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NameEmailPhD ProgramResearch InterestPublications
Frankowski, Kevin
WEBSITE
EMAIL
PUBLICATIONS

PHD PROGRAM
Pharmaceutical Sciences

RESEARCH INTEREST
Chemical Biology, Drug Discovery, Translational Medicine

We are inspired by the diversity and complexity found in natural products and use their architecture as both a platform for developing chemical methods and as scaffolds for new molecular tools in chemical biology. We have employed our chemical synthesis skill set to solve emerging challenges facing modern medicine. This has led to ongoing collaborative projects in metastatic cancer, hepatitis C antivirals, dopamine signaling and sigma receptor ligands. Of particular interest is the development of next generation anti-metastasis agents to our recent phase I clinical candidate, metarrestin.

Mulikova, Tomiris

EMAIL

PHD PROGRAM

RESEARCH INTEREST
Chemical Biology, Pharmacology, Structural Biology

Liu, Tongkun (Louis)

EMAIL

PHD PROGRAM

RESEARCH INTEREST
Chemical Biology, Drug Discovery, Pharmacology

Frasineanu, Anca

EMAIL

PHD PROGRAM

RESEARCH INTEREST
Cell Biology, Chemical Biology, Neurobiology

Augoustides, Victoria

EMAIL

PHD PROGRAM

RESEARCH INTEREST
Chemical Biology, Computational Biology, Drug Delivery

Willson, Tim
WEBSITE
EMAIL
PUBLICATIONS

PHD PROGRAM
Pharmaceutical Sciences

RESEARCH INTEREST
Chemical Biology, Drug Discovery

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.

Axtman, Alison
WEBSITE
EMAIL
PUBLICATIONS

PHD PROGRAM
Pharmaceutical Sciences

RESEARCH INTEREST
Cell Biology, Cell Signaling, Chemical Biology, Drug Discovery

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
EMAIL
PUBLICATIONS

PHD PROGRAM
Biochemistry & Biophysics

RESEARCH INTEREST
Behavior, Biochemistry, Cell Biology, Cell Signaling, Chemical Biology, Drug Discovery, Immunology, Metabolism, Molecular Biology, Molecular Medicine, Neurobiology, Pathogenesis & Infection, Pharmacology, Translational Medicine, Virology

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.

Drewry, David H
WEBSITE
EMAIL
PUBLICATIONS

PHD PROGRAM
Pharmaceutical Sciences

RESEARCH INTEREST
Cancer Biology, Chemical Biology, Drug Discovery, Pharmacology, Structural Biology

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.

Liu, Rihe
WEBSITE
EMAIL
PUBLICATIONS

PHD PROGRAM
Pharmaceutical Sciences

RESEARCH INTEREST
Biochemistry, Biophysics, Cell Signaling, Chemical Biology, Nanomedicine

The research interests of the Liu Lab are in functional proteomics and biopharmaceuticals. Currently we are working on the following projects:  (1). Using systems biology approaches to decipher the signaling pathways mediated by disease-related proteases such as caspases and granzymes and by post-translationally modified histones. We address these problems by performing functional protein selections using mRNA-displayed proteome libraries from human, mouse, Drosophila, and C. elegans. (2). Developing novel protein therapeutics and nucleic acid therapeutics that can be used in tumor diagnosis, treatment, and nanomedicine. We use various amplification-based molecular evolution approaches such as mRNA-display and in vivo SELEX to develop novel single domain antibody mimics on the basis of very stable protein domains or to generate aptamers on the basis of nuclease-resistant nucleic acids, that bind to important biomarkers on the surface of cancer cells. We further conjugate these biomarker-binding affinity reagents to small molecule drugs or nanoparticles for targeted delivery of therapeutic agents. (3). Identifying the protein targets of drugs or drug candidates whose action mechanisms are unknown. We combine molecular proteomic and chemical biology approaches to identify the protein targets of drugs whose target-binding affinities are modest.