schistosomiasis, Filariasis Neonatal immunity, IgE regulation Mechanisms of acquired immunity

Mechanics and control of human movement

Cerebral blood flow, cerebral ischemia, blood-brain barrier

Alzheimer's Disease; Genomic Imprinting and Epigenetics; Yeast Artificial Chromosome Transgenic Mice; Models of Human Disease; Epigenetic Gene Regulation; Developmental Control of Epigenetics

Formation of neural circuits, growth cone guidance, synapse plasticity, activity dependant processes.

Nerve growth factor, protein kinases, MAP 2 kinase, Alzheimer's disease.

Mechanisms of immune deficiency and immune restoration in HIV infection

Immune regulation, with targeted interest in (i) IBD in the intestine: Role of the mucosal T lymphocyte and epithelial cell, (ii) Intestinal permeability in HIV infection, and (iii) Link between chronic inflammation and colorectal cancer

Signal transduction in innate and adaptive immunity

Alternative RNA processing and its role in cancer development

Molecular mechanisms of vitamin D- and nuclear receptor-mediated gene expression.

Mg2+ homeostasis; Structure of Mg2+ channels, esp. the CorA superfamily of channels; Role of Mg2+ in Salmonella pathogenesis

Etiology, treatment and prevention of cancer: signal transduction pathways that regulate normal cell growth; molecular prevention

Biomaterials. Biopolymers, bio-synthetic surfactants, polymer surface modification for implants and sensors, protein-surface interactions by AFM.

Colon cancer genetics

Interaction between electric fields and the Nervous System, specifically Deep Brain Stimulation (DBS)

Human endothelial cell, monocyte/macrophage and leukocyte function. Inflammatory signaling molecules, lipid mediators and intercellular adhesion molecules. Enzymes that make and degrade Platelet-activating Factor, phospholipid oxidation and eicosanoid function.

Mechanism and regulation of eukaryotic protein biosynthesis

Enzymatic reaction mechanisms involved in intracellular sulfhydryl homeostasis, drug and xenobiotic metabolism, and cancer chemotherapy.

Developmental neurobiology, glial function, CNS pattern formation

Apoptotic (caspase activation and signaling) and inflammatory mechanisms in the development of diabetic retinopathy, identifying new drugs and treatment strategies using retinal cells and animal models of diabetic retinopathy

Development of the mammalian gonad

Molecular mechanisms of protein aging, oxidative stress, complications of diabetes and aging, cataractogenesis, microbial enzyme technology

Comparative Mapping and Mouse Models of Human Disease; Networks of Control of Gene Expression; Genetic and Phenotypic Dissection of Complex Traits Using Mouse Genomics

Innate immunity and liver disease, ethanol and signal transduction

Host-mycobacterial interactions; virulence factors of Mycobacterium tuberculosis; antibiotic resistance and cell biology of mycobacteria

RNA processing and transcription in nematodes. Homologous cell free systems are used to dissect in detail the mechanisms of cis- and trans-splicing as well as the transcription of UsnRNA genes

Mechanisms of action and biological functions of nuclear hormone receptors

Mapping the Visual Transduction System

Murine models of immunoparasitology, including ocular immunology, corneal pathology, onchocercal skin disease and allergic asthma

Motor function restoration with neural prostheses, control of orthotic and prosthetic systems.

myocardial ischemia, vascular biology, cardiac critical care

multiple sclerosis, neuroimmunology

Mechanical performance of orthopaedic total joint replacements through fundamental materials studies and implant retrieval analysis; skeletal fragility of bone tissue (damage accumulation and repair); design and manufacture of resorbable polymeric scaffolds for bone tissue regeneration and repair.

The application of advanced optics and photonics technologies for in vivo microscopic imaging and characterization of biological tissues, with particular emphasis on early cancer detection and phenotyping and morphometry in early cardiac development using Optical Coherence Tomography.

The role of lipid oxidation in disease, develop new diagnostic tools for identifying individuals at risk and assessing the efficacy of therapeutic interventions, provide a molecular basis for the design of new drugs and strategies

Drosophila molecular genetics; Post-transcriptional control of cell fate determination; Alternative RNA splicing

The goal of our research is to understand the role of enzymes that mark chromatin by post-translational modification and how deregulation of these enzymes contributes to the development of cancer.

Protein modification by lipid-derived products of oxidative stress in degenerative disease; mechanism-based inhibitors of copper-containing amine oxidases

Genomics of cancer and other human diseases with underlying defects in chromatin structure and function

Molecular Virology, Mechanism of Interferon Action, Recombinant DNA Technology, Genetic Regulation of Hypertension

Role of glial cells in development and regeneration of neural circuits, nerve regeneration, glia, axon guidance

thrombosis, athersclerosis, angiogenesis

Aging, Alzheimer disease, cell cycle control, cytoskeletal organization, neurodegeneration, oxidative stress

Endocrine, Brain and Nervous System, Heart, Metabolic Disorders, Hypertension, Pulmonary Disease, Cardiovascular Disease

Signaling by Interferons, Growth Factors and Cytokines; Genetic Instability and p53

Synaptic Physiology, hippocampus, olfactory bulb, Computational Neuroscience.

Understanding signaling pathways that determine early pattern formation of vertebrate embryogenesis, particularly the molecular mechanisms of the Wnt signaling pathway

Rehabilitation engineering, neural control of motion, lower- extremity neuroprostheses, orthopaedic biomechanics and prosthetic/orthotic design

Autoimmunity, Multiple Sclerosis

Function of human snRNAs, functional analysis of large non-coding RNAs

The overall goal of my research is to elucidate the molecular intricacies of enzyme mechanism and receptor activation. Our structural biology projects range from guanylyl cyclases (blood pressure, vision, and bone growth) to beta-lactamases (largely responsible for the current epidemic antibiotic resistance).

Biomechanics and motor control of human movement; joint mechanics and injury; neural prostheses; computational modeling

Identifying novel genetic alterations, such as somatic mutations, gene amplifications and deletions, which alter critical gene functions involved in development of colon and gastric cancers

Molecular mechanisms governing cell migration and proliferation, experimental therapy of cancer metastasis using tumor-targeting peptides.

Structural mechanisms of human diseases; Transcriptional deregulation and protein misfolding with applications to diabetes and disorders of sexual development

Biomedical image processing; digital processing and quantitative image quality of X-ray fluoroscopy images; interventional MRI.

Mechanism and regulation of pre-mRNA splicing in S. pombe

structures and mechanisms involved in protein mis-folding and amyloid formation.