Department of Environmental, Agricultural and Occupational Health
College of Public Health and Associate Professor
Department of Pharmacology & Experimental Neuroscience
College of Medicine
University of Nebraska Medical Center
- 2007-present, Assistant Professor, Department of Pharmacology & Neuroscience, College of Public Health, College of Medicine, University of Nebraska Medical Center, Omaha, NE
- 2007-present, Assistant Professor, Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE
- 2006-2007, Research Assistant Professor; Marine Biomedicine and Environmental Sciences, Medical University of South Carolina
- 2005-2006, Research Assistant Professor; Pharmacology Department; Medical University of South Carolina
- 1998-2005, Assistant Professor; Pharmacology Department; Medical University of South Carolina
- 1991-1998, Research Assistant Professor; Pharmacology Department; Medical University of South Carolina
- 1987, PhD, Texas A&M University, College Station
- 1982, B.A. Biology and Chemistry, Southern Illinois University at Edwardsville
My research interests and training have been in the field of toxicology. Past research areas have involved the use of cell and whole animal models to study mechanisms of liver toxicity of drugs and environmental chemicals.
My present research interests lie in developing nanoformulations of antiretroviral drugs and testing these in cell-based and animal model systems. In collaboration with Dr. Howard Gendelman, we are developing long-acting nanoformulations of antiretroviral drugs for targeted and cell-based drug delivery for treatment of HIV-1 infection. The development of long-acting nanoformulations of antiretroviral drugs would simplify drug dosing regimens, extend dosing intervals, reduce unwanted drug side effects and improve drug penetration into viral sanctuary sites, thus reducing development of drug resistance. These nanoformulations can be specifically targeted to cells by coating them with targeting moieties for specific cell receptors. By targeting mononuclear phagocytes we hope to use these cells as vehicles for delivery of drug to sites that are normally inaccessible to antiretroviral drugs, specifically brain and lymph nodes. These cells can also serve as storage sites for the nanoformulated drugs, providing steady release of drug over an extended period of time and hence reducing drug doses and extending drug-dosing intervals. Our drug nanoformulations are first screened in macrophage-based assays for cell uptake, retention, release and efficacy against HIV-1 infection. Select nanoformulations are then tested in animal models for pharmacokinetics, biodistribution and efficacy against HIV-1 infection. To determine antiretroviral efficacy in mice, immune deficient mouse models reconstituted with human immune cells are used. These mice have been developed in the laboratories of Dr. Larisa Poluektova and Dr. Santhi Gorantla. Large animal pharmacokinetics of select nanoformulations are being determined in collaboration with Dr. Howard Fox’s laboratory. These studies are in anticipation of conducting preclinical safety assessment studies of specific antiretroviral drug nanoformulations that can be advanced to Phase I clinical trials.
- Nowacek, A.S., Balkundi, S., McMillan, J., Roy, U., Martinez-Skinner, A., Mosley, R.L., Kanmogne, G., Kabanov, A.V., Bronich, T., Gendelman, H.E. Analyses of nanoformulated antiretroviral drug charge, size, shape and content for uptake, drug release and antiviral activities in human monocyte-derived macrophages. J. Controlled Rel, 150: 204-211, 2011. PMCID: PMC3065529
- Kadiu, I., Nowacek, A., McMillan J., Gendelman, HE. Macrophage endocytic trafficking of antiretroviral nanoparticles. Nanomedicine, 6: 975-994, 2011. PMCID: PMC3184214
- Balkundi, S, Nowacek, AS, Veerubhotla, RS, Chen, H, Martinez-Skinner, A, Roy, U, Mosley, RL, Kanmogne, G, Liu, X, Kabanov, AV, Bronich T, McMillan J, Gendelman, HE. Comparative manufacture and cell-based delivery of antiretroviral nanoformulations. Int. J. Nanomedicine. 6: 3393-3404, 2011. PMCID: PMC3260033
- Roy, U, McMillan, J, Alnouti, Y, Gautum, N, Smith, N, Balkundi, S, Dash, P, Gorantla, S, Martinez-Skinner, A, Meza, J, Kanmogne, G, Swindells, S, Cohen, S, Mosley, RL, Poluektova, L, Gendelman, HE. Pharmacodynamic and antiretroviral activities of combination nanoformulated antiretrovirals in HIV-1-infected human PBL-reconstituted mice. J. Infect. Dis. 2012, 206:1577-1588. PMCID: PMC3570176
- Dash, PK, Gendelman, HE, Roy, U, Balkundi, S, Alnouti, Y, Mosley, RL, Gelbard, HA, McMillan, J, Gorantla, S, Poluektova, LY. Long-acting nanoformulated antiretroviral therapy elicits potent antiretroviral and neuroprotective responses in HIV-1 infected humanized mice. AIDS. 2012, 26:2135-2144. PMID: 22824628
- Gautam, N, Roy, U, Balkundi, S, Puligujja, P, Guo, D, Smith, N, Liu, X, Lamberty, B, Morsey, B, Fox, H, McMillan, J, Gendelman, HE and Alnouti, Y. Preclinical pharmacokinetics and tissue distribution of long-acting nanoformulated antiretroviral therapy. Antimicrob. Agents Chemother., 206: 1577-1588, 2013. PMCID: PMC3697338
- Puligujja, P, McMillan, J, Kendrick, L, Li, T, Balkundi, S, Smith, N, Veerubhotla, RS, Kabanov, A, Bronich, T, Gendelman, HE and Liu, X. Macrophage folate receptor-targeted antiretroviral therapy facilitates drug entry, retention, antiretroviral activities and biodistribution aiding in the elimination of human immunodeficiency virus infection. Nanomedicine: Nanotech. Biol. Med., 2013, Epub ahead of print. PMCID: PMC3779529
- McMillan, J. and Gendelman, H.E. Neuroimmune Cross Talk and HIV-Associated Neurocognitive Disorders. In: Neural-Immune Interactions in Brain Function and Alcohol Related Disorders, Vol. III, eds. Cui, C, Grandison, L, and Noronha, A, Springer, 2013.
- McMillan, J. Principles of Analytical Validation. In: Proteomic Profiling and Analytical Chemistry: The Crossroads, eds, Ciborowski, P, and Silberring, J, Elsevier, 2013.
- Society of Toxicology