Research Interest: Drug Discovery
| Name | PhD Program | Research Interest | Publications |
|---|---|---|
| Fenton, Owen PUBLICATIONS |
PHD PROGRAM RESEARCH INTEREST |
The broad aim of research in the Fenton Laboratory is to develop and evaluate synthetic drug delivery platforms to treat neurodegenerative disorders in the brain using RNA therapeutics. RNA therapeutics represent a particularly promising class of therapeutics for neurodegenerative management given their ability to tune levels of specific protein expression in living systems. For example, protein downregulation can be achieved by administering short interfering RNAs (siRNAs); alternatively, proteins can be upregulated by messenger RNA (mRNA) administration. Despite this promise, fewer than 0.05% of the world’s clinically approved drugs are RNA therapeutics, and their translation to neurodegenerative disorders in the brain warrants further study at the fundamental and clinical levels. To address these challenges, our group focuses on the discovery and development of molecular carriers and technology platforms to improve the targeting, safety, and efficacy of RNA drugs within target cells. Specifically, our group leverages an interdisciplinary approach to develop lipid nanoparticles (LNP) as well as soft matter hydrogel platforms that can serve as carrier systems and/or drug delivery models for RNA drugs. Further, our group also explores the development of technological platforms to further expand the potential of RNA drugs within resource limited settings. Lastly, given that mRNA drugs can be engineered to encode for virtually any polypeptide or protein based antigen, our group also aims to leverage our platformable LNP technologies for the study and prevention of cancers and infectious disease. In undertaking such an approach, the goal of our research is to equip students with fundamental skillsets for the development of next generation drugs while simultaneously developing clinically-relevant carrier platforms and technologies for the study, prevention, and treatment of human disease. |
| Willson, Tim WEBSITE PUBLICATIONS |
PHD PROGRAM RESEARCH INTEREST |
A unifying goal of my research is the use of chemistry as a tool to illuminate human biology. For over two decades I have led programs to develop potent cell active chemical probes to identify and study the biological function of their target proteins. Starting in 1992 with the orphan nuclear receptors, my lab developed chemical probes to uncover the roles of PPAR, PPAR, LXR, FXR, CAR, and PXR in human physiology. The release of our chemical probes into the public domain supported research across the global scientific community and resulted in multiple drug candidates to treat diseases of human metabolism entering clinical development. I am co-discoverer of the FXR agonist obeticholic acid, which was approved by the FDA in 2016 as a drug for the treatment of Primary Biliary Cholangitis. In 2007, I started a collaboration with the Structural Genomics Consortium (SGC) to discover chemical probes for the enzymes and reader domains involved in epigenetic regulation. Together, we built a consortium with support from public funders and eight pharmaceutical companies that has released over 40 high quality chemical probes into the public domain. We demonstrated that the bromodomain family of acetyl lysine reader domains were highly tractable targets for drug discovery, which led to the development of BRD4 inhibitors for the treatment of various rare cancers. In 2015, I established the first US site of the SGC at the University of North Carolina in Chapel Hill to expand the footprint of open science in US academia. I have assembled a team at SGC-UNC to create chemical tools for understudied (‘dark’) kinases, identify inhibitors of molecular targets that cause rare diseases, and develop chemical probes for proteins associated with neurodegenerative diseases. With support from the NIH Illuminating the Druggable Genome program we assembled a Kinase Chemogenomic Set (KCGS): the largest, highly annotated and publicly available collection of small molecule kinase inhibitors. We used KCGS to identify kinases whose inhibition prevents replication of coronaviruses including SARS-CoV-2. Medicinal chemists at the SGC-UNC are also developing chemical probes within the Med Chem Core of the NIA Target Enablement to Accelerate Therapy Development for Alzheimer’s Disease (TREAT-AD) program at UNC. |
| Li, Zibo WEBSITE PUBLICATIONS |
PHD PROGRAM RESEARCH INTEREST |
My research has focused on developing new radio-chemistry, imaging probes, and therapeutic approaches including nanomedicine for various diseases. Most importantly, we have the culture of forming an active collaboration with people in different field. With a cGMP lab located within our facility, we are also experienced on developing lead agents and translate it to clinic. |
| Coleman, Leon WEBSITE PUBLICATIONS |
PHD PROGRAM RESEARCH INTEREST |
The overriding goal of Dr. Coleman’s work is to identify novel treatments for alcohol use disorders (AUD) and associated peripheral disease pathologies. Currently, this includes: the role of neuroimmune Signaling in AUD pathology, the role of alcohol-associated immune dysfunction in associated disease states, and novel molecular and subcellular mediators of immune dysfunction such as extracellular vesicles, and regenerative medicine approaches such as microglial repopulation. |
| Axtman, Alison WEBSITE PUBLICATIONS |
PHD PROGRAM RESEARCH INTEREST |
In my lab, we are exploring the roles that kinases play in neurodegeneration through the creation of high-quality, small molecule tools. Our team designs, synthesizes, and evaluates small molecules capable of kinase modulation, sometimes targeting kinase inhibition and sometimes kinase activation. In order to accomplish our aims, we work closely with X-ray crystallographers within the larger SGC and with biologists, including experts in using stem cells to model neurodegenerative diseases. We seek enthusiastic students with an interest in neuroscience who are willing to learn and apply techniques that span chemistry and biology to better understand and address neurodegeneration. |
| Jiang, Guochun WEBSITE PUBLICATIONS |
PHD PROGRAM RESEARCH INTEREST |
Antiretroviral therapy (ART) is effective in suppressing HIV-1 replication in the periphery, however, it fails to eradicate HIV-1 reservoirs in patients. The main barrier for HIV cure is the latent HIV-1, hiding inside the immune cells where no or very low level of viral particles are made. This prevents our immune system to recognize the latent reservoirs to clear the infection. The main goal of my laboratory is to discover the molecular mechanisms how HIV-1 achieves its latent state and to translate our understanding of HIV latency into therapeutic intervention. Several research programs are undertaking in my lab with a focus of epigenetic regulation of HIV latency, including molecular mechanisms of HIV replication and latency establishment, host-virus interaction, innate immune response to viral infection, and the role of microbiome in the gut health. Extensive in vitro HIV latency models, ex vivo patient latency models, and in vivo patient and rhesus macaque models of AIDS are carried out in my lab. Multiple tools are applied in our studies, including RNA-seq, proteomics, metabolomics, highly sensitive digital droplet PCR and tissue RNA/DNAscope, digital ELISA, and modern and traditional molecular biological and biochemical techniques. We are also very interested in how non-CD4 expression cells in the Central Nervous System (CNS) get infected by HIV-1, how the unique interaction among HIV-1, immune cells, vascular cells, and neuron cells contributes to the initial seeding of latent reservoirs in the CNS, and whether we can target the unique viral infection and latency signaling pathways to attack HIV reservoirs in CNS for a cure/remission of HIV-1 and HIV-associated neurocognitive disorders (HAND). We have developed multiple tools to attack HIV latency, including latency reversal agents for “Shock and Kill” strategy, such as histone deacetylase inhibitors and ingenol family compounds of protein kinase C agonists, and latency enforcing agents for deep silencing of latent HIV-1. Several clinical and pre-clinical studies are being tested to evaluate their potential to eradicate latent HIV reservoirs in vivo. We are actively recruiting postdocs, visiting scholars, and technicians. Rotation graduate students and undergraduate students are welcome to join my lab, located in the UNC HIV Cure Center, for these exciting HIV cure research projects. |
| Cameron, Craig E. WEBSITE PUBLICATIONS |
PHD PROGRAM RESEARCH INTEREST |
Our laboratory now studies mechanisms of genome replication and pathogenesis of respiratory enteroviruses and evolution of neurovirulence using the tools of mechanistic enzymology, cell biology, stem-cell engineering, and virology. Our laboratory is also pioneering the development of tools to monitor viral infection dynamics on the single-cell level, aka “single-cell virology.” |
| Button, Brian WEBSITE PUBLICATIONS |
PHD PROGRAM RESEARCH INTEREST |
The Button lab in the Department of Biochemistry and Biophysics is part of the Marsico Lung Institute. Our lab is actively involved in projects that are designed to define the pathogenesis of muco-obstructive pulmonary disorders and to identify therapies that could be used to improve the quality of life in persons afflicted by these diseases. In particular, our research works to understand the biochemical and biophysical properties of mucin biopolymers, which give airway mucus its characteristic gel-like properties, and how they are altered in diseases such as Asthma, COPD, and cystic fibrosis. |
| Drewry, David H WEBSITE PUBLICATIONS |
PHD PROGRAM RESEARCH INTEREST |
The Drewry lab is focused on designing, synthesizing, evaluating, and sharing small molecule chemical probes for protein kinases. These tools are used to build a deeper understanding of disease pathways and facilitate identification of important targets for drug discovery. Through wide ranging partnerships with academic and industrial groups, the Drewry lab is building a Kinase Chemogenomic Set (KCGS) that is available to the community for screening. |
| Mei, Hua WEBSITE PUBLICATIONS |
PHD PROGRAM RESEARCH INTEREST |
We focus on the translational potential and clinical impact of biomedical research. Our general research interest is to reveal the mechanisms of eye diseases using animal and other research models. One current project is to investigate the markers of limbal stem cells using transgenic mice. The lack of limbal stem cell marker has been a long-term bottleneck in the diagnosis and treatment of limbal stem cell deficiency, which leads to a loss of corneal epithelial integrity and damaged limbal barrier functions with the symptoms of persistent corneal epithelial defects, pain, and blurred vision. The research results will directly impact on the early-stage diagnosis of the disease and the quality control of ex vivo expanded limbal stem cells for transplantation. |