Antiviral Pharmacodynamics Laboratory


Ashley Brown, Ph.D.Ashley Brown
Associate Professor
College of Medicine
Department of Medicine

Faculty Profile

The research focus of the antiviral pharmacodynamics laboratory is to design optimized therapeutic regimens for antiviral compounds active against viruses that pose a significant threat to global public health. Antiviral therapy plays a crucial role in the treatment of human infections caused by viral pathogens.  Successful antiviral therapy can lead to viral eradication in afflicted patients as well as preventing long-term complications that can arise from these infections.  In order for antiviral therapy to be maximally efficacious, the optimal dose and dosing interval for each compound must be elucidated.  Optimal dosage regimens are defined as regimens that maximize inhibition of viral replication, prevent the emergence and spread of drug-resistant viruses, and demonstrate minimal toxicity.  My laboratory utilizes an experimental approach that combines pharmacokinetic/pharmacodynamic (PK/PD) principles and state-of-the-art in vitro PD model systems with innovative mathematical models to intelligently design dosage regimens for antiviral compounds, either as monotherapy or combination chemotherapy. This approach yields valuable data that can be directly applied to human clinical trials, resulting in great potential to increase the likelihood of therapeutic success for new and existing antiviral agents.  Antivirals active against Influenza, HIV, hepatitis C, chikungunya, dengue, yellow fever, and Zika viruses have all been evaluated in my laboratory to date.

https://ufhealth.org/blog/qa-about-zika-virus-ashley-brown-phd


Funding

Current Projects

2018-2019            Investigator, Curza; “CZ-02 Pharmacodynamic Studies, A new Class of Antibiotics Selectively Inhibiting Bacterial Protein Synthesis”; P.I.: Dr. Arnold Louie, University of Florida; $687,272 total costs.

2017-2019            Principal Investigator, University of Florida Clinical Translational Science Institute Network Science Pilot Award; “The Development and Use of a Murine Aerosol Challenge Model for Influenza Infection to Optimize Anti-Influenza Therapeutic Regimens”; P.I.: Dr. Ashley N. Brown, University of Florida; $25,000

2014-2019            Principal Investigator, NIH/NIAID, 1 R01 AI111970; “Optimizing Combination Therapy for Hepatitis C virus with Pharmacodynamic Models”; P.I.: Dr. Ashley N. Brown, University of Florida; $5,595,362 total costs.

2015 – 2020         Co-Investigator, NIH/NIAID R01AI121430; “Rapid Identification of Optimal Combination Regimens for Pseudomonas aeruginosa”; P.I.: Dr. George L. Drusano, $3,705,212 total costs.


Funding

Completed Projects

2014-2018            Principal Investigator, Gatorade Pilot Program/University of Florida; “Identifying Optimal Dosing Strategies for Antivirals Active against Dengue virus using a Novel In Vitro Pharmacodynamic Model System”; P.I.: Dr. Ashley N. Brown, University of Florida; $130,000 total costs.

2015-2018            Principal Investigator, Gatorade Drug Development funding/University of Florida in collaboration with Cloud Pharmaceuticals; “Structure-Based Discovery of Dengue Virus Protease Inhibitors”; P.I.:Dr. Ashley N. Brown, University of Florida.

2017-2018            Principal Investigator, Florida Department of Health; “Identification of Antiviral Therapies for the Treatment of Zika Virus using Existing Drugs”; P.I.: Dr. Ashley N. Brown, University of Florida; $1,140,922 total costs.

2015-2017            Principal Investigator, NIH/NIAID/AIDS Clinical Trials Group (ACTG); “Preclincal Studies to Determine Optimized Dosing of Oxazolidinones for the Treatment of Tuberculosis (TB)”; P.I.: Dr. Ashley N. Brown, University of Florida; $265,000 total costs.

2013-2014            Co-Principal Investigator, NIH/NIAID/Miriam Hospital (00102292); “Lifespan/Tufts/Brown Center for AIDS Research (CFAR) Mathematical Analysis of Drug Interaction for TB and HIV”; P.I.: Dr. George L. Drusano, University of Florida; $275,050 total costs.

2011-2013            Principal Investigator, Merck & Co., Inc.; “Determination of the Pharmacodynamically-linked Index for Two Integrase Inhibitors”; P.I.: Dr. Ashley N. Brown, University of Florida; $360,947 total costs.

2008-2013            Co-investigator, NIH/NIAID, 1 R01 AI 079729-01; “Resistance Suppression for Influenza virus with Combination Chemotherapy”; P.I.: Dr. George L. Drusano, Ordway Research Institute; $2,283,822 total costs


Students and Trainees

Current

Evelyn Franco, Pharm.D. (Ph.D. student)

Past

Karen Gallegos, Ph.D. (postdoctoral associate)
Camilly Pires de Mello, Ph.D. (postdoctoral associate)


Published Manuscripts

(Last 5 years)

Franco, E.J., J.L. Rodriquez, J.J. Pomeroy, K.C. Hanrahan, and A.N. Brown (2018). The Effectiveness of Antiviral Agents with Broad-Spectrum Activity against Chikungunya Virus Varies Between Host Cell Lines. Antivir. Chem. Chemother. 26: 1-7.

Pires de Mello, C.P., X. Tao, M. Vicchiarelli, J.B. Bulitta, A. Kaushik, and A.N. Brown (2018).  Clinical Regimens of Favipiravir Inhibit Zika Virus (ZIKV) Replication in the Hollow Fiber Infection Model (HFIM) System.  Antimicrob. Agents Chemother. 62:e00967-18.

Pires de Mello, C.P., G.L. Drusano, J.L. Rodriquez, and A.N. Brown (2018).  Antiviral Effects of Clinically-Relevant Interferon-α and Ribavirin Regimens against Dengue Virus (DENV) in the Hollow Fiber Infection Model (HFIM) System.  Viruses. 10:317.

Kaushik, A., A. Yndart, S. Kumar, R.D. Jayant, A. Vashist, A.N. Brown, C-Z. Li, and M. Nair (2018).  A Sensitive Electrochemical Immunosensor for Label-Free Detection of Zika-virus Protein.  Sci Reports. 8:9700.

Ande, A., T. Vaidya, B.N. Tran, M. Vicchiarelli, A.N. Brown, and S. Ait-Oudhia (2018). Utility of a Novel Three Dimensional and Dynamic (3DD) Cell Culture System for PK/PD Studies: Evaluation of a Triple Combination Therapy at Overcoming Anti-HER2 Treatment Resistance in Breast Cancer.  Front. Pharmacol. 9:403.

Pires de Mello, C.P., X. Tao, T-H. Kim, J.B. Bulitta, J.L. Rodriquez, J.J. Pomeroy, and A.N. Brown (2018).  Zika virus (ZIKV) Replication is Substantially Inhibited by Novel Favipiravir and Interferon-alpha Combination Regimens. Antimicrob. Agents Chemother. 62:e01983-17.

Pires de Mello, C.P., G.L. Drusano, J.R. Adams, M. Shudt, R. Kulawy, and A.N. Brown (2018). Oseltamivir-Zanamivir Combination Therapy Suppresses the Amplification of Drug-Resistant H1N1 Influenza A viruses in the Hollow Fiber Infection Model (HFIM) System. Eur J Pharm Sci. 111: 443-449.

Brown, A.N., L. Liu, J.L. Rodriquez, L. Zhao, L. Schuster, E. Li, G.P. Wang, M.N. Neely, W. Yamada, and G.L. Drusano (2017).  Sofosbuvir (SOF) Suppresses Ledipasvir (LDV)-resistant Mutants during SOF/LDV Combination Therapy against Genotype 1b Hepatitis C Virus (HCV). Sci Reports. 7:14421.

Pomeroy, J.J., G.L. Drusano, J.L. Rodriquez, and A.N. Brown (2017). Searching for Synergy: Identifying Optimal Antiviral Combination Therapy Using Hepatitis C Virus (HCV) Agents in a Replicon System. Antiviral Res. 146, 149-152.

Fleisher, B., A.N. Brown, and S. Ait-Oudhia (2017). Application of Translational Pharmacometrics and Quantitative Systems Pharmacology to Cancer Therapy: The Example of Luminal A Breast Cancer. Pharmacol Res. 124, 20-33.

Brown, A.N., K.M. Gallegos, D.Z. D’Argenio, and G.L. Drusano (2017). Reply to Scagnolari et al. J. Infect. Dis. 215, 493-494.

Gallegos, K.M., G.L. Druasno, D.Z. D’Argenio, and A.N. Brown (2016). Chikungunya Virus: In Vitro Response to Combination Therapy with Ribavirin and Interferon Alfa 2a. J. Infect. Dis. 214, 1192-1197.

Brown, A.N., G.L. Drusano, J.R. Adams, J.L. Rodriquez, K. Jambunathan, D.L. Baluya, D.L. Brown, A. Kwara, J.C. Mirsalis, R. Hafner, and A. Louie (2015).  Preclinical Evaluations to Identify Optimal Linezolid Regimens for Tuberculosis Therapy.  mBio 6(6):e01741-15.

Brown, A.N., J.R. Adams, D.L. Baluya, and G.L. Drusano (2015). Pharmacokinetic Determinants of Virological Response to Raltegravir in the In Vitro Pharmacodynamic Hollow Fiber Infection Model (HFIM) System.  Antimicrob. Agents Chemother. 59, 3771-3777.

 

Complete List of Published Work in MyBibliography:

https://www.ncbi.nlm.nih.gov/sites/myncbi/1FaMeeLFsunQp/bibliography/47883414/public/?sort=date&direction=ascending