Principal Investigators

Project 1: Inhibitors of Coronavirus Fidelity and Cap Methylation as Broadly Applicable Therapeutics

PI: Mark R. Denison, Vanderbilt University
CoI: Ralph Baric, University of North Carolina – Chapel Hill

Project 2: Novel Therapeutic Strategies Targeting Re-emerging Alphaviruses

PI: Daniel N. Streblow, Oregon Health & Science University
Co-I: Mark Heise, University of North Carolina – Chapel Hill

Project 3: Identification and Development of Anti-Flavivirus Lead Drug Candidates

PI: Jay A. Nelson, Oregon Health & Science University
PI: Pei-Yong Shi, PhD
Co-I: Michael S. Diamond, Washington University

Project 4: Identification and characterization of novel drugs that target the Influenza virus polymerase functions

PI: Richard J. Whitley, University of Alabama at Birmingham
Co-I: Babu L. Tekwani, Southern Research

Richard J. Whitley

Dr. Whitley is a Distinguished Professor of Pediatrics, Professor of Microbiology, Medicine and Neurosurgery; Loeb Eminent Scholar Chair in Pediatrics; Co-Director, Division of Pediatric Infectious Diseases; Vice-Chair, Department of Pediatrics; Senior Scientist, Department of Gene Therapy; Scientist, Cancer Research and Training Center; Faculty, Gene Therapy Center; Associate Director for Drug Discovery and Development and Senior Leader, Pediatric Oncology Program, Comprehensive Cancer Center; Director, UAB Center for Emerging Drug Discovery; Co-Founder and Co-Director, Alabama Drug Discovery Alliance. Dr. Whitley is responsible for the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group whose continuing role is to perform clinical trials of antiviral therapies directed against medically important viral diseases of children and adults including viruses considered as threats to human health. Dr. Whitley's other research interest is in the translation of molecular biology to clinical application, particularly in the development of human monoclonal antibodies for therapy of herpesvirus infections and engineering of herpes simplex virus for gene therapy. In these latter studies, he and his colleagues have engineered herpes simplex virus to serve as a vector for foreign gene expression. He received his B.A. in chemistry from Duke University and his M.D. from the George Washington University. He subsequently completed an internship in pediatrics and a fellowship in infectious diseases/virology at the University of Alabama at Birmingham. He has published over 337 articles. He participates in numerous Data Safety and Monitoring Boards for ongoing clinical studies. In June of 2009, he was tapped to serve as a member of the Novel H1N1 Influenza Working Group of the President’s Council of Advisors on Science and Technology (PCAST). He is a past President of the Infectious Diseases Society of America (IDSA) and received the UAB President's Medal in 2007. In 2013, he was named as the inaugural recipient of the Distinguished Clinical Research Scholar and Educator in Residence at the NIH Clinical Center.

J. Robert Bostwick

Dr. Bostwick has a diverse academic and pharmaceutical industry background with extensive experience in project portfolio management, assay development, and implementation of automated laboratory processes. With thirty years of combined experience in academia and the pharmaceutical industry his breadth of experience also includes conducting and managing research projects, directing scientific operations, and building scientific programs and teams to successfully execute them. He has routinely managed portfolios of multiple screening projects with combined annual operating budgets of over $4 million and has been involved in more than 50 different drug discovery programs engaged in in vitro biochemical and cell-based screening while serving in various roles including group, section, department and project leadership. His experience working within global organizations has equipped him with leadership and administrative expertise to manage multi-disciplinary teams across multiple geographic sites to ensure that they retain focus on comprehensive approaches to chemical probe and lead generation. His expertise includes developing biochemical and cell-based assays employing methodologies across multiple technology platforms amenable to HTS. In his current role as Director of the HTS Center at Southern Research Institute, Dr. Bostwick oversees the screening of large compound libraries in biochemical and cell-based assays for both government and commercial clients. The state-of-the-art HTS Center is a suite of laboratories designed for efficient screening of large compound libraries while maintaining the capacity for a wide variety of assay types. Dr. Bostwick has authored and co-authored more than 25 scientific articles and has served on special emphasis review panels for the NIH.

Ashish K. Pathak

Dr. Pathak is an Advanced Research Scientist in Chemistry Department at Southern Research (SR). He received his Ph.D. in chemistry from University of Lucknow, Lucknow, India in 1993, after which he completed post-doctoral studies at Central Institute of Medicinal Aromatic Plants, Lucknow, India; National Institute of Health Sciences, Tokyo, Japan and Southern Research Institute, Birmingham, AL, USA in various aspects of phytochemistry, carbohydrates and medicinal chemistry. Dr. Pathak was an Assistant Professor of Organic Chemistry at Western Illinois University in Macomb, IL, for four years prior to rejoining Southern Research in 2009 as a principal investigator. He is also adjunct professor in Chemistry Department, University of Alabama at Birmingham (UAB) and member, Comprehensive Cancer Center, UAB. The primary research objective of Dr. Pathak’s laboratory is to execute medicinal chemistry approaches in various small molecule-based drug discovery programs, especially in the areas of infectious diseases (anti-virals and anti-bacterials), neurodegeneration and cancer. In addition, his lab is also developing natural products (Carbohydrates and Saponins)-based immune stimulants, vaccine adjuvants and drug delivery systems. These systems are based on products that are either semi-synthetic natural or are synthesized using natural scaffolds. The products can be used as stimulants for humoral and/or cellular immune responses in vaccines. He has worked in the area of antibacterials, especially in the area of glycosyltransfereases in Mycobacterium tuberculosis, anti-biofilm and peptidoglycan synthesis. He supervised several in-house and external small molecule drug discovery and probe generation programs such as in the area of Respiratory Syncytial Virus (RSV) and Influenza. Dr. Pathak has established the Highthroughput Parallel Synthesis laboratory at SR which is capable of producing large number of chemical libraries. The lab is involved in performing solution– and solid–phase parallel synthesis using state of the art robotic system and other synthetic equipment’s. His lab has developed a novel solution-phase ionic-liquid supported chemical synthesis/assembly based on phase-separated purification technique. This method is being exploited in synthesizing biologically relevant oligosaccharides as well as in combinatorial synthesis of small organic molecules in a high throughput process. Dr. Pathak has more than 120 publications, presentations and patents. Currently he is Project Leader of the Medicinal Chemistry Core of the AD3C CETR grant.

Mark J. Suto

Dr. Suto joined Southern Research in August 2011 as the Vice President of the Drug Discovery Division. He and his team focus on basic research and target identification and lead discovery and optimization of new therapies for cancer, infectious diseases and neurological diseases and disorders. He served as Vice President of Chemical and Pharmaceutical Sciences at Icagen Inc. from April 2004 until he joined Southern Research. From 2003 until 2004, Dr. Suto was Executive Vice President and Chief Scientific Officer of Neurion Pharmaceuticals, Inc., a California biotech company and from 1999 to 2002, Dr. Suto held senior management roles at DuPont Pharmaceuticals (acquired by Bristol-Myers Squibb Company) and Deltagen Research Laboratories, a subsidiary of Deltagen, Inc. Prior to DuPont Pharmaceuticals, Dr. Suto held management positions at CombiChem, Inc. and Signal Pharmaceuticals, Inc. and from 1982-1993, held positions of increasing responsibility in the Chemistry Department at Parke-Davis Pharmaceutical Research in Ann Arbor, Michigan. Dr. Suto received his Ph.D. and his Bachelor's degree in Medicinal Chemistry from the State University of New York at Buffalo.

He is a member of the American Chemical Society and has served on the Editorial Boards for several scientific journals, including Combinatorial Chemistry and High Throughput Screening, Investigational Drugs Section Editor, Expert Opinion in Drug Discovery, and Expert Opinion on Therapeutic Patents. He currently holds 41 U.S. Patents, and has three additional U.S. Patents pending.

Corinne E. Augelli-Szafran

Corinne E. Augelli-Szafran, Ph.D., has more than 25 years of practical and managerial experience in medicinal chemistry and drug discovery gained from leading research programs at institutions and pharmaceutical companies. Most recently, Dr. Augelli-Szafran was the Director of the Laboratory for Experimental Alzheimer Drugs (LEAD) at Harvard Medical School and Brigham and Women’s Hospital in Boston. In that position, she built a fully functional medicinal chemistry and drug discovery laboratory from the ground up which focused on the development of gamma-secretase Notch-sparing inhibitors for the therapeutic indication of Alzheimer’s disease. LEAD designed, synthesized, and tested internally more than 1,400 compounds which led to novel chemical series and lead compounds having better profiles than failed clinical candidates. Prior to LEAD, Dr. Augelli-Szafran spent 17 years at Parke-Davis Pharmaceutical Research and Pfizer Global Research and Development where she held a number of leadership roles investigating central nervous system therapeutics, with a major emphasis in Alzheimer disease therapeutics, but also in the areas of cardiovascular, atherosclerosis, psychotherapeutics and inflammation/pain. Some of her significant contributions at Parke-Davis and Pfizer were her project leadership roles in two key discovery programs where early stage hits and rationally designed targets were developed into several preclinical candidates that ultimately led to two development candidates for the treatment of Alzheimer’s disease in a four-year period and two development candidates as one potential dual agent for the treatment of both anxiety and inflammation/pain in a two-year period. Dr. Augelli-Szafran received a BA degree in Biology from the University of Pennsylvania, Philadelphia, PA, and MS and PhD degrees in Organic Chemistry from New York University, New York, NY. Her scientific record includes more than 140 publications, presentations and patents. She is a member of selected professional societies and a reviewer of articles for several journals. She has been an active committee member on the National Institutes of Health (NINDS) review panel for several years and also reviews grant applications for other groups such as the Michael J. Fox Foundation and the American Federation of Aging, of which she is a member of the National Scientific Advisory Council (NSAC). For many years, Dr. Augelli-Szafran was a faculty sponsor and host for the Harvard College Research Program in the Chemistry and Biochemistry Departments at Harvard University. She also was a faculty participant in the Harvard Graduate Women in Science/Engineering Mentoring Program since its inception in 2008 from which she was nominated for the Everett Mendelsohn Excellence in Mentoring Award in March 2010 and for the Mentor of the Year Award in 2012. She also served as scientific advisor for the 10th and 11th Annual World Pharma Congress ‘Successful Targeting of Alzheimer’s Disease’ meetings in 2011 and 2012. Dr. Augelli-Szafran has been invited to speak world-wide on her academic drug discovery research, she is an Adjunct Professor in the Bouve College of Health Sciences at the Center for Drug Discovery at Northeastern University in Boston, MA, and she consults for research and drug discovery programs to assist with the study of small molecules and to bring them forward into preclinical development as potential new therapies.

Babu Tekwani

Babu Tekwani, Ph.D., directs the Infectious Disease Department within Southern Research’s Drug Discovery Division. The department focuses on the disease-causing mechanisms and novel therapeutic and vaccine approaches for a diverse array of pathogens, with the objective of identifying novel mechanisms, targets and strategies for the prevention and treatment of protozoal, bacterial and viral infectious diseases throughout the world. Tekwani has spent more than 30 years researching tropical parasitic diseases such as malaria and leishmaniasis, vector-borne infectious diseases, and major global health threats. His work on new drug discovery for infectious diseases has identified potential new targets and sources for therapies against these diseases. Some of his most recent work focuses on developing a targeted drug delivery approach for a safer and more effective antimalarial therapeutic relative to currently used strategies against the disease for U.S. troops and global travelers. His research has been funded by the National Institute of Allergy and Infectious Diseases, the U.S. Department of Defense, and the U.S. Army Medical Research and Material Command. Prior to the appointment at Southern Research, Tekwani worked at the University of Mississippi for 18 years, where he served as Principal Scientist and Professor of Pharmacology at the School of Pharmacy’s National Center for Natural Products Research. Before joining the University of Mississippi in 2001, he worked as a senior scientist in the Biochemistry Division at the Central Drug Research Institute in Lucknow, India. He was awarded an international fellowship by the Fogarty International Center National Institute of Health and completed post-doctoral research training at the Milton S. Hershey Medical Center Penn State College of Medicine. Dr Tekwani is a Co-PI on Project 4: Identification and characterization of novel drugs that target the Influenza virus polymerase functions. He is responsible for developing in vitro phenotypic and target-based assays and screening compounds against influenza.

Jay A. Nelson

Jay A. Nelson, Ph.D. is a senior molecular virologist with over 190 papers and reviews on a variety of topics in virology and immunology. He has earned numerous awards and distinctions for his research. He has received Faculty Awards from the American Cancer Society, and he’s a Fellow of the American Academy of Microbiology. Dr. Nelson has served on multiple committees at the National Institutes of Health, American Cancer Society, and the American Foundation for AIDS Research. He was an editor for the Journal of Virology for 8 years and is currently an Associate Editor for PLOS Pathogens. Dr. Nelson is also the founder and Director of the Vaccine and Gene Therapy Institute (VGTI) at OHSU (http://www.ohsu.edu/vgti/) as well as VGTI-Florida Inc. in Port St. Lucie, FL (www.vgtifl.org/). Dr. Nelson was also the Director of Pacific Northwest Regional Centers of Excellence (PNWRCE) in Biodefense and Emerging Disease that is a consortium of investigators with extensive expertise and basic and translational research capacity directed at a broad range of NIAID Category A–C Priority Pathogens with an emphasis on flaviviruses including dengue virus, West Nile Virus, and Japanese Encephalitis Virus. The primary focus of Dr. Nelson’s research over the years has centered on the molecular pathogenesis and immune response to viruses including herpesviruses, flaviviruses and retroviruses. Dr. Nelson’s group has used molecular and animal model approaches over the past 30 years to characterize cytomegalovirus (CMV) and flavivirus replication. Some of these studies include analysis of mechanisms involved in HCMV latency and reactivation, the development of the first humanized mouse model to study HCMV latency, and the use of CMV as a viral vector for SIV with Louis Picker, M.D. and Klaus Frueh. Dr. Nelson’s group in collaboration with Alec Hirsch, Ph.D. used functional genomic approaches to determine that cYes, a cellular Src kinase, is an important regulator of flavivirus maturation. We have also shown that capsid interaction with cYes alters tight junction function by targeting degradation of Claudin 1 by the lysozome and have shown that WNV regulates the unfolded protein response (UPR) through CHOP to block cellular apoptosis. Dr. Nelson in collaboration with Dr. Hirsch and Dr. Klaus Frueh has developed a drug discovery program for flaviviruses and have identified several small molecule compounds that are currently being developed as potential drug candidates that is the focus of this project.

Michael S. Diamond

Michael Diamond received his M.D. and Ph.D. from Harvard University, and his post-doctoral and clinical training in infectious diseases and virology from the University of California, Berkeley and the University of California, San Francisco. He is currently a Professor of Medicine, Molecular Microbiology, Pathology & Immunology at Washington University School of Medicine and the Associate Director of the Center for Human Immunology and Immunotherapy Programs. His research focuses on the interface between viral pathogenesis and the host immune response with an emphasis on studying how novel innate immune response effector molecules restrict infection of multiple families of pathogenic human viruses.

Mark R. Denison

The Denison Lab studies the coronaviruses, a family of plus-strand RNA viruses that cause important infections in many animals and colds in humans. Dr. Denison has been an NIH-funded investigator in coronavirus replication, molecular biology, and cell biology for over 20 years. His lab was the first to discover that the coronavirus nonstructural protein 14 (nsp14), a 3’-to-5’ exoribonuclease (ExoN), was a powerful determinant of coronavirus high-fidelity replication. This work led to a highly-productive collaboration with the Baric lab demonstrating that SARS-CoV ExoN- viruses are attenuated, protective from lethal challenge, and do not revert to virulence under highly selective pressure. With their diverse expertise and technical resources, their groups are uniquely equipped to drive the development of coronavirus therapeutics from conception and validation into relevant animal models quickly and with a high probability for success. The continued emergence of coronaviruses into the human population, as very recently exemplified by HCoV-EMC in 2012, underscores the critical need for effective pan-coronavirus therapeutics. His lab has recently demonstrated that the resistance of MHV and SARS-CoV to the antiviral drug ribavirin requires the proofreading activity of ExoN. Loss of this activity confers profound sensitivity to ribavirin, and to the FDA-approved RNA mutagen 5-fluorouracil. These observations, combined with the conservation of ExoN among coronaviruses, demonstrate that small-molecule inhibitors of ExoN represent potent broadly applicable therapeutics to combat existing and emergent human coronaviruses.

Ralph Baric

The Baric laboratory uses genetic, immunologic, molecular and biochemical approaches to study the molecular mechanisms regulating virus replication, pathogenesis, molecular evolution and cross species transmission using emerging coronaviruses (Severe Acute Respiratory Coronavirus-SARS-CoV, Middle East Respiratory Coronavirus-MERS-CoV), flaviviruses (Dengue) and noroviruses as model systems. The SARS-CoV and MERS-CoV are emerging respiratory coronaviruses that most likely originated in bats and either circumvented the globe in 2003-04, or has caused an ongoing outbreak in the Middle East between 2012-2014, causing 10 or 40% mortality rates, respectively. The Baric group has pioneered new strategies for developing reverse genetic approaches for manipulating the SARS-CoV and MERS-CoV genomes, and are actively studying the role of two key viral genes, designated nsp16 2-0-methyltransferase (2MT) and the ExoN 3’ to 5’ exonuclease activity which is critical for viral transcription and RNA fidelity. As these genes play critical roles in disease severity and highly conserved across all Coronaviridae, ablation of the genetic activities of either gene attenuates viral pathogenesis, leading to universal genetic targets for live coronavirus vaccine design. In parallel, these gene functions are outstanding targets for the development of antiviral therapies against common, current and future emerging coronavirus strains in humans and animals. In this application, we identify small molecule inhibitors that block 2MT and ExoN activity of multiple coronaviruses, first in vitro and then in severe animal models of human disease. Dr. Baric is a professor in the Department of Epidemiology at the University of North Carolina, a World Technology Award Finalist, a member of the Biological Experts Science Group, a fellow of the American Association for Microbiology, a senior editor of Plos Pathogen, and a member of the editorial board of other specialty journals. His group has published over 200 papers, many in highly visible journals like PNAS, Nature Medicine, Science, and Plos Pathogens.

Daniel N. Streblow

The focus of the Streblow laboratory is on defining the role of human cytomegalovirus (HCMV) in the development of vascular disease and chronic rejection of organ allografts. The role of CMV in these diseases is still uncharacterized. Dr. Streblow's lab studies the following topics: 1) Determining the mechanisms of HCMV-accelerated vascular disease through identification of the viral genes expressed during these diseases using a HCMV microarray chip developed by Dr. Streblow's laboratory in combination with the Shared Microarray Core at VGTI. Once identified, the function of these viral genes will be examined using in vitro and in vivo models of CMV-accelerated vascular disease. 2) Determining the mechanisms of CMV-accelerated vascular disease in both mouse models of atherosclerosis and rat organ transplantation models using a DNA microarray approach. The Streblow lab in conjunction with Dr. Susan Orloff’s laboratory at OHSU has determined RCMV in vivo gene expression in infected rats and has begun functional studies of these genes. 3) Determining viral and host gene expression during the development of atherosclerosis and transplant vascular sclerosis, the vascular lesion associated with chronic allograft rejection. 4) Determining the mechanisms of viral acceleration of chronic allograft rejection from latently infected donors, which is the most common cause of HCMV-associated disease in transplant patients associated with expression during the different stages of viremia associated with CMV including. 5) Determining the function of CMV-encoded chemokine receptors in the context of viral pathogenesis and acceleration of vascular disease. Dr. Streblow was recently awarded an ONPRC pilot project grant to study Chikungunya in a NHP model.

Dr. Daniel Streblow received his B.S. in Pharmacology/Toxicology from the University of Wisconsin-Madison in 1992. He graduated from the University of Wisconsin-Madison with a Ph.D. in Viral Pathogenesis in 1997. Dr. Streblow received an NIH post-doctoral fellowship and worked with Dr. Jay A. Nelson in the Department of Molecular Microbiology and Immunology at Oregon Health & Science University. He is currently an Associate Scientist at the Vaccine and Gene Therapy Institute and Research Assistant Professor in the Department of Molecular Microbiology and Immunology.

Mark Heise

Dr. Mark Heise received his Ph.D. in Immunology from Washington University in St. Louis in 1996, and performed his postdoctoral training in molecular virology and viral pathogenesis at the University of North Carolina in Chapel Hill. Since 2000, Dr. Heise’s research has focused on viral pathogenesis, with an emphasis on using mouse models to understand how viruses interact with the host innate and adaptive immune system to impact the virus-induced disease process. His program combines expertise in molecular virology, immunology, and quantitative genetics, with the goal of using this expertise to identify and study novel viral and host genetic determinants that influence the pathogenesis of several important human pathogens, including Venezuelan equine encephalitis virus (VEEV) and chikungunya virus (CHIKV), influenza A virus (IAV), and MERS-CoV. In addition to studying the molecular mechanisms of viral pathogenesis, the Heise laboratory has also developed a number of mouse models of virus-induced disease as platforms for studying viral pathogenesis and for testing vaccines and therapeutics.

George R. Painter, PhD

Dr. Painter is the chief executive officer of Drug Innovation Ventures at Emory, LLC (DRIVE) and director of the Emory Institute for Drug Development (EIDD). He has twenty-four years of experience in the discovery and development of pharmaceutical agents, and most recently held the position of Executive Vice President, Research and Development, at Triangle Pharmaceuticals where he was a member of the founding management team. In addition to his management experience at Triangle Pharmaceuticals, Dr. Painter held positions at Burroughs Wellcome Co. beginning in 1983 including Director of Chemistry and Director of Virology. Subsequently, he served as Director of Research Process and International Deputy Therapeutic Head for Antiviral Research at Glaxo Wellcome Inc. Dr. Painter is a co-inventor of over forty-five patents, six of which have led to approved commercially available drugs or combinations of drugs for the treatment of HIV and hepatitis B. He has led international teams, which generated data for nine investigational new drug applications and three new drug applications. Dr. Painter earned a B.S. in chemistry, an M.S. in physical organic chemistry and a Ph.D. in synthetic chemistry from Emory University.

Dr. Frederick G. Hayden, MD, FACP serves as a Stuart S. Richardson Professor of Clinical Virology and Professor of Internal Medicine at the University of Virginia, School of Medicine. Dr. Hayden also serves as an Associate Director for Clinical Microbiology Laboratory (Virology) at the University of Virginia Health Sciences Center and Associate Director, Respiratory Disease Study Unit, The Center for the Prevention of Disease and Injury at the University of Virginia. He serves as Member of Scientific Advisory Board of IRX Therapeutics, Inc. Dr. Hayden served as Member of Senior Advisory Board of NexBio, Inc. and served as its Member of Advisory Board. He was a member of the Executive Committee for the NIAID - University of Alabama Collaborative Antiviral Study Group and the Board of Directors for the International Society for Antiviral Research. He has served as the editor for Antimicrobial Agents and Chemotherapy. He has also served on editorial boards for Antiviral Research, Antiviral Therapy, and the Journal of Antimicrobial Chemotherapy. He is an internationally recognized expert on respiratory viral infections and a leading clinical investigator on influenza antiviral agents. He focuses his research activities on the pathogenesis of respiratory viral infections and the application of antiviral agents for their prevention and treatment. The scope of his studies has ranged from antiviral mechanisms of action to clinical trials involving experimentally induced and naturally occurring infections. Dr. Hayden received the James H. Nakano Citation in 1996 from the Centers for Disease Control and Prevention. He is a board-certified in internal medicine and infectious diseases. Dr. Hayden holds a BA from Stanford University and an MD from Stanford University School of Medicine.

Top of Pag e

Pei-Yong Shi, PhD

Dr. Shi received a PhD in molecular virology from Georgia State University in 1995, and completed post-doctoral training in biochemistry at Yale University in 1998. He has been a research scientist at Bristol-Myers Squibb and the New York State Department of Health. He was senior unit head for the dengue unit at Novartis Institute for Tropical Diseases, Singapore from 2008-2010, and is currently the executive director for the disease biology unit at the Institute.