The genetic pathways for the development of cardiac and vascular smooth muscle cells. In particular, the transcriptional control of mammalian cardiovascular system, and cell proliferation and differentiation-related human cardiovascular disorders.
The Wang group designs novel data models and algorithms to address fundamental computational issues in analyzing large sets of experimental data. Ongoing research projects include: 1) Classification and clustering analysis of gene-expression profiles, 2) Discovery of discriminative structural motifs in proteins and 3) Query and integration of heterogeneous databases.
To understand the general rules of splicing regulation, a.k.a. "splicing code", we study the splicing regulation in a systematic way. We also try to engineer molecules that can modulate splicing, and use them as drugs to treat splicing diseases.
A goal of the laboratory is to understand viral molecular pathogenesis in the oral cavity. We seek to understand the critical molecular interactions that occur between DNA viruses and the host that govern the development of oral disease.
Our vision is to address one of the great remaining and intractable problems in cellular and molecular biology -- that of determining comprehensive and quantitative structures for all cellular and viral RNAs. To this end, we are developing high-throughput RNA structure analysis technologies (called SHAPE) with the goal of making RNA secondary and tertiary structure analysis as straightforward, in principle, as DNA sequencing is today. We then use these tools to understand otherwise daunting problems that play pivotal roles in cellular function. Current projects include (i) RNA folding and protein assembly reactions central to the infectivity and pathogenesis of human viruses and (ii) assembly of large biomedically important ribonucleoprotein complexes inside living cells.
I’m a neurobiologist who uses immunocytochemistry and electron microscopy to address functional questions. I am trying to elucidate the molecular organization of postsynaptic signaling in the rat cortex and hippocampus. I'm also interested in the actin cytoskeleton of dendritic spines, and how spines may remodel during LTP.
The laboratory is interested in the role of G proteins and G protein-coupled receptors in the regulation of mammalian cell metabolism, growth control and differentiation. Specific questions addressed by the lab include (1) What are the structural determinants of G-protein-coupled receptors that regulate their interactions with G proteins and with proteins such as kinases and arrestins that are involved in receptor desensitization? and (2) What roles exist for G protein-coupled pathways in the growth and differentiation of mammalian cells? Rhodopsin, the photoreceptor of the mammalian retinal rod, is used as a molecular model for defining the domains of G protein-coupled receptors responsible for the binding and activation of their specific G proteins. Experiments also focus on the mechanism of desensitization of this receptor by phosphorylation and arrestin binding.
How the loss of different components of the SWI/SNF complex contributes to neoplastic transformation remains an open and important question. My laboratory concentrates on addressing this question by the combined use of biological, biochemical and mouse models for SWI/SNF complex function.
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.
Construction of chimeric antithrombotic proteins targeted to endothelial cell surfaces; Activity of these using in vitro assays and in vivo mouse models of arterial and venous thrombosis; pathophysiology of hemostasis/thrombosis in these mouse models.
Our research is in viral pathogenesis and vaccine development for viral diseases that affect resource-poor countries. Specific areas of interest include a) innate immune responses to viral infection, b) vaccines for dengue fever, and c) maternal antibody interference with vaccination.
My research interests are wide ranging, including topics in conservation biology and plant ecology. I have had several foci: species richness (including the All Taxa Biodiversity Inventory in Great Smoky Mountains National Park, beta diversity (including the comparison of diversity in different parts of the world that have similar climates and the connections to coinservation planning),and the ecology of natural disturbances (including connections to environmental ethics and conservation of biodiversity). Through my role as Director of the University's North Carolina Botanical Garden, a conservation focused garden, I am also involved in research and poliy in invasive species biology, ecological restoration, ex situ conservation and reintroduction of rare species, and related subjects.
The Wilhelmsen lab is engaged in the genetic mapping of susceptibility loci for complex neurological diseases and has been developing large-scale automated gene mapping technologies to facilitate these mapping efforts. They have invested heavily in automation that enables high-throughput genotyping and data processing. As data accumulates, this will enable parametric and nonparametric linkage analysis of large numbers of traits at regular intervals for the entire genome. The Wilhelmsen lab is applying these techniques to two projects: (1) the genetics of alcoholism and (2) positional cloning of the gene responsible for a family of disorders called frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17).
My lab concentrates on studying the molecular genetic basis of the evolutionary processes of adaptation and speciation. The questions we ask are what are the sequence changes that lead to variation between species and diversity within species, and what can these changes tell us about the processes that lead to their evolution. We use a number of different techniques to answer these questions, including molecular biology, sequence analyses (i.e. population genetics and molecular evolution techniques), physiological studies, and examinations of whole-organism fitness. Currently work in the lab has focused on a intertidal copepod species that is an excellent model for the initial stages of speciation (and also provides opportunities to study how populations of this species adapt to their physical environment).
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.
Our work focuses on molecular aspects of androgen receptor regulation of gene expression, which includes coactivator interactions with the androgen receptor and its functional importance in various clinical syndromes.
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
Enzyme action; drug design; effects of solvent water on the structure and reactivity of biological molecules; rates of benchmark reactions for testing the catalytic prowess of enzymes.
Our research focuses on the mechanisms used by the bacterium Pseudomonas aeruginosa to cause disease. We are interested in identifying signal transduction pathways that regulate the expression of virulence genes in response to the host environment.
