The Department of Pharmaceutical and Biomedical Sciences is an interdisciplinary department with research emphasis in the basic science areas of molecular pharmacology, molecular pharmaceutics,drug discovery and medicinal chemistry, and molecular toxicology. Areas of expertise that cross normal discipline limits include but are not limited to drug formulation, design and delivery, and injury prevention resulting from weapons of mass destruction and bioterrorism.
Students will gain experimental as well as theoretical expertise in an area of concentration and are expected to develop the competencies needed for leadership in academia, industry and government agencies. Graduate students perform their dissertation research under the guidance of PBS faculty engaged in diverse research spanning all major disciplines of pharmaceutical sciences. Most faculty members’ research programs are highly interdisciplinary and collaborative with extensive overlap among the areas.
Pharmaceutics is the study of relationships between physiochemical properties of drugs, their formulations and the effects on pharmacokinetics (absorption, distribution, metabolism and elimination of drugs) and pharmacodynamics (therapeutic responses of drugs). It is a highly interdisciplinary science that integrates chemistry, biochemistry, cellular/molecular biology, pathophysiology, engineering, mathematics and therapeutics. PBS faculty is actively engaged in all areas of pharmaceutics using biochemical, cellular and whole-animal models, with a focus on cancer and infectious diseases. Specific strengths are in the understanding of the molecular and cellular determinants of drug transport; the development of polymeric and nonoparticulate drug-carriers; drug delivery approaches that improve drug disposition; and the computational modeling of the properties that govern pharmacological responses.
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.
Drug Discovery and Medicinal Chemistry
Medicinal chemistry examines the chemical design of active pharmacological agents through an understanding of the molecular biology of pharmacological targets using quantitative structure activity relationships and computational methods. Compounds are synthesized by innovative medicinal chemistry methodologies. Our faculty’s research emphasizes the discovery and synthesis of antiviral, anticancer, antiprotozoal and antibacterial agents. Investigators use x-ray crystallography to define the atomic-level architecture of potential drug targets and analytical chemistry to detect drugs and drug products in dosage forms through high-performance liquid chromatography, gas chromatography, capillary electrophoresis and mass spectrometry.
Toxicology, a major branch of pharmacology, is focused on the adverse effects of chemicals on humans and other living organisms. Such chemicals can include established pharmaceutics, experimental/developmental drugs and nonoparticles. Other chemicals of interest include environmental pollutants, such as volatile hydrocarbons and environmental oxidants. Our faculty is actively engaged in research projects with a focus on the ability of these agents to include multiple pathologies including cancer, neurodegenerative disease, infectious disease, cardiovascular disease, and muscular dystrophies.
Our ongoing research is aimed at understanding the molecular mechanisms of atherosclerosis and fatty liver disease. Atherosclerosis is characterized in part by accumulation of lipids (e.g., cholesterol) in the arterial wall and phenotypic changes in vascular smooth muscle cells (VSMCs). Fatty liver disease, also referred to as hepatic steatosis, is characterized by accumulation of lipids in the form of droplets (e.g., triglycerides) in hepatocytes. The primary focus of our lab is to investigate altered growth factor signaling in VSMCs and dysregulated fatty acid metabolism in hepatic tissues in metabolically compromised conditions such as obesity, diabetes, and dyslipidemia.
Cancer and Vascular Biology Lab
Our long-term goal in the cancer and cardiovascular biology laboratory is to enable the development of new and innovative therapeutics for the prostate and bladder cancers, lung edema and pulmonary fibrosis through better understanding of the molecular mechanisms regulating tumor growth and metastasis, vascular permeability, angiogenesis and extracellular matrix remodeling.
In the area of cancer, we focus on determining the molecular mechanisms regulating tumor growth, invasion and metastasis of urological cancers with an emphasis on developing therapeutics employing studies using pre-clinical mouse models. In the area of pulmonary fibrosis, we are investigating the molecular mechanisms mediating the myofibroblast trans-differentiation mediated by a transforming growth factor-β (TGFβ)-fibroblast growth factor (FGF) interplay and identify novel targets for therapeutic interventions. In the area of acute lung injury, our research is centered on identifying how different pathological stimuli induce vascular injury and inflammation in the exudative phase of acute respiratory distress syndrome (ARDS) that progresses to endothelial to mesenchymal transition (EndMT), fibroprolifetaion, vascular remodeling and inflammation. Our interest is also in understanding the mechanisms that mediate the switch from injury resolution to fibrosis.
Current research funding
- R01HL103952 (NIH R01 from NHLBI); 06/01/2011-05/31/2018; Protein kinase B (Akt)-mediated pathway regulating endothelial barrier function, Role: PI.
- PC150431 (DOD-PCRP) Idea Development Award 04/01/2016-03/31/2019; Secretory Phospholipase A2-Responsive Liposomal Delivery of IPA-3 for Prostate Cancer Therapy
- UL1-TR000454 (KL2-TR000455 and TL1-TR000456 by NCATS) 10/01/2017-09/30/2022
Title: Georgia Clinical and Translational Science Alliance (GaCTSA) by the Atlanta Clinical and Translational Science Institute (ACTSI) (PI- Robert Taylor, Emory University)
Role: Co-Director (UGA) for the KL2-TR000455 and the TL1-TR000456 Training Component.
- Wilson Pharmacy Foundation Grant: miR-669h-3p regulation in metastatic prostate cancer(2017-18)
- Translational Research Initiative Grant: Identifying biomarkers and therapeutic targets for the deadly lung diseases (2017-2019)
Completed research projects
- 0830326N: (PI) Scientist Development Grant (American Heart Association, National) (2008 – 2012).
- R01HL071625 06/01/2003-05/31/2007. PI: Dr. Tatiana V. Byzova; Role: Co-Investigator
- I01 BX000891 (VA Merit), 04/01/2011-03/31/2015, PI: Dr. Susan C. Fagan; Role: Co-Investigator
- 13PRE17100070 (American Heart Pre-doc fellowship-Abdalla) Role: Sponsor 07/01/2013-06/30/15
Diabetes and Vascular Function Lab
The overall goal of the Diabetes and Vascular Function laboratory is to better understand the regulation of vascular function and structure in diabetes in order to prevent, delay or reverse diabetes-associated complications including stroke and cognitive impairment. In collaboration with Dr. Susan Fagan, we have made the interesting observation that there is significant cerebral neovascularization in type 2 diabetic rats and when ischemia/reperfusion injury occurs, diabetic animals develop bleeding into the brain, a dreaded complication of stroke. Our efforts are focused on how diabetes alters the expression and function of key mediators that are critical for vascular integrity and function. These studies are important to identify potential mechanisms contributing to cognitive decline in diabetes as well as identifying how an ischemic injury superimposed on this existing pathology affect functional outcomes and recovery following stroke. In addition, based on the clinical evidence which suggests that acute hyperglycemic patients suffer the worst outcomes of stroke, in collaboration with Dr. Askiel Bruno from Department of Neurology, we are investigating the mechanisms that mediate greater vascular and neuronal injury in hyperglycemic stroke.
Effect of Diabetes and Acute Hyperglycemia on Ischemic Brain Injury. This project focuses on the effects of diabetes-induced changes in the microvascular structure and function on increased risk of stroke as well as mechanisms of worsened stroke outcome in diabetes. Microvascular Remodeling and Vascular Complications in Obesity and Diabetes: This project seeks to determine the physiological and molecular mechanisms of increased cerebral angiogenesis and arteriogenesis in diabetes and obesity.
Maha Coucha, BPharm, Graduate student
Aisha Kelly, MS, Graduate student
Weiguo Li, MD, PhD, Postdoctoral associate
Mohammed Abdelsaid, Postdoctoral associate
Handong Ma, Research associate
Dr. Susan C. Fagan is a Professor of Pharmacy at the University of Georgia and has dedicated her career to the identification of new treatment strategies for acute ischemic stroke patients. As a clinical pharmacy scientist, she was a key member of the federally-funded investigative team that developed the clot busting drug, tPA, as a treatment for stroke in the early 1990s. The manuscript was published in the New England Journal of Medicine in December, 1995, impacting the way in which stroke patients are treated worldwide. This research led to the adoption of tPA as the ONLY US Food and Drug Administration-approved pharmacologic treatment for stroke, in 1996.
Since 1994, Dr. Fagan has been searching for new molecular targets, activated after a patient experiences a stroke, which can be modified by novel treatments to improve patient outcome. Frustrated by the lack of clinical efficacy of the neuroprotective compounds studied extensively in the 1990s, she initiated a 15 year journey to develop vascular protection as a way to first, improve the safety of tPA (reducing brain bleeding) and secondly, to improve recovery after ischemia and reperfusion in the brain. Her landmark manuscript, published in Stroke, in 2004, identified likely targets and was followed by a series of federally-funded investigations (2 NIH RO1s and 2 VA Merit Review) to develop pharmacologic interventions that approach those targets. Many of the compounds are currently under investigation in human stroke patients (minocycline, atorvastatin, and candesartan) by Dr. Fagans’ research team at the Augusta University or by other investigators.
Dr. Fagan has published more than 140 peer reviewed journal articles and 15 book chapters. She is recognized as an international expert in ischemic stroke treatment and is a consultant for the National Institutes of Health (NIH), Washington University, Massachusetts General Hospital (Harvard), and the University of Texas Health Sciences Center San Antonio on issues regarding the development of new treatments for stroke and other neurologic disorders.
Dr. Fagan has been recognized for her unique contributions to “translational research” as evidenced by her appointment as a faculty member on two national clinical research training programs. The first, funded by the National Institutes of Neurologic Disorders and Stroke (NINDS), was for neurologists and neurosurgeons (2008- 2010) and the second, for clinical pharmacy scientists (2009 – 2011) was funded by the American College of Clinical Pharmacy (ACCP) Research Institute. She was elected Chair of the ACCP Research Institute in 2008. She is the current chair of the Research and Development Committee of the Charlie Norwood VA Medical Center in Augusta, GA.
Her status in the field has also been recognized by her appointment to several different NIH study sections and by her invitation to exclusive research conferences, funded by NIH (Princeton Conferences are limited to 100 participants). These honors are only bestowed on those with nationally and internationally recognized leadership in research.
The Next Five Years
The past two years have witnessed an explosion of productivity in the Fagan Stroke Laboratory. Following up on a novel finding of a proangiogenic state in the cerebrospinal fluid of animals treated with a vascular protective medication acutely after stroke (Kozak, 2009), the group reported a differential expression of growth factors in BOTH hemispheres of the brain after unilateral ischemia (Guan, 2011). This challenges the decades-long notion that the contralateral hemisphere is a good “control” for measuring changes in molecular mediators after stroke. The next five years will be focused on determining the mechanisms of accomplishing vascular protection after acute ischemic stroke and the impact of vascular protection on functional outcome. The specific goals are:
- To determine the contribution of acute blood pressure lowering to recovery after ischemic stroke.
- To determine the impact of vascular protection on neuronal survival.
- To determine the contribution of premorbid vascular health to recovery after ischemia and reperfusion
These will be accomplished using both in vitro and in vivo models of cerebral ischemia and reperfusion in combination with both pharmacologic, immunologic and genetic manipulation and state of the art molecular and imaging techniques.