Pharmaceutical and Biomedical Sciences (PBS)

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.

You will find information below on PBS research in Molecular Pharmaceutics, Molecular Pharmacology, Drug Discovery and Medicinal Chemistry and Molecular Toxicology.

Clinical and Administrative Pharmacy (CAP)

The Department of Clinical and Administrative Pharmacy has 3 major components: Clinical Pharmacy, Clinical and Experimental Therapeutics and Pharmaceutical Health Services, Outcomes, and Policy. Together they make up a diverse and thriving department with locations in Athens, Augusta, Albany and Savannah.

We offer doctor of pharmacy, residency and graduate programs in partnership with leading healthcare providers. Our goal is to be nationally and internationally recognized in the areas of public health, drug policy, pharmacoeconomics and outcomes related to drug therapy. We intend to be a leading program for therapeutics-related research that connects the basic science laboratory with clinical practice.

Our Clinical and Experimental Therapeutics ( CET)  group, jointly based at the University of Georgia in Athens and Augusta University in Augusta, conducts nationally and internationally recognized translational research from laboratory to patient bedside.  For more information visit the CET page here. You will find information below on the Atherosclerosis Lab, Cancer and Vascular Biology Lab and Stoke Lab.

Our Pharmaceutical Health Services, Outcomes and Policy (PHSOP) group, located in Athens, conducts both research and practice focused on health economics and pharmacoeconomics, public health policy, and analysis of the outcomes of health care delivery with the aim of improving outcomes in health services and pharmaceutical care delivery.  For more information visit the PHSOP page here.

Molecular Pharmaceutics (PBS)

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.

Molecular Pharmacology (PBS)

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 (PBS)

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.

Molecular Toxicology (PBS)

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.

Atherosclerosis Lab (CAP)

Principal Investigator:  Dr. Lakshman Segar

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 (CAP)

Principal Investigator:  Dr. Somanath Shenoy

Lab Overview

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.

Funding

Current research funding

  1. R01HL103952 (NIH R01 from NHLBI); 06/01/2011-05/31/2018; Protein kinase B (Akt)-mediated pathway regulating endothelial barrier function, Role: PI.
  2. 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
  3. 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.
  4. Wilson Pharmacy Foundation Grant: miR-669h-3p regulation in metastatic prostate cancer(2017-18)
  5. Translational Research Initiative Grant: Identifying biomarkers and therapeutic targets for the deadly lung diseases (2017-2019)

Completed research projects

  1. 0830326N: (PI) Scientist Development Grant (American Heart Association, National) (2008 – 2012).
  2. R01HL071625 06/01/2003-05/31/2007. PI: Dr. Tatiana V. Byzova; Role: Co-Investigator
  3. I01 BX000891 (VA Merit), 04/01/2011-03/31/2015, PI: Dr. Susan C. Fagan; Role: Co-Investigator
  4. 13PRE17100070 (American Heart Pre-doc fellowship-Abdalla) Role: Sponsor 07/01/2013-06/30/15
Stroke Lab (CAP)

Principal Investigator:  Dr. Susan Fagan

Lab Overview

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:

  1. To determine the contribution of acute blood pressure lowering to recovery after ischemic stroke.
  2. To determine the impact of vascular protection on neuronal survival.
  3. 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.

Vision Research Lab (CAP)

Principal Investigator: Dr. Priya Narayanan

Lab Overview

Major focus of our laboratory is to identify therapeutic targets for vision disorders by understanding the mechanisms regulating neurovascular damage in the retina. Retinal neurovascular injury is a major cause of vision impairment in disorders such as diabetic retinopathy, optic neuritis and retinopathy of prematurity, affecting both children and adults worldwide. The major goal of our current studies is to identify the molecular pathways of retinal Spermine Oxidase (SMOX, an important enzyme in polyamine catabolic pathway) regulation and its therapeutic potential under pathological conditions in the retina.

Project 1: Spermine oxidase as a therapeutic target neurodegeneration in diabetic retinopathy. Diabetic retinopathy (DR) is a significant public health issue and the leading cause of vision loss in working aged adults in the US. The available therapies so far are focused on the later stage of diabetes and have adverse side effects. Hence there is a great need for therapies for early stages of DR. Recent studies have shown that retinal neurodegeneration is an early event in DR progression; however, the mechanisms underlying this process are poorly understood.  Our goal is to contribute to the treatment of DR, by defining the specific role of Spermine Oxidase (SMOX) in causing neuronal injury and RGC death in the diabetic retina and demonstrating its potential as a therapeutic target for DR treatment. Studies from our laboratory using diabetic mouse models have shown that expression of SMOX and its downstream byproduct acrolein are increased in diabetic retina. Treatment with SMOX inhibitor, MDL 72527 improved diabetes-induced decrease in retinal structure and function. Studies are in progress to identify the mechanisms involved in SMOX-induced neurodegeneration in diabetic retina. The question we are addressing now is the SMOX regulated molecular mechanisms involved in the retinal damage and dysfunction in diabetic retina. Using the transgenic mouse model overexpressing SMOX in retinal neurons, we are investigating SMOX regulated mechanisms of neurodegeneration in diabetic retina and the therapeutic potential of SMOX inhibition in the prevention and treatment of diabetic retinopathy. These studies have already supported by an NIH R01 from the National Eye Institute.

Project 2: Mechanisms of neurovascular damage in ischemic retinopathy: Role of spermine oxidase. Neuronal and vascular damage to the retina are the major causes of vision loss in diseases such as diabetic retinopathy, retinopathy of prematurity and glaucoma. We have been investigating the impact of polyamine oxidase in mediating retinal neurovascular damage using different retinal injury models. Studies using the Oxygen Induced Retinopathy (OIR) model, we have shown that arginase and its downstream signaling partner, polyamine oxidase are involved in mediating hyperoxia-induced neuronal damage and dysfunction (Narayanan et al 2014). Further studies in our laboratory have shown that treatment with polyamine oxidase inhibitor improved neurovascular damage and glial activation in OIR retina (Patel et al 2016).  We also identified the involvement of activated microglia in mediating neurovascular damage to the retina.  Ongoing studies in our laboratory are investigating the mechanisms by which microglia derived microparticles mediate retinal neurovascular damage and dysfunction in ischemic retinopathy models. Utilizing the models of ischemic retinopathy (OIR and Ischemia/Reperfusion injury) and NMDA induced-retinal excitotoxicity and SMOX transgenic mice, we are addressing the mechanisms by which neurons, glia, and vasculature interact in mediating visual dysfunction.

Project 3: Role of arginase/polyamine signaling in multiple sclerosis mediated retinal neuronal damage and visual dysfunction. Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination, inflammatory responses, and neurodegeneration. Visual dysfunction, resulting from optic neuritis is the first and one of the most common clinical manifestations of MS and can lead to temporary or permanent vision loss. Current medications available for MS are only partially effective as they specifically target the inflammatory phase, but not the neurodegenerative phase, and therefore have limited effects on long-term disability. Thus, there is a great need for identifying new agents that target both inflammatory and neurodegenerative phases of MS and optic neuritis. Considering the major regulatory role of arginase in nitric oxide signaling, and the mitochondrial localization of arginase 2 (A2), we hypothesize that A2 plays a crucial role in the neurodegeneration/visual dysfunction associated with MS. Demonstrating the involvement of arginase and its downstream signaling partner, polyamine oxidase would be of great importance in identifying new therapeutic targets for treating vision problems in MS patients.  Our laboratory has developed the EAE mouse model for studying MS associated neurodegeneration in the retina. We are currently investigating the changes in arginase and SMOX signaling and retinal structural and functional studies. These studies have been supported by pilot awards from National Multiple Sclerosis Society and Augusta University Culver Vision Discovery Institute. Our studies will evaluate the potential therapeutic benefits of targeting arginase/polyamine signaling pathways for treating MS patients in reducing vision problems.

Funding

Current funding

5 R01 EY028569; 05/01/2018 – 04/30/2023; National Eye Institute; Mechanisms of neurodegeneration in diabetic retinopathy: Role of spermine oxidase; Role:  PI

5I01BX001233-01;10/01/2015 – 09/30/2019; VA Merit Review Award; PI: Caldwell; Title: Mechanisms of Traumatic Retinopathy: Role of Arginase; Role: Co-I

Completed funding

PP-1606-08778;11/1/2016-1/31/2018; National Multiple Sclerosis Society; Role of arginase in Multiple Sclerosis Mediated Retinal Neuronal Injury; Role: PI

ESA00036; Extramural Success Award (Augusta University); 10/1/2017- 4/30/2018; Title: Mechanisms of neurodegeneration in diabetic retinopathy: Role of Spermine Oxidase Role: PI

 

5 R01 EY011766-15; 03/01/2013 – 02/28/2018; NIH/National Eye Institute; Title: PI: Caldwell; Cellular Mechanisms of Retinopathy: Role of Arginase; Role: Co-I

11SDG7440088;   07/01/2011 – 06/30/2015; American Heart Association – Scientist Development Grant; Title:  Role of neuronal arginase on vascular protection during ischemic retinopathy; Role: PI

 

Research Directory

To view a directory for research collaboration for Pharmaceutical and Biomedical Sciences and Clinical and Administrative Pharmacy, click here.