Faculty Database:
[ Phd Program: Biochemistry & Biophysics ]

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NameEmailPhd ProgramResearch InterestsPublications
Asokan, Aravind email , , , , , publications

Our research group is focused on combining the tools and principles of molecular biology and genetics with chemistry to generate a synthetic viral toolkit. The lab-derived synthetic viral entities are utilized to dissect mechanisms of viral tissue tropism, as new reagents for applications in genomics and proteomics and as new vectors for human gene therapy applications.

Bergmeier, Wolfgang email , , , , , publications

Our research focuses on the adhesion mechanisms of platelets and neutrophils to sites of vascular injury/ activation. For successful adhesion, both cell types rely on activation-dependent receptors (integrins) expressed on the cell surface. We are particularly interested in the role of calcium (Ca2+) as a signaling molecule that regulates the inside-out activation of integrin receptors. Our studies combine molecular and biochemical approaches with microfluidics and state-of-the-art in vivo imaging (intravital microscopy) techniques.

Bloom, Kerry email , , , , , , publications

Our objective is to understand the dynamic and structural properties of chromosomes during mitosis.  We use live cell imaging techniques to address how kinetochores are assembled, capture microtubules and promote faithful segregation of chromosomes.

Campbell, Sharon email , , , , publications

Current research projects in the Campbell laboratory include structural, biophysical and biochemical studies of wild type and variant Ras and Rho family GTPase proteins, as well as the identification, characterization and structural elucidation of factors that act on these GTPases.  Ras and Rho proteins are members of a large superfamily of related guanine nucleotide binding proteins.  They are key regulators of signal transduction pathways that control cell growth. Rho GTPases regulate signaling pathways that also modulate cell morphology and actin cytoskeletal organization.  Mutated Ras proteins are found in 30% of human cancers and promote uncontrolled cell growth, invasion, and metastasis. Another focus of the lab is in biochemical and biophysical characterization of the cell adhesion proteins, focal adhesion kinase, vinculin, paxillin and palladin.  These proteins are involved in actin cytoskeletal rearrangements and cell motility, amongst other functions. Most of our studies are conducted in collaboration with laboratories that focus on molecular and cellular biological aspects of these problems. This allows us to direct cell-based signaling, motility and transformation analyses. Member of the Molecular & Cellular Biophysics Training Program.

Carter, Charles email , , , , , , publications

Molecular evolution and mechanistic enzymology find powerful synergy in our study of aminoacyl-tRNA synthetases, which translate the genetic code. Class I Tryptophanyl-tRNA Synthetase stores free energy as conformational strain imposed by long-range, interactions on the minimal catalytic domain (MCD) when it binds ATP.  We study how this allostery works using X-ray crystallography, bioinformatics, molecular dynamics, enzyme kinetics, and thermodynamics. As coding sequences for class I and II MCDs have significant complementarity, we also pursuing their sense/antisense ancestry.  Member of the Molecular & Cellular Biophysics Training Program.

Chen, Xian email , , , , publications

Developing and applying novel mass spectrometry (MS)-based proteomics methodologies for high throughput identification, quantification, and characterization of the pathologically relevant changes in protein expression, post-translational modifications (PTMs), and protein-protein interactions.  Focuses in the lab include: 1) technology development for comprehensive and quantitative proteomic analysis, 2) investigation of systems regulation in toll-like receptor-mediated pathogenesis and 3) proteomic-based mechanistic investigation of stress-induced cellular responses/effects in cancer pathogenesis.

Cheney, Richard email , , , , , , publications

Our goal is to understand the fundamental cell biology underlying processes such as neurodevelopment, angiogenesis, and the metastasis of cancer cells.  Most of our experiments focus on molecular motors such as myosin-X and on the finger-like structures known as filopodia.  We generally utilize advanced imaging techniques such as TIRF and single-molecule imaging in conjunction with mammalian cell culture.  We also  use molecular biology and biochemistry and are in the process of developing a mouse model to investigate the functions of myosin-X and filopodia.   We are looking for experimentally driven students who have strong interests in understanding the molecular basis of dynamic cellular processes such as filopodial extension, mechanosensing, and cell migration.

Clemmons, David R email , , , , , , publications

Cross-talk between insulin like growth factor -1 and cell adhesion receptors in the regulation of cardiovascular diseases and complications associated with diabetes.

Cook, Jeanette (Jean) email , , , , , , , publications

The Cook lab studies the major transitions in the cell division cycle and how perturbations in cell cycle control affect genome stability. We have particular interest in mechanisms that control protein abundance and localization at transitions into and out of S phase (DNA replication phase) and into an out of quiescence. We use a variety of molecular biology, cell biology, biochemical, and genetic techniques to manipulate and evaluate human cells as they proliferate or exit the cell cycle. We collaborate with colleagues interested in the interface of cell cycle control with developmental biology, signal transduction, DNA damage responses, and oncogenesis.

Crews, Stephen email , , , , , , publications

Research in the lab is focused on a genetic, cellular, and molecular understanding of Drosophila developmental neuroscience, including the following research areas – (1) Neuronal formation and differentiation, (2) Glial formation, migration, and axon-glial interactions, (3) Synaptic connectivity, and (4) Transcriptional regulation.

Dohlman, Henrik email , , , , , , publications

We use an integrated approach (genomics, proteomics, computational biology) to study the molecular mechanisms of hormone and drug desensitization. Our current focus is on RGS proteins (regulators of G protein signaling) and post-translational modifications including ubiquitination and phosphorylation.

Dokholyan, Nikolay email , , , , , publications

The mission of my laboratory is to develop and apply integrated computational and experimental strategies to understand, sense, and control misfolded proteins, and uncover the etiologies of human diseases. UNDERSTAND: We are working toward understanding of the protein misfolding diseases, such as Lou Gehrig’s disease and cystic fibrosis.. Other areas of interest include HIV, Graft versus Host disease (fatal autoimmune response to bone marrow transplant), and understanding and developing new drugs for pain. SENSE: We are working toward developing genetically-encoded proteins that bind and report rare/intermediate conformations of target molecules (proteins and RNA). CONTROL: We are working toward developing genetically-encoded proteins that control target proteins with light and/or drugs. We have developed novel approach for drug activation/deactivation of kinases, and light-activatable protein to manipulate protein function with light. We are working toward extending these approaches to other classes of proteins and on multiplexing, whereby we selectively activate/control several distinct cellular pathways via targeting several proteins simultaneously.

Dowen, Jill email , , , , , , publications

My lab studies how genes function within the three-dimensional context of the nucleus to control development and prevent disease. We combine genomic approaches (ChIP-Seq, ChIA-PET) and genome editing tools (CRISPR) to study the epigenetic mechanisms by which transcriptional regulatory elements control gene expression in embryonic stem cells.  Our current research efforts are divided into 3 areas: 1) Mapping the folding pattern of the genome 2) Dynamics of three-dimensional genome organization as cells differentiate and 3) Functional analysis of altered chromosome structure in cancer and other diseases.

Errede, Beverly email , , , publications

Yeast molecular genetics; MAP-Kinease activation pathways; regulation of cell differentiation.

Griffith, Jack email , , , , , , publications

We are interested in basic DNA-protein interactions as related to – DNA replication, DNA repair and telomere function.  We utilize a combination of state of the art molecular and biochemical methods together with high resolution electron microscopes.

Kaufman, David G. email , , , , , publications

Topic 1  We seek genomic targets for carcinogenesis among segments of DNA replicated in early S phase when cells are most susceptible to carcinogens.  We are mapping genomic sites replicated during early S phase, identifying origins of replication activated in this interval, and characterizing temporal sequencing of replication from these origins.  Topic 2  We are reconstructing differentiated and functional human endometrial tissue from epithelial and stromal cells interacting in culture.  We use these co-cultures to study development of endometrial cancer.

Ke, Hengming email , , , , publications

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.

Kuhlman, Brian email , , , , publications

We use a combination of experimental and computational methods to redesign protein-protein interactions.  The potential applications for this technology include enhancing protein therapeutic and creating new tools to study signaling pathways.

Lai, Samuel email , , , , , , , , publications

Our dynamic group are broadly involve in three topics: (i) prevention of infectious diseases by harnessing interactions between secreted antibodies and mucus, (ii) immune response to biomaterials, and (iii) targeted delivery of nanomedicine.  Our group was the first to discover that secreted antibodies can interact with mucins to trap pathogens in mucus.  We are now harnessing this approach to engineer improved passive and active immuniation (i.e. vaccines) at mucosal surfaces, as well as understand their interplay with the mucosal microbiome.  We are also studying the adaptive immune response to polymers, including anti-PEG antibodies, and how it might impact the efficacy of PEGylated therapeutics.  Lastly, we are engineering fusion proteins that can guide targeted delivery of nanomedicine to heterogenous tumors and enable personalized medicine.

Lee, Andrew email , , , , publications

We study protein structure and dynamics as they relate to protein function and energetics. We are currently using NMR spectroscopy (e.g. spin relaxation), computation, and a variety of other biophysical techniques to gain a deeper understanding of proteins at atomic level resolution.  Of specific interest is the general phenomenon of long-range communication within protein structures, such as observed in allostery and conformational change.  A. Lee is a member of the Molecular & Cellular Biophysics Training Program.

Lentz, Barry email , , , , publications

The regulatory role of platelet membrane phosphatidylserine in blood coagulation; mechanism of protein-mediated membrane fusion in secretory processes and virus infection.  Director of the Molecular & Cellular Biophysics Training Program.

Liu, Pengda email , , , , publications

If you are interested in developing new biochemical/molecular techniques/tools to advance our understanding of biology, and if you are interested in signal transduction pathway analyses and identification of cancer biomarkers, our research group may help you to achieve your goals, as we have the same dreams. We are especially interested in deciphering the molecular mechanisms underlying aberrant signaling events that contribute to tumorigenesis, mediated through protein modifications and protein-protein interactions. Understanding these events may lead to identification of novel drug targets and provide new treatment strategies to combat human cancer.

 

Maddox, Amy Shaub email , , , , , , , publications

My research philosophy is summed up by a quote from Nobelist Albert Szent-Gyorgyi: “Discovery is to see what everybody has seen and to think what nobody has thought.” My lab studies the molecular and physical mechanisms of cell shape change during cytokinesis and tissue biogenesis during development. Specifically, we are defining how cells ensure proper alignment and sliding of cytoskeletal filaments, and determining the shape of the cell throughout division. To do so, we combine developmental biology, cell biology, biochemistry, and quantitative image analysis.

Maddox, Paul S. email , , , publications

My research program is centered on understanding fundamental aspects of cell division. During cell division, complex DNA-protein interactions transform diffuse interphase chromatin into discrete mitotic chromosomes, condensing them several thousand fold to facilitate spatial segregation of sister chromatids. Concomitantly, kinetochores form specifically at centromere regions of chromosomes and regulate force-producing interactions with microtubules. While these processes are absolutely required for genomic stability, the in vivo mechanisms of chromosome and kinetochore assembly remain unsolved problems in biology. I investigate 1) the spatiotemporal regulation of mitotic chromosome assembly, and 2) the molecular basis of centromere specification. To do so, I will combine biochemical approaches with high-resolution light microscopy of live cells, whole organisms, and in vitro systems.

Major, Michael Ben email , , , , , , , , , publications

The overall goal of my lab is to understand how alterations in signal transduction pathways contribute to human cancer.  To that end, a systems level approach is employed wherein functional genomics, mass spectrometry-based proteomics, gene expression and mutation data are integrated.  The resulting cancer-annotated physical/functional map of a signal transduction pathway provides us with a powerful tool for mechanistic discovery in cancer biology.  We are currently working in lymphoma and lung cancer models, with a focus on the Wnt/b-catenin and Keap1/Nrf2 pathways.

Maness, Patricia F. email , , , publications

My research focuses on molecular mechanisms of mammalian nervous system development. We investigate mechanisms by which developing neurons migrate to the neocortex and form connections.

Marzluff, William email , , , , , , , , , publications

We are interested in the mechanisms by which histone protein synthesis is coupled to DNA replication, both in mammalian cell cycle and during early embryogenesis in Drosophila, Xenopus and sea urchins.

McGinty, Robert email , , , , , publications

The McGinty lab uses structural biology, protein chemistry, biochemistry, and proteomics to study epigenetic signaling through chromatin in health and disease.  Chromatin displays an extraordinary diversity of chemical modifications that choreograph gene expression, DNA replication, and DNA repair – misregeulation of which leads to human diseases, especially cancer. We prepare designer chromatin containing specific combinations of histone post-translational modifications. When paired with X-ray crystallography and cryo-electron microscopy, this allows us to interrogate mechanisms underlying epigenetic signaling at atomic resolution.

Meissner, Gerhard email , , , , publications

The goal of the laboratory’s research is to define the structure and function of an intracellular Ca2+ release channel in skeletal and cardiac muscle, using molecular biological and electrophysiological methods and by creating mutant mice.

Neher, Saskia email , , , , , publications

Our lab seeks to better understand the maturation and regulation of a group of human lipases.  We aim to uncover how these lipases properly fold and exit the ER, and how their activity is subsequently regulated.  We study the membrane-bound and secreted proteins that play a role in lipase regulation.  Our research can potentially impact human health as biochemical deficiencies in lipase activity can cause hypertriglyceridemia and associated disorders, such as diabetes and atherosclerosis.  We are an interdisciplinary lab and aim to address these questions using a variety of techniques, including membrane protein biochemistry, enzymology, and structural and molecular biology.

Parise, Leslie email , , , , , , , , publications

The overall goal of our laboratory is to understand the molecular interface between cell signaling and adhesion receptors in blood diseases and cancer in order to develop novel therapeutic targets and approaches. One area of study is platelets because they become activated by cellular signals and adhere to each other and the blood vessel wall via specific adhesion receptors. These events can block blood flow, causing heart attacks and stroke, the leading causes of death in the US. Another area of research is sickle cell disease, since red blood cells in these patients are abnormally adhesive and also cause blood vessel blockages. A third area is cancer since cancer cells use similar cellular signals and adhesion receptors in tumorigenesis and metastasis. Our work involves a wide array  of technologies that include molecular, structural and cellular approaches as well as clinical/translational studies with human patients.

Pielak, Gary J. email , , , , , publications

My graduate students and I use the formalism of equilibrium thermodynamics and the tools of molecular biology and biophysics to understand how nature designs proteins.

Ramsden, Dale email , , , , , publications

The end joining pathway is a major means for repairing chromosome breaks in vertebrates.  My lab is using cellular and cell-free models to learn how end joining works, and what happens when it doesn’t.

Redinbo, Matt email , , , , , , , publications

The Redinbo Laboratory examines dynamic cellular processes using structural, chemical, molecular and cell biology. Our goals are to discover new drugs and to elucidate molecular pathways essential to human disease.  Current projects include developing the first drugs that target the human microbiome, unraveling the nature of innate immunity in the human lung, and discovering how microbial systems exchange genes, including those that encode antibiotic resistance.

Riordan, John email , , publications

The primary research focus is the structure, function and biosynthetic processing of membrane proteins which provide permeability pathways through the membranes of cells. Much of the current work is concentrated on the ion channel protein, CFTR (cystic fibrosis transmembrane conductance regulator) which is absent or dysfunctional in patients with cystic fibrosis. To elucidate the molecular mechanisms of CFTR function, we study single channel properties by electrophysiological techniques, enzymatic activity and physical interaction with other cellular molecules. A major objective of studies with the purified molecule is to obtain 3-dimensional structure information so that small molecules capable of recognizing features of its surface shape can be synthesized and used to modulate its folding and activity.

Sancar, Aziz email , , , , , publications

We have three main areas of research focus: (1) Nucleotide excision repair: The only known mechanism for the removal of bulky DNA adducts in humans. (2) DNA damage checkpoints:  Biochemical pathways that transiently block cell cycle progression while DNA contains damage.  (3) Circadian rhythm:  The oscillations in biochemical, physiological and behavioral processes that occur with the periodicity of about 24 hours.

Sondek, John email , , , , , , publications

Our laboratory studies signal transduction systems controlled by heterotrimeric G proteins as well as Ras-related GTPases using a variety of biophysical, biochemical and cellular techniques. Member of the Molecular & Cellular Biophysics Training Program.

Strahl, Brian D. email , , , , , publications

Our laboratory is examining the role of histone post-translational modifications in chromatin structure and function.  Using a combination of molecular biology, genetics and biochemistry, we are determining how a number of modifications to the histone tails (e.g. acetylation, phosphorylation, methylation and ubiquitylation) contribute to the control of gene transcription, DNA repair and replication.

Swanstrom, Ronald email , , , , , , publications

First, we study the complex HIV-1 population that exists within a person.  We use this complexity to ask questions about viral evolution, transmission, compartmentalization, and pathogenesis.  Second, we are exploring the impact of drug resistance on viral fitness and identifying new drug targets in the viral protein processing pathway.  Third, we participate in a collaborative effort to develop an HIV-1 vaccine.  Fourth, we are using mutagenesis to determine the role of RNA secondary structure in viral replication.

Wang, Greg Gang email , , , , , publications

With an emphasis on chromatin biology and cancer epigenetics, our group focuses on mechanistic understandings of how chemical modifications of chromatin define distinct patterns of human genome, control gene expression, and regulate cell proliferation versus differentiation during development, and how their deregulations lead to oncogenesis. Multiple on-going projects employ modern biological technologies to: 1) biochemically isolate and characterize novel factors that bind to histone methylation on chromatin, 2) examine the role of epigenetic factors (chromatin-modifying enzymes and chromatin-associated factors) during development and tumorigenesis using mouse knockout models, 3) analyze epigenomic and transcriptome alternation in cancer versus normal cells utilizing next-generation sequencing technologies, 4) identify novel oncogenic or tumor suppressor genes associated with leukemia and lymphoma using shRNA library-based screening. We are also working together with UNC Center of Drug Discovery to develop small-molecule inhibitors for chromatin-associated factors as novel targeted cancer therapies.

Wilson, Elizabeth M email , , , , , publications

Our research focus is on mechanisms of action of the androgen receptor (AR), a ligand-dependent transcriptional regulatory protein that mediates the effects of testosterone and dihydrotestosterone. Studies seek to identify and characterize AR coregulatory proteins and their regulation by phosphorylation and the cell cycle. Areas of interest include male sex development, the androgen insensitivity syndrome, and AR action in the ovary, endometrium and prostate cancer. Melanoma antigen gene protein-11 (MAGE-11) was identified as an AR coregulatory protein that belongs to the MAGE gene family of cancer-germline antigens. The MAGE-11 gene is located on the human X chromosome and is exclusively expressed in human and nonhuman primates, providing a gain-of- function to AR. Mechanisms whereby MAGE-11 regulates AR transcriptional activity through its interaction with the AR NH2-terminal FXXLF motif and cell cycle regulatory proteins are being investigated. Our objective is to understand how AR regulates gene transcription and cell proliferation in the human male and female reproductive tracts.  Keywords:  androgen receptor, MAGE-11, male reproduction, female reproduction, prostate cancer, transcription regulation, FXXLF motifs

Wolfenden, Richard email , , publications

Enzymes allow organisms to channel the flow of matter to their own advantage, allowing some reactions to proceed rapidly compared with other reactions that offer no selective advantage to the organism. After a substrate is bound at an enzyme’s active site, its half-life is usually a small fraction of 1 s. Rapid turnover is necessary if any enzyme is to produce a significant rate of reaction at the limited concentration (<10(-5) M) at which enzymes are present within the cell. Many enzymes are known to have evolved to work nearly as efficiently as is physically possible, with second order rate constants that approach their rates of encounter (10(9) M(-1)s(-1) with the substrate in solution. How rapidly would biological reactions occur if an enzyme were not present? Until recently, some reactions were known to require several years, and everyday experience suggests that some reactions are slower still. The survival of paper documents and ancient ships for long periods under water implies that the glycosidic bonds of cellulose, for example, are very resistant to hydrolysis in the absence of cellulases that catalyze their hydrolysis. Why would one wish to know the rate of a biological reaction in the absence of an enzyme? That information would allow biologists to appreciate what natural selection has accomplished in the evolution of enzymes as proficient catalysts and would enable chemists to compare enzymes with artificial catalysts produced in the laboratory. Such information would also be of value in considering the design of enzyme antagonists: the greater the rate enhancement that an enzyme produces, the greater is its affinity for the altered substrate in the transition state compared with its relatively modest affinity for the substrate in the ground state. That principle has furnished a basis for the design of transition state analogues, extremely powerful inhibitors that resemble the transition state and take advantage of that special affinity. Examples have now been discovered for enzymes of every class, including inhibitors that are already used to control hypertension, the spread of HIV, the maturation of insects and the growth of weeds. By allowing snapshots of enzymes in action, transition state analogues have also provided valuable tools for investigating enzyme structures and mechanisms, most recently that of the peptide bond forming center of the ribosome. Those enzymes that produce the largest rate enhancements and transition state affinities should offer the most sensitive targets for inhibitor design. Particularly remarkable are those enzymes that act as simple protein catalysts, without the assistance of metals or other cofactors. To determine the extent to which one such enzyme, human uroporphyrinogen decarboxylase, enhances the rate of substrate decarboxylation; we examined the rate of spontaneous decarboxylation of pyrrolyl-3-acetate. Extrapolation of first-order rate constants measured at elevated temperatures indicates that this reaction proceeds with a half-life of 2.3 x 10(9) years, approaching the age of the Earth. This enzyme shows no significant structural or sequence homology with yeast orotidine 5′-monophosphate decarboxylase, another cofactorless enzyme that catalyzes a very slow reaction. To uncover the mechanisms of action of these remarkable molecules, we are studying these and other enzymes by kinetic and structural methods, site-directed mutation and the study of model reactions. In addition to more traditional methods, these projects make extensive use of new methods that include high-field NMR, isothermal calorimetry, and kinetic experiments in water and other solvents in sealed tubes at very high temperatures.

Xiong, Yue email , , , , , publications

Using genetic, cell biology, biochemical and proteomic approaches to determine the function and mechanism of – (1) CDK inhibitors in development and tumor suppression, (2) the p53 degradation and transport, and (3) RING family of ubiquitin ligases.

Zhang, Qi email , , , , publications

Our laboratory is focusing on developing and applying solution-state NMR methods, together with computational and biochemical approaches, to understand the molecular basis of nucleic acid functions that range from enzymatic catalysis to gene regulation. In particular, we aim to visualize, with atomic resolution, the entire dynamic processes of ribozyme catalysis, riboswitch-based gene regulation, and co-transciptional folding of mRNA. The principles deduced from these studies will provide atomic basis for rational manipulation of RNA catalysis and folding, and for de novo design of small molecules that target specific RNA signals. Research program in the laboratory provides diverse training opportunities in areas of spectroscopy, biophysics, structural biology, computational modeling, and biochemistry.

Zylka, Mark J. email , , , , , , , publications

Our research is focused on two general areas:  1. Autism and 2. Pain.  Our autism research is focused on topoisomerases and other transcriptional regulators that were recently linked to autism.  We use genome-wide approaches to better understand how these transcriptional regulators affect gene expression in developing and adult neurons (such as RNA-seq, ChIP-seq, Crispr/Cas9 for knocking out genes).  We also assess how synaptic function is affected, using calcium imaging and electrophysiology.   In addition, we are performing a large RNA-seq screen to identify chemicals and drugs that increase risk for autism.   /  / Our pain research is focused on lipid kinases that regulate pain signaling and sensitization.  This includes work with cultured dorsal root ganglia (DRG) neurons, molecular biology and behavioral models of chronic pain.  We also are working on drug discovery projects, with an eye towards developing new therapeutics for chronic pain.