Faculty Database:
[Research Interest: Drug Discovery]

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NameEmailPhd ProgramResearch InterestsPublications
Aubé, Jeffrey email , , , publications

Our lab develops new chemistry, and chemical agents as biological probes and drug discovery candidates. Current interests include the discovery of unconventional opioid agents, anti-tuberculosis drugs, and basic biochemistry of androgen biosynthesis inhibitors.

 

Bowers, Albert A email , , , , publications

Research in the Bowers lab focuses on investigation of structure activity relationships and mechanisms of action of natural product-derived small molecule therapeutics.  We employ a variety of methods to build and modify compounds of interest, including manipulation of natural product biosynthesis, chemical synthesis, and semi-synthesis.  One major area of research in the lab is the rationale engineering of biosynthetic pathways to make bacterial drug factories.  Compounds targeting transcriptional regulation of cancer as well as multi-drug resistant venereal infections are currently under investigation in the lab.

Burks, Wesley email , , , , publications

The UNC Food Allergy Institute (UNCFAI) was established in 2012 to address the growing needs of children and adults with food allergy. Program investigators study the biologic basis of food allergy in the laboratory and in clinical research studies seeking to better understand the role of allergen-specific IgE and the mechanism of allergen immunotherapy. The Institute provides comprehensive, family-centered patient care for food allergy, food-related anaphylaxis, and other related disorders like atopic dermatitis and eosinophilic esophagitis.

Carney, Paul R. email , , , publications

A central theme of my work is that I combine engineering and neuroscience with medical research to develop more effective therapies for neurological disease. This leverages my experience as both a clinician scientist and engineer. The passion that drives my career is the search for better ways to prevent and treat epilepsy which affects over 60 million people worldwide.

I lead a long-term effort to define structural and functional biomarkers of epileptic networks and seizure generation to enable more precise diagnostics and effective antiepileptic therapies. Because effective treatment and cure in epilepsy typically require an understanding of neural systems and fundamental processes, my research strives to combine studies of basic questions with applied research. Our goal is to advance the translation of biomedical discoveries into applications that improve clinical outcomes. Although my research spans the continuum from basic to applied questions, it focuses mostly on systems neuroscience and provides a strong scientific basis for implementing antiepileptic strategies. I engage and innovate in the areas of signal processing, computational neuroscience, brain imaging, cell signaling, and gene therapy. Clinical translation is an important goal of my work, in addition to mentoring clinicians and scientists across fields. Involvement of graduate students and postdoctoral fellows is a critical aspect of my research program. Through the research process, I strive to train students in basic concepts, research methodology, management strategies, and philosophies of science. I also take enjoyment from expanding my research program horizons in new areas of the world and with new research questions and technologies.

Cohen, Todd email , , , , publications

My research aims to uncover the molecular aspects of protein aggregation diseases (also called PAD) which include neurodegenerative diseases (such as Alzheimer’s disease and Amyotrophic Lateral Sclerosis), myofibrillar myopathies (such as muscular dystrophies), as well as the formation of age-related cataracts.  Although very distinct, these disorders share a common underlying pathogenic mechanism.  Using a combination of biochemistry and in vitro approaches, cell biology, and primary cells / transgenic mouse models, we will investigate the post-translational modifications (PTMs) that drive these disease processes. Ultimately, this research will provide a platform for future drug discovery efforts against these devastating diseases.

Conlon, Brian P. email , , , , publications

My lab is focused on the improvement of treatment of chronic bacterial infections. We aim to determine the mechanisms of antibiotic tolerance. Our aim is to understand the physiology of the bacterial cell, primarily Staphylococcus aureus, during infection and how this physiology allows the cell to survive lethal doses of antibiotic. We will use advanced methods such as single cell analysis and Tn-seq to determine the factors that facilitate survival in the antibiotic’s presence. Once we understand this tolerance, we will develop advanced screens to identify novel compounds that can be developed into therapeutics that can kill these drug tolerant “persister” cells and eradicate deep-seated infections.

Darville, Lee Antoinette (Toni) email , , , , publications

Research in the Darville lab is focused on increasing our understanding of immune signaling pathways active in development of genital tract disease due to Chlamydia trachomatis and determination of chlamydial antigen-specific T cell responses that lead to protection from infection and disease. In vitro, murine model, and human studies are being performed with the ultimate goal to develop a vaccine against this prevalent sexually transmitted bacterial pathogen. Genetic and transcriptional microarray studies are being performed to explore pathogenic mechanisms and determine biomarkers of pelvic inflammatory disease due to Chlamydia as well as other sexually transmitted pathogens.

Hathaway, Nathaniel A. email , , , , , publications

The Hathaway lab is focused on understanding the biological events responsible for dynamically regulating the selective expression of the mammalian genome. In multicellular organisms, genes must be regulated with high precision during stem cell differentiation to achieve normal development. Pathologically, the loss of proper gene regulation caused by defects in chromatin regulatory enzymes has been found to be a driving force in cancer initiation and progression. My lab uses a combination of chemical biology and cell biology approaches to unravel the molecular mechanisms that govern gene expression. We utilize new tools wielding an unprecedented level of temporal control to visualize changes in chromatin structure and function in mammalian cells and animal models. In addition, we seek to identify small molecule inhibitors that are selective for chromatin regulatory enzymes with the potential for future human therapeutics.

James, Lindsey Ingerman email , , publications

We are interested in modulating the activity of chromatin reader proteins with small-molecule ligands, specifically potent and selective chemical probes, in order to open new avenues of research in the field of epigenetics. Our work has pioneered the biochemical assays and medicinal chemistry strategies for high quality probe development for methyl-lysine (Kme) reader proteins, as well as the means by which to evaluate probe selectivity, mechanism of action, and cellular activity. Using a variety of approaches, we utilize such chemical tools to improve our understanding of their molecular targets and the broader biological consequences of modulating these targets in cells. We are also interested in developing novel methods and screening platforms to discover hit compounds to accelerate Kme reader probe discovery, such as affinity-based combinatorial strategies, as well as innovative techniques utilizing our developed antagonists to more fully understand the dynamic nature of chromatin regulation.

Jin, Jian email , publications

Research in the Jian Jin lab focuses on the following two main areas: (1) discovering chemical probes for histone methyltransferases (HMTs), a class of more than 50 epigenetic writers that play a critical role in diverse biological processes including chromatin compaction, gene expression, transcriptional regulation, and cell differentiation; and (2) creating functionally selective ligands of G protein-coupled receptors (GPCRs) for treating various central nervous system (CNS) disorders.

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.

 

Matsushima, Glenn K email , , , , , , publications

Our laboratory is interested in innate immune responses during injury to the central nervous system and during inflammation during microbial infections.  Our laboratory has a special interest in autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus.  We also are pursuing drug discovery projects targeting receptors that may modulate demyelinating disease and immune responses.  We use molecular, cellular and biochemical approaches both in vitro and in vivo to identify the function of key mediators during pathogenesis.

Pearce, Ken email , , , , , publications

We are a comprehensive, collaborative group with a primary focus on lead and early drug discovery for oncology and epigenetic targets and pathways.  Our research applies reagent production, primary assay development, high-throughput screening, biophysics, and exploratory cell biology to enable small molecule drug discovery programs in solid partnership with collaborators, both within the Center for Integrative Chemical Biology and Drug Discovery and across the UNC campus.  We apply small molecule hit discovery to highly validated biochemical targets as well as phenotypic cell-based assays.  Our methods include various fluorescence-based readouts and high content microscopy.  Examples of some of our collaborative small molecule discovery programs include, inhibition of chromatin methyl-lysine reader proteins, hit discovery for small GTPases such as K-Ras and Gaq, inhibitors of inositol phosphate kinases, inhibitors of protein-protein interactions involving CIB1 and MAGE proteins, and several cell-based efforts including a screen for compounds that enhance c-Myc degradation in pancreatic cancer cells.  In addition, we are developing a DNA-encoded library approach for hit discovery to complement traditional high-throughput screening.  Our ultimate goal is discovery of new chemical probes and medicines for exploratory biology and unmet medical needs, respectively.

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.

Rubenstein, David email , , , , publications

The work in my lab is focused on the regulation of cell adhesion and the inter-relationship between alterations in adhesion and the biology of the cell. Our lab has made several key observations on the molecular mechanisms by which acantholysis proceeds in the human autoimmune blistering diseases pemphigus vulgaris and pemphigus foliaceus.  The presence or absence of adhesion represents a major biologic shift requiring coordination amongst various biological processes, including those regulating adhesion, migration, proliferation, differentiation, and cell death.  The intracellular regulatory and signalling events observed in pemphigus acantholysis likely represent variations of normal physiologic mechanisms regulating the presence/absence of desmosome-mediated cell-cell adhesion in epidermal epithelia.  We proposes that these events are important for regulating transitions in cell-adhesion and likely have a central role in adhesion transitions occuring during such processes as wound healing, tumor cell proliferation and invasion.  Current projects in the lab are focused on furthering work on the mechanism of pemphigus acantholysis as well as elucidating the role of desmosomes in wound healing and cancer biology.

Taylor, Anne Marion email , , publications

Local mRNA translation is critical for axon regeneration, synapse formation, and synaptic plasticity. While much of research has focused on local translation in dendrites and in peripheral axons, less is known about local translation in smaller diameter central axons due to the technical difficulty of accessing them. We developed microfluidic technology to allow access to axons, as well as nascent boutons and fully functional boutons. We identified multiple transcripts that are targeted to cortical and hippocampal axons in rat (Taylor et al. J Neurosci 2009). Importantly, this work countered the prevailing view that local mRNA translation does not occur in mature axons. We are actively investigating transcripts in axons that may play a role in establishing proper synaptic connections. We are also using our technology to identify transcripts targeted to axons and boutons in human neurons. These studies are a critical step towards the identification of key genes and signaling molecules during synapse development, axonal regeneration, and proper circuit function.

Williams, David C. Jr. email , , , , publications

The overall objective of our research is to understand the connection between structure of protein-DNA complexes, protein dynamics and function.  We currently focus on the methyl-cytosine binding domain (MBD) family of DNA binding proteins.  The MBD proteins selectively recognize methylated CpG dinucleotides and regulate gene expression critical for both normal development and carcinogenesis.  We use a combination of NMR spectroscopy and biophysical analyses to study protein-DNA and protein-protein complexes involving the MBD proteins.  Building on these studies, we are developing inhibitors of complex formation as potential molecular therapeutics for b-hemoglobinopathies and cancer.

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.