Pharmacology, the study of the effects of drugs on biologic systems and their therapeutic applications, is a multi-disciplinary field including biochemistry, structural biology, physiology, cell biology and pathology. Our faculty members study the pharmacology of drugs at the molecular, cellular and whole animal levels, as well as the underlying mechanisms of action. The pharmacology of traditional small-molecule drugs and natural product-derived nutraceuticals are also actively investigated.
Faculty members & their research interests
Dr. Beedle’s laboratory studies the biology and disease of the dystrophin-glycoprotein complex. This complex is an important structural link between the intracellular cytoskeleton and the extracellular matrix. Dystroglycan, a primary component of the complex, undergoes extensive glycosylation of its protein core. If these glycans are disrupted, dystroglycan can no longer bind to the extracellular matrix and muscular dystrophy develops affecting a range of tissues including skeletal and cardiac muscle, brain, and eye. In her lab, Dr. Beedle’s group uses genetically modified mice, cell culture and molecular biology to study dystroglycan disease mechanisms, processing enzymes, and therapeutic strategies. Techniques such as conditional gene knockout strategies, animal physiology, biochemistry, genetics, molecular biology, cell culture and histology are used.
Dr. Cummings’ laboratory studies molecular mechanisms involved in cell death, with a particular emphasis on the role of lipids. His team is interested in cell death induced by anti-cancer agents and environmental oxidants. Previous work demonstrated roles of phospholipase A2 (PLA2) in apoptosis and necrosis in numerous cell types. The laboratory uses lipidomic approaches, such as two-dimensional, high performance, thin-layer chromatography in tandem with electrospray ionization mass spectrometry (2D-HP-TLC-ESI-MS), to identify lipids altered in prostate cancer cells and kidney cells exposed to anti-cancer agents. Recent work has also used lipidomics to determine how lipid-based nanoparticles are degraded by PLA2 in cancer cells. They hope to use these data to design and track novel nanoparticulate drug carriers and understand their mechanisms of action.
The Cummings laboratory also studies the molecular mechanisms of cell death induced by water disinfection byproducts (DBPs) such as bromate, which are environmental oxidants. Recent studies show that this class of compounds causes kidney cell death by DNA-dependent and independent mechanisms, and that mixtures of these compounds can induce either apoptosis or necrosis. Current studies are focused on epigenetic changes induced in kidney cells after chronic exposure to low levels of DBPs.
Dr. Franklin’s research is on the mechanisms underlying neuronal apoptosis with a focus on the basic cellular mechanism by which mitochondria contribute to this type of neuronal death, as well as the role of mitochondria in Alzheimer’s disease. He is also studying drug discovery for treatment of filaria infections in humans, animals and plants in collaboration with Dr. Adrian Wolstenholme at the UGA Veterinary College.
Dr. Greenspan’ s research interests center on the health benefits of nutraceuticals and functional foods; these terms can be broadly defined as natural food products that are ingested or incorporated into the diet to help slow the progression of certain disease states. In the past several years, Dr. Greenspan has investigated the effect of muscadine grape extracts (Georgia is a major producer of this Southern specialty grape) and select sorghum bran extracts on important biological processes such as inflammation, protein glycation and LDL oxidation. These pathways are thought to be the underlying cause of two of the most prevalent diseases in America, coronary heart disease and diabetes. It is interesting to note that while natural products have been shown to inhibit protein glycation and LDL oxidation both in vitro and in vivo, there is currently no FDA approved drug designed to arrest these critical disease pathways. Dr. Greenspan’s work in natural product research has led to the commercialization of numerous products both in the United States and on international markets.
The Hooks laboratory studies the molecular mechanisms by which cellular signaling regulates cell function, and how these signaling mechanisms go awry in cancer and central nervous system disorders. Specifically, we study G-protein signaling cascades and their dynamic regulation by activating receptors and deactivating RGS proteins (Regulator of G-protein Signaling proteins). We have a long-standing interest in a family of receptors activated by Lysophosphatidic Acid (LPA) and Sphingosine 1-phosphate (S1P), which are important bioactive lipid growth factors that play important roles in normal physiology and in the development of cancer and inflammatory/immune diseases. We are also exploring the ability of RGS proteins to attenuate these effects and impact disease progression. Research from the our lab has demonstrated that RGS proteins inhibit oncogenic LPA signaling in ovarian cancer cells, blunting LPA-stimulated kinase signaling cascades and growth, migration and survival responses. Our recent studies have focused on the RGS protein RGS10, and we have recently demonstrated that RGS10 is epigenetically silenced in cancer cells, which contributes to the development of chemoresistance. In addition to its role in cancer, RGS10 has been shown to play a critical role in neuroinflammation, a major feature of multiple neural diseases including Parkinson’s disease, Multiple Sclerosis, and neuropathic pain. Our current focus is on defining the function and regulation of RGS proteins in cancer and neuroinflammatory disease using a combination of cellular, molecular, and genetic approaches.
Dr. Murph’s laboratory focuses on therapeutic questions of two diseases, melanoma and serous epithelial ovarian carcinoma. For both malignancies, treating patients is coupled with major clinical frustrations, like chemoresistance; this is where science can aid in developing therapeutics and molecular strategies to overcome such obstacles. Enormous progress has been made in the fight against breast and prostate cancer, and childhood leukemia that it is time all cancer subtypes mimic that success. Recently, drugs such as Ipilimumab and Vemurabenib, which treat melanoma, bolster the hope that additional options will soon become available.
Another example of medical therapeutic challenges occurs among women with ovarian cancer. These patients receive debulking surgery followed by adjuvant chemotherapy that reduces their tumors to an undetectable level. Essentially, treatment initially works very well and most patients enjoy a time of remission. However, this is deceiving since 75 to 85 percent of these women will return to the clinic within 18 to 24 months with refractory tumors. The Murph laboratory investigates this question in an attempt to find molecular mechanisms of exploration to either prevent chemoresistance from developing, or prolonging the period of remission by extending the time until chemo resistance develops in slow progressing dormant cells. Chemoresistance will also be a major challenge in melanoma patients. Thus, the development of chemoresistance in mammalian cells is a continuous problem requiring resolution that will ultimately benefit many cancer types.
Chronic pain and hyperalgesia affect hundreds of thousands of Americans who get little or no relief from the limited treatments currently available. Current research in Dr. Weng’s laboratory focuses on the synaptic and molecular mechanisms related the pathogenesis of pain. They are determining neuroplasticity in the spinal dorsal horn in animal pain models induced by nerve injury or inflammation.
Specifically, the Weng laboratory is studying the roles of glial glutamate transporters and proinflammatory cytokines in the plasticity of sensory synapses in the spinal dorsal horn. Multiple cutting edge research techniques are used in Dr. Weng’s laboratory, including cellular physiology, pharmacology, systems behavior and molecular biology techniques. His work has been published in high-impact journals and supported by the NIH grants.
Prostate cancer is the second leading cause of cancer-related deaths in men in North America. Several funding agents have invested in the study of this disease. The pathological stages of prostate cancer begin with abnormal epithelial proliferation and prostatic intraepithelial neoplasia, with progression to invasive carcinoma, and eventually metastatic disease, the stage in which most patients die.
In our research, we use a mouse model to recapitulate the progression of invasive stages of prostate cancer in vivo to understand the genesis of the disease, and to find drugs to target cancer cells in this stage. Our study takes advantage of adult stem cells existing in mouse prostate tissue. Provided with a suitable microenvironment, the stem cells will regenerate into prostate tissue. This regeneration system allows us to evaluate the ability of epithelial stem and progenitor cells to form normal prostate tissue, but also to assess the tumorigenic potential of oncogenes. In assistance with the capability of the isolation of adult stem cells and lentiviral transduction, my lab has successfully used the system to evaluate one single oncogene or the synergy of multiple oncogenes in prostate epithelium and the paracrine factors in the mesenchymal compartment in promoting prostate tumorigenesis.
Our on-going studies focus on the crosstalk of oncogenic signaling pathways, which will help us understand the initiation of invasive prostate cancer in vivo and identify drugs to target prostate tumorigenesis using genetic approaches and in complement small molecule inhibitors. The long term goal of my lab is to interrogate the molecular mechanisms underlying advanced prostate carcinoma and provide the scientific rationale for using small molecule inhibitors to suppress aggressive prostate cancer.