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.
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.
- 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).
- 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)