Barry J. Margulies

Research Interests

The Towson University Herpes Virus Lab has three main research foci.

Current antiviral therapy for the human herpes viruses, HSV–1, –2, and varicella zoster virus and the feline herpesvirus, FHV-1, consists of multiple doses of FDA-approved anti-herpetic drugs (typically acyclovir [ACV], valacyclovir, penciclovir [PCV], or famciclovir) taken daily for the lifetime of the host. These daily doses require rigorous patient compliance; missed doses allow small windows of drug troughs that permit breakout replication, sometimes resulting in drug-resistant mutants. Our research involves slow, controlled release of ACV from both biodegradable non-biodegradable polymer matrices. These devices release continuous, steady levels of drug for an estimated 2 months to 5 years after a single implantation, depending on the engineered configuration. We are continuing to explore the chemistry, biology, pharmacology, and engineering of these implants to further improve their design and eventual clinical deployment in human patients.

Human cytomegalovirus encodes four chemokine receptor-related proteins. Of these, the one encoded by US27 appears to bind GABARAP, a host protein involved in autophagy. Current experiments, in collaboration with labs at Texas Woman’s, The Cleveland Clinic, and the University of Maryland, Baltimore are geared toward better understanding these interactions at a molecular level and determining their importance with respect to evading host immune defenses against herpesvirus infection.

We are also exploring the functional lifetime of HSV-1 and HSV-2 on fomites, inanimate objects that may serve as transmission vehicles for these viruses. We are conducting quantitative analysis of how long each virus survives given different surfaces, different humidity levels, and different time spans.

Biography

Dr. Margulies received B.S. at the Massachusetts Institute of Technology, where he did research with Drs. Eyal Ron and Robert Langer in controlled release technology. He earned his Ph.D. at the Johns Hopkins University School of Medicine under the tutelage of Dr. Wade Gibson, where he studied the G protein-coupled receptors encoded by human cytomegalovirus. He did his post-doctoral studies also at the Johns Hopkins University School of Medicine, with Dr. Janice Clements, studying CD4-independent entry of human and simian immunodeficiency viruses.  He has been a faculty member at Towson University since 2001, where he established the Towson University Herpes Virus Lab. His research encompasses studies in the molecular biology of human cytomegalovirus and human herpes virus–6, and new methods for the long-term prevention of recurrent outbreaks of herpes simplex viruses-1 and -2, varicella zoster virus, and feline herpes virus-1.

Selected Publications

• Margulies, B.J., Browne, H., and W. Gibson. Identification of the Human Cytomegalovirus G Protein- Coupled Receptor Homologue Encoded by UL33 in Infected Cells and Enveloped Virus Particles. Virology 225:111-125 (1996).
• Edinger, A.L., Margulies, B.J.*, Mankowski, J.L.*, Doranz, B.J.*, Lee, B.*, Rucker, J., Sharron, M. Hoffman, T.L., Berson, J.F., Zink, M.C., Hirsch, V.M., Clements, J.E., and R.W. Doms (*equal contributors). CD4-Independent, CCR5-Dependent Infection of Brain Capillary Endothelial Cells by a Neurovirulent Simian Immunodeficiency Virus Strain. Proc Natl Acad Sci USA 94:14742-14747 (1997).
• Margulies, B.J., and W. Gibson. The Chemokine Receptor Homologue Encoded by US27 of Human Cytomegalovirus is Heavily Glycosylated and Is Present in Infected Human Foreskin Fibroblasts and Enveloped Virus Particles. Virus Res 123:57-71 (2007).
• Johnson, T.P,. Frey, R., Modugno, M., Brennan, T.P., and B.J. Margulies. Development of an Acyclovir Implant for the Long-Term Control of Herpes Simplex Virus Infection. Int J Antimicrob Agents 30:428- 435 (2007).
• Berkower, C.L., Johnson, N.M., Longdo, S.L., McGusty-Robinson, S.O., Semenkow, S.L., and B.J. Margulies. Silicone-Acyclovir Controlled Release Devices Suppress Primary Herpes Simplex Virus-2 and Varicella Zoster Virus Infections In Vitro. Adv Pharmacol Sci 2013:915159 (2013).
• Semenkow, S.L., Johnson, N.M., Maggs, D.J., and B.J. Margulies. Controlled Release Delivery of Penciclovir via a Silicone (MED-4750) Polymer: Kinetics of Drug Delivery and Efficacy in Preventing Primary Feline Herpesvirus Infection in Culture. Virology J 11:34 (2014).
• Stegman, J.R., Badin, J.K., Biles, K.A., Etienne, T., Fartash-Naini, S., Gordon, A.B., Greeley, Z.W., Harding, B.W., Mack, R.J., Masica, D., Nelson, A.N., Samra, A.K., Smith, S.E., Thomas, G.P., Zack, H., Brunker, T.J., and Margulies, B.J. Volatile acid-solvent evaporation (VASE): molecularly homogeneous distribution of acyclovir in a bioerodable polymer matrix for long-term treatment of herpes simplex virus-1 infections. J Drug Delivery 2018:6161230 (2018).
• Covert, J.C., Thomasy, S.M., Kado-Fong, H., Kon, L.N. Kass, P.H., Reilly, C.M., Lappin, M.R., Margulies, B.J., and D.J. Maggs. Exploratory study of the safety and tolerability of a subconjunctival penciclovir implant in cats experimentally infected with herpesvirus. J Ocular Pharmacol Therapeutics 35:1-12 (2019).
• Giannasca, N.J., Suon, J.S., Evans, A.C., and B.J. Margulies. Matrix-based controlled release delivery of acyclovir from poly (ethylene co-vinyl acetate) rings. J Drug Deliv Sci Tech 55:101391 (2020).
• Greeley, Z.W., Giannasca, N.J., Porter, M.J., and B.J. Margulies. Acyclovir, cidofovir, and amenamevir have additive antiviral effects on herpes simplex virus type 1 in cell culture systems. Antiviral Res. 176:104754 (2020).
• Sadowki, L.A., Upadhyay, R., Greeley, Z.W., and B.J. Margulies. Current Drugs to Treat Infections with Herpes Simplex Viruses-1 and -2. Viruses. 13:1228 (2021).
• Sadowki, L.A., Lesko, G.M., Suissa, C., Upadhyay, R., Desai, P.J., and B.J. Margulies. Plaquing of Herpes Simplex Viruses. J Vis Exp. 177:62962 (2021).
• Margulies, B.J. The World of Antiherpetic Vaccines and Drugs, 2022. Viruses. 14:850 (2022).

Products

Patents Pending

• T.P. Johnson and B.J. Margulies. Long-Term Suppression of Herpesvirus Infection (provisional #60805381, 2006; pending #11/766,298, 2007)
• B.J. Margulies, J.K. Badin, Fartash-Naini, S., T. Etienne, S. Fargis, A. Samra. Biodegradable Subcutaneous Implants and Method of Making (pending #14/199,010, 2014)