The work in our laboratory is focused on understanding the molecular pathogenesis of Kaposi’s sarcoma-associated herpesvirus (KSHV), an oncogenic human virus. KSHV is associated with several types of cancer in the human population. We study the effect of KSHV viral proteins on cell proliferation, transformation, apoptosis, angiogenesis and cell signal transduction pathways. We also study viral transcription factors, viral replication, and the interactions of KSHV with the human innate immune system. Additionally, we are developing drug therapies that curb viral replication and target tumor cells.
Our research centers on understanding the
molecular basis of human carcinogenesis. In particular, a major focus of our studies is the Ras oncogene and Ras-mediated signal transduction. The goals of our studies include the delineation of the complex components of Ras signaling and the development of anti-Ras inhibitors for cancer treatment. Another major focus of our studies involves our validation of the involvement of Ras-related small GTPases (e.g., Ral, Rho) in cancer. We utilize a broad spectrum of technical approaches that include cell culture and mouse models, C. elegans, protein crystallography, microarray gene expression or proteomics analyses, and clinical trial analyses.
We study how mammalian cells activate the programmed cell death pathway and die by apoptosis. We have focused our work on identifying unique mechanisms by which this pathway is regulated in postmitotic cells such as neurons, cardiomyocytes, and myotubes, as well as cancer, senescent, and stem cells. Excessive cell death is seen in many pathological conditions such as after stroke, neurodegeneration or cardiovascular diseases. In contrast, reduced cell death is a hallmark of cancers. Therefore, discovering the mechanism by which mammalian cells regulate cell death has significant therapeutic implications.
As the Director of the UNC Kidney Center, the scope of Dr. Falk's research interests spans many disciplines, including
molecular biology, immunology, genetics, pathology, cell biology, protein chemistry, epidemiology, pharmacokinetics and biostatistics. Dr. Falk is recognized world wide as a leader in research on kidney diseases related to autoimmune responses. He works closely with the basic research scientists within the UNC Kidney Center, including Dr. Gloria Preston, thus this research program provides an environment for Translational Research within the UNC Kidney Center.
Dr. Gilmore’s research group is applying state-of–the-art magnetic resonance imaging and image analysis techniques to study human brain development in 0-6 year olds, with a focus on cortical gray and white matter development. Studies include normally developing children, twins, and children at high risk for schizophrenia and bipolar illness. We are beginning to study the contributions of specific genes of risk to brain development in humans. A collaborative study with the Harlow Primate Lab at the University of Wisconsin is using imaging to study brain development in Rhesus monkeys, and the impact of prenatal exposure to maternal infection on brain development.
Dr. Gulley's research is on Epstein-Barr virus (EBV)-related malignancies. Molecular and immunohistochemical techniques are used to characterize infected tissues. We validate new assays to help diagnose and monitor affected patients.
Research in my lab focuses on the mechanisms by which exposure to air pollutants can enhance the susceptibility to and the severity of respiratory virus infections. Specifically, we are examining the effects of air pollutants such as diesel exhaust and cigarette smoke on influenza virus infections, using several in vitro models of the respiratory epithelium. In
collaboration with physicians from the Department of Pediatrics, we are also translating these studies into humans in vivo.
My research interests and diagnostic responsibilities center around nephropathology and immunopathology. My laboratory carries out basic, translational and clinicopathologic research on kidney diseases. I am most interested in pathogenic mechanisms and pathologic manifestations of glomerular diseases and vasculitis. A major current research focus is on elucidating the pathogenesis of vascular inflammation caused by anti-neutrophil cytoplasmic autoantibodies (ANCA).
Effects of drugs of abuse on maternal behavior and aggression and the effects of prenatal exposure to drugs on offspring development and behavior. Approaches range from molecular to behavioral as our work is basic science with a clinically applicable focus.
Our research focuses on the structure and function of medically important proteins from the crystallographic approach. The current topics include cycolphilin, calcineurin, heat shock protein 90 (hsp90), and cyclic nucleotide phosphodiesterase.
Our research explores the role of hypoxia-inducible factor (HIF) in tumorigenesis. HIF is a transcription factor that plays a key role in oxygen sensing, the adaptation to hypoxia and the tumor microenvironment. It is expressed in the majority of solid tumors and correlates with poor clinical outcome. Therefore, HIF is a likely promoter of solid tumor growth and angiogenesis. Our lab uses mouse models to ask if and how HIF cooperates with other oncogenic events in cancer. We are currently investigating HIF’s role in the upregulation of circulating tumor cells and circulating endothelial cells.
Our focus is on using genetic methods to improve transplantation using ES and hematopoietic stem cells in transplant models. A second focus of the lab uses mutant mice to examine potential drug targets for ameliorating radiation-induced lung damage.
I study a canine model of Duchenne muscular dystrophy. Both conditions occur due to mutations in the dystrophin gene. Our research has defined clinical and pathologic features to better understand disease pathogenesis and to assess treatment.
Research description: Exposure to ambient air particulate matter(PM) has been associated with increased human deaths and cardiopulmonary morbidity, such as lung infections and increased asthma symptoms. I am investigating some types of PM and associated gases (such as aldehydes) that may be associated with those health effects so that the US EPA may be able to better regulate or manage the sources of the PM which are identified as playing a role in the adverse health outcomes. I am currently focusing on the effects of diesel exhaust using a variety of approaches ranging from exposing cultured human cells to the exhaust, to studying responses of humans exposed out in traffic. The EPA rules for diesel exhaust from large trucks to be implemented in 2007 and 2010 will drastically change the type of emissions, and I am currently designing and implementing testing strategies to assess the toxicity of the future types of diesel emissions. Additionally some of my research effort attempts to identify what populations are more sensitive to the effects of air pollutants, and the genetic and environmental reasons behind the increased sensitivity.
Physiology and pharmacology of the basal ganglia; neurobiology of motivation and reward; substance abuse neurobiology; and neurobehavioral teratology.
My laboratory studies the function of neural circuitry involved in the perception of reward and the reinforcement of motivated behaviors in several mouse models of neurodevelopmental disorders, including early developmental exposure to drugs of abuse, such as alcohol or cocaine; and genetic models relevant to the study of autism, such as inactivation of the Fmr1 (Fragile-X Mental Retardation) or MeCP2 (Methyl-CpG Binding Protein) genes. My laboratory employs techniques in behavioral pharmacology, including intracranial self-stimulation (ICSS); in vitro patch-clamp electrophysiology in acute brain slices; and immunohistochemistry with unbiased stereological microscopy.
The overall goal of our laboratory is to obtain new insights into the host-virus interaction, particularly in HIV infection, and translate discoveries in molecular biology and virology to the clinic to aid in the treatment of HIV infection. A subpopulation of HIV-infected lymphocytes is able to avoid viral or immune cytolysis and return to the resting state. Current work focuses on the molecular mechanisms that control the latent reservoir of HIV infection within resting T cells. We have found that cellular transcription factors widely distributed in lymphocytes can remodel chromatin and maintain quiescence of the HIV genome in resting CD4+ lymphocytes. These studies give insight into the basic molecular mechanisms of eukaryotic gene expression, as well as new therapeutic approaches for HIV infection.
Dr. Meshnick studies the molecular epidemiology of malaria and HIV, especially in pregnant women through collaborations in Malawi, the Democratic Republic of the Congo, Thailand and Cambodia. His group is also developing and using novel molecular assays to study the epidemiology and clinical significance of antimalarial drug resistance and to understand the mechanisms of action of antimalarial drugs. His group is also interested in understanding the mechanism of HIV transmission from mother to child and identifying risk factors. Currently, he is using whole genome analyses to further dissect risk factors for transmission.
My laboratory studies diffuse gliomas, devastating primary tumors of the central nervous system for which few effective drugs are currently available. We utilize model systems (genetically engineered mice, cultured cells, and human tumor specimens) to explore the molecular pathogenesis of
and develop drugs and diagnostic markers for individualized therapy of gliomas. Rotating students gain experience with techniques that include genomics (expression microarrays and array CGH), fluorescence microscopy, computer-enhanced image analysis, and tissue microarrays.
Function, expression and trafficking GABA-A receptors in the CNS; effects of chronic ethanol exposure that leads to ethanol tolerance and dependence; role of endogenous neurosteroids on ethanol action and adaptations; etiology of essential tremor.
Mechanisms by which cells control their shape via modulation of the actin cytoskeleton. Palladin, a novel cytoskeletal protein, may be involved in organizing the actin cytoskeleton as a scaffolding protein and may contribute to changes in cell shape.
The Patterson laboratory has 4 major focuses, each of which is funded by at least one major grant. Our longest ongoing project focuses on blood vessel growth and development, and in particular how bone morphogenetic protein signaling regulates vascular development. A second ongoing project in the laboratory is to understand at a fundamental level the cellular response to proteotoxic stress. The third major focus of our laboratory studies cardiac-specific ubiquitin ligases that regulate cardiac hypertrophy and metabolism. Finally, we have begun a human translational study that takes advantage of our expertise in genomics, proteomics, and genetics to develop an integrated DNA/RNA/protein profile database of patients with heart disease.
Human carcinomas show great diversity in their morphologies, clinical histories and in their responsiveness to therapy. This wide tumor diversity poses the main challenge to the effective treatment of cancer patients. The main focus of the Perou Lab is to characterize the biology diversity of human tumors using microarray analysis, genomics, molecular genetics, and cell biology, and then to mimic these findings in animal models. We ultimately use these animal systems to develop predictive computational models and to test new therapeutics that are specific for each tumor subtype.
The main focus of our research is to examine the molecular and cellular mechanisms that are involved in conferring neural identity to stem cells during embryogenesis and the adult.
Dr. Preston's research interests address fundamental genetic and biochemical questions related to autoimmune diseases that affect the kidney. A recent discovery by Dr. Preston and coworkers led to the formulation of a novel theory that delineates potential "triggers" that lead to autoantibody production (Nature Medicine 10: 72-79, 2004). Dr. Preston works closely with the research team within the UNC Kidney Center,including the Director of the Center, Ronald Falk, MD. and the Clinical Core, which obtains biologic samples
from patients for research purposes. These interactions provide the perfect setting for a truly Translational Research Program within the UNC Kidney Center
Bioinformatics, Cancer Biology, Cell Biology, Chemical Biology, Computational Biology, Genomics, Molecular Medicine, Neurobiology, Pharmacology, Systems Biology, Toxicology, Translational Medicine
Projects involve the study of cellular and molecular events involved in autoimmunity, and development and application of genetic vaccines to prevent and treat autoimmunity and cancer.
We are interested in understanding how autoreactive B cells become re-activated to secrete autoantibodies that lead to autoimmune disease. Our research is focused on understanding how signal transduction through the B cell antigen receptor (BCR) and Toll Like Receptors (TLR) lead to secretion of autoantibodies in Systemic Lupus Erythematosus (SLE).
My laboratory is interested in characterizing the role of cytoplasmic signal transduction pathways in regulation of androgen receptor activity and progression of prostate cancer. Our studies have focused on HER-2 receptor tyrosine kinase and we have demonstrated that HER-2 activation stimulates androgen receptor activity and HER-2 inhibition inhibits androgen receptor transcriptional function at the level of recruitment to the androgen responsive enhancers. These findings have led to the design and initiation of the protocol involving lapatinib, a clinical HER-2 inhibitor, in treatment of patients with prostate cancer. More recently, we have demonstrated that activated Cdc42-associated kinase Ack1 promotes progression of prostate cancer via tyrosine phosphorylation of androgen receptor at Tyr-267 and Tyr-363
residues. We are interested in further characterizing the role of tyrosine phosphorylation of androgen receptor in prostate cancer and development of Ack1 targeted therapy for clinical use.
We investigate the role of cardiac specific proteins (Muscle Ring Finger or MuRF proteins) that regulate glucose and fatty acid metabolism, cardiac muscle mass, and sarcomere protein metabolism in the context of common cardiac diseases. Recently, we have identified that MuRF proteins have ubiquitin ligase activity, which enables them to interact with specific proteins, post-translationally modify them with ubiquitin, and subsequently target them for degradation. We focus on mouse models of disease using transgenic and knock-out mice, integrating cardiac physiology with several imaging modalities including echocardiography, Doppler, and SPECT. Since several of the models we have created involve developmental defects, we investigate in utero cardiac function and signaling pathways
with this state of the art of imaging. Our overall goal is to determine how the ubiquitin proteasome system specifically regulates the heart at the molecular level and determine how this affects cardiac function, in order to
translate these findings into therapies & diagnostics for common cardiac diseases such as heart failure and myocardial infarction.
Cellular, molecular, and biochemical mechanisms of blood coagulation; Relationships between cells (monocytes, fibroblasts, endothelial cells, smooth muscle cells, platelets and others), plasma protein concentration, thrombin generation and blood clots; Fibrin formation, structure and stability; Mechanical properties of fibrin; Disorders associated with bleeding and thrombosis, including hemophilia and cardiovascular disease (heart attack, stroke, deep vein thrombosis, pulmonary embolism); Preclinical testing of hemostatic and antithrombotic drugs
