Mackenzie Cottrell, Pharm.D., M.S. is a research assistant professor in the Division of Pharmacotherapy and Experimental Therapeutics. Her research focuses on describing pharmacokinetic/pharmacodynamic relationships in mucosal tissues for antiretrovirals being used in HIV prevention and cure interventions.
Angela Kashuba Lab
Angela Kashuba Lab
Now Accepting Doctoral Canidates
Welcome to the UNC School of Pharmacy Clinical Pharmacology and Analytical Chemistry Laboratory web site! Our faculty and staff facilitate research in preclinical and clinical pharmacology and analytical chemistry in pursuit of a common goal: optimizing the prevention and treatment of HIV infection. We invite you to learn more about our vigorous research agenda. You are welcome to contact us for further information on our activities and services. We also encourage you to visit the UNC Center for AIDS Research website and our Clinical Pharmacology and Analytical Chemistry Core website.
Current Research Projects
The Kashuba lab is engaged in a number of research projects. Current studies include the following sponsored research:
- Ronald Swanstrom, Principal Investigator; Kashuba ADM, Core Director; Cottrell M, Investigator. UNC Center for AIDS Research Core E: Clinical Pharmacology/Analytical Chemistry.The Clinical Pharmacology/Analytical Chemistry Core of the UNC CFAR is designed to provide a centralized facility to advise, support and perform pharmacological and analytical studies of AIDS related clinical and basic science research projects. Projects range from in-vitro correlations of drug disposition, drug interactions and drug toxicity to clinical pharmacokinetic-dynamic evaluations of interactions, efficacy, toxicity and the development of drug resistance. NIAID P30-AI50410-20; 08/01/11 – 07/31/21; $206,195.
- Buse, Principal Investigator; Kashuba ADM, Mentor. North Carolina Translational & Clinical Sciences Institute (NC TraCS). This grant provides 5 years of support for UNC’s CTSA award, the NC Translational and Clinical Sciences (TraCS) Institute. Dr. Kashuba serves within the Education Program of the NC TraCS Institute and mentors KL2 Scholars. NIH 5UL1TR001111-05; 05/01/2016- 04/30/2018; salary support.
- Kashuba ADM, Principal Investigator.Multi-Species Mechanisms of Drug Bio-distribution in HIV Tissue Reservoirs. This project aims to identify what species differences and pharmacologic barriers exist in extracellular and intracellular antiretroviral biodistribution and efficacy in eliminating active HIV reservoirs. NIH/NIAID 1R01AI111891-04 3/15/2014-2/28/2019 $519,821.
- Boggess, Principal Investigator; Kashuba ADM, Research Director. UNC Building Interdisciplinary Research Careers in Women’s Health (K12). Kashuba will serve as Associate Research Director and Resource Laboratory Network Director for this K12 project. NIH 2K12HD001441-18; 9/30/2015 – 7/31/2020; $35,550.
- Kashuba ADM, Principal Investigator. Novel Mass Spectrometry Imaging Methods to Quantify Antiretroviral Adherence. It is important to identify if someone is taking a medication regularly and as prescribed to optimize their health and wellbeing. Sometimes, patients have trouble remembering if and when they miss doses; other times, even though patients are taking their medication, it is not getting into the body in the right amount. Quickly monitoring medications in 5-10 hair strands using our novel imaging technology called IR-MALDESI will allow patients and their doctors to see how much medication they are exposed to over 1 or more months, and help identify challenges to taking medication in both research and clinical settings. This proposal will optimize and explore the acceptability and feasibility of using IR-MALDESI for monitoring medications in hair. NIH/NIAID; 01/01/2016-12/31/2020; $711,764.
- Margolis, Principal Investigator; Kashuba ADM,Project Leader; Cottrell M, Investigator. Collaboratory of AIDS Researchers for Eradication (CARE). Including scientists from leading universities and Merck Research Laboratories, Qura Therapeutics, and Macrogenics, the Collaboratory of AIDS Researchers for Eradication (CARE) will seek to eradicate HIV infection by developing and testing therapies that will permanently destroy the viral reservoir. NIH 1UM1AI126619-02; 7/14/2016 – 6/30/2021; $66,750.
- Lewin, Principal Investigator; Kashuba ADM, Consortium PI. Long term persistence of HIV in the liver and the clinical impact on HIV-HBV co-infection. One of the main challenges in the management of HIV is that it has long lived forms that persist in the face of antiviral therapy. Several studies suggest that the liver may be a reservoir of HIV even on long term ART. To determine whether HIV persistence in the liver on ART is a consequence of sub therapeutic levels of ARV in liver, as previously described for lymphoid tissue and rectal tissue, we propose to measure ARV levels in human liver, plasma and PBMC samples both pre and following at least 2 years ART by both LC-MS/MS and IR-MALDESI IMS methods. NHMRC/University of Melbourne 1101836IPF 16-4433; 11/28/2016 – 12/31/2019; $32,805.
- Cottrell M, Principal Investigator. Animal Model for Testing SIV Latency Reversal Strategies. The UNC Clinical Pharmacology and Analytical Chemistry Laboratory will develop and validate Romedepsin and prostratin analytical methods in plasma and tissues for the overall project. Furthermore, therapeutic dosing strategies will be designed and developed for these compounds and perform pharmacokinetic analysis, modeling and simulation using the resulting concentration data. SubAward 0047867(126557-1)/5R01AI119346 (Apetrei); 8/1/2015-1/31/2019; $50,888/4 years.
- Cottrell M, Principal Investigator. Differential HIV infection and Tenofovir activity in pre- and post-menopausal women. The UNC Center for AIDS Research Clinical Pharmacology and Analytical Chemistry Laboratory will be providing tenofovir and tenofovir diphosphate concentration analysis on surgery-derived tissue explants and clinical biopsy samples. SubAward S120282-3/4R01HD072705-05 (Doncel); 6/1/2016-5/31/2018; $43,815.
- Cottrell M, Principal Investigator. Intramuscularly Administered TMB 607 in HIV Negative Volunteers. This project will develop an analytical method for determination of concentration of TMB-607 in human plasma. TaiMed Biologics, Inc. Contract AGR#A16-1466-001; 5/26/2016-5/25/2019; $22,646.
- Cottrell M, Principal Investigator. Pharmacokinetics Testing for CONRAD A15-137, titled Exploratory Pharmacokinetic and Pharmacodynamic Study of Oral F/TAF for the Prevention of HIV UNC laboratory will perform pharmacokinetic (PK) analysis on de-identified samples collected under CONRAD A15-137 study with UNC for the purpose of sample analysis and PK analysis including the provision of input into the statistical analysis plan, manuscript and other appropriate PK analyses reports. USAID SubAward MAPS1-17-073/AID-OAA-A-14-00011 (MAPS1); 3/15/2017-4/14/2018; $605,946.
- Cottrell M, Principal Investigator. Chimerix CMX048 Feasibility_Work Order#2. UNC laboratory will perform Optimization IR-MALDESI assay for a single compound, CMX16792 (CMX8521-PPP), in gut tissue and assessment of lower limit of quantitation that can be achieved for the analysis of CMX16792 in gut tissues. Chimerix, Inc., Award PO#WP100215; 6/28/2017-12/27/2017; $4,893.
- Cottrell M, Principal Investigator. Work Order 3_Evaluation of sulfolane and 3-nitrobenzyl alcohol on signal for CMX048 and Evaluation of sensitivity and linearity of CMX048 in PBMC lysate. UNC laboratory will perform the work of this project. Chimerix, Inc., Award PO#WP100405; 10/02/2017-4/01/2018; $7,466.
- Cottrell M, Investigator. The University of North Carolina for AIDS Research. The UNC CFAR is notable for the breadth of research activity, the high level of excellence of it member researchers, and the importance of its domestic and international partners in fighting the HIV epidemic. NIH; 2P30AI050410-19; 8/1/2016–7/31/2021; $7,466.
- Cottrell M, Investigator. Collaboratory of AIDS Researchers for Eradication. The Collaboratory of AIDS Researchers for Eradication (CARE) will seek to eradicate HIV infection by developing and testing therapies that will permanently destroy the viral reservoir. NIH/NIAI; 1UM1AI126619-01; 7/14/2016-6/30/2021; $18,356.
- Cottrell M, Project Lead. Qura Project 1F Using a Novel Hollow Fiber Model System to Predict the In Vivo Pharmacodynamics of Latency Reversing Agents. One of the most advanced investigational strategies to eradicate HIV has been termed “Kick and Kill”. The “Kick” refers to using latency reversing agents (LRAs) to induce viral transcription from latently infected cells. In this study, we apply a model of HIV latency to the hollow fiber culture system, and determine if it can reproduce the clinical trial results of daily and intermittent LRA dosing. In achieving the aims of this project, we will establish proof of concept that this novel hollow fiber model of HIV latency can predict in vivo pharmacodynamics for LRAs. Qura Therapeutics, LLC; 1/01/2017 – 12/31/2017; $82,519.
- Wira, Principal Investigator; Cottrell M, Consortium PI. Chemical Contraceptive Control of Microbicides in the Female Reproductive Tract. Dr. Kashuba’s lab will pharmacokinetic analysis expertise and utilize bioanalytical methods developed for parent and intracellular active metabolites in tissue and cellular matrices in the female genital tract. NIH/Dartmouth College, 1R01AI117739-02; 2/01/2015 -1/31/2018; $64,096.
The role of menopause in tenofovir diphosphate and emtricitabine triphosphate concentrations in cervical tissue. Nicol MR, Brewers LM, Kashuba AD, Sykes C. AIDS. 2018 Jan 2;32(1):11-15. PubMed PMID: 29112071.
Validation of an LC-MS/MS assay to simultaneously monitor the intracellular active metabolites of tenofovir, emtricitabine, and lamivudine in dried blood spots. Schauer AP, Sykes C, Cottrell ML, Prince H, Kashuba ADM. J Pharm Biomed Anal. 2017 Oct 31;149:40-45. PMID: 29100029; PubMed Central PMCID: PMC5741486. (Add hyperlink: https://www.ncbi.nlm.nih.gov/pubmed/?term=29100029)
Tissue Pharmacologic and Virologic Determinants of Duodenal and Rectal Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution in HIV-Infected Patients Initiating Antiretroviral Therapy. Asmuth DM, Thompson CG, Chun TW, Ma ZM, Mann S, Sainz T, Serrano Villar S, Utay NS, Garcia JC, Troia-Cancio P, Pollard RB, Miller CJ, Landay A, Kashuba AD. J Infect Dis. 2017 Oct 17;216(7):813-818. PMID: 28968888.
Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency. Archin NM, Kirchherr JL, Sung JA, Clutton G, Sholtis K, Xu Y, Allard B, Stuelke E, Kashuba AD, Kuruc JD, Eron J, Gay CL, Goonetilleke N, Margolis DM. J Clin Invest. 2017 Aug 1;127(8):3126-3135. PMID: 28714868. PMCID: PMC5531421.
A spatio-temporal assessment of simian/human immunodeficiency virus (SHIV) evolution reveals a highly dynamic process within the host. Feder AF, Kline C, Polacino P, Cottrell M, Kashuba ADM, Keele BF, Hu SL, Petrov DA, Pennings PS, Ambrose Z. PLoS Pathog. 2017 May 25;13(5):e1006358. PMID: 28542550. PMCID: PMC5444849.
Co-trimoxazole Prophylaxis, Asymptomatic Malaria Parasitemia, and Infectious Morbidity in Human Immunodeficiency Virus-Exposed, Uninfected Infants in Malawi: The BAN Study. Davis NL, Wiener J, Juliano JJ, Adair L, Chasela CS, Kayira D, Hudgens MG, van der Horst C, Jamieson DJ, Kourtis AP; Breastfeeding, Antiretrovirals and Nutrition (BAN) Study Team; Breastfeeding, Antiretrovirals and Nutrition (BAN) Study Team. Clin Infect Dis. 2017 Aug 15;65(4):575-580. PMID: 28444232.
Predicting HIV Pre-exposure Prophylaxis Efficacy for Women using a Preclinical Pharmacokinetic Pharmacodynamic In Vivo Model. Wahl A, Ho PT, Denton PW, Garrett KL, Hudgens MG, Swartz G, O’Neill C, Veronese F, Kashuba AD, Garcia JV. Sci Rep. 2017 Feb 1;7:41098. PMID: 28145472. PMCID: PMC5286499.
Elvitegravir concentrations in seminal plasma in HIV-1-infected men. Imaz A, Niubó J, Kashuba AD, Ferrer E, Sykes C, Rozas N, Acerete L, Vila A, Podzamczer D. HIV Med. 2017 Mar;18(3):225 230. doi: 10.1111/hiv.12417. Epub 2016 Aug 1. PMID: 27477062.
CPAC VALIDATES NOVEL ASSAY TO MEASURE ANTIRETROVIRALS IN DRIED BLOOD SPOT FOR ADHERENCE MONITORING
The Clinical Pharmacology Core has recently developed and validated a sensitive, multiplex LC-MS/MS assay to measure the intracellular metabolites of the 3 most commonly prescribed NRTIs (tenofovir, emtricitabine, and lamivudine) in dried blood spots collected from patients on therapy. This assay allows investigators to monitor adherence in clinical trials with the convenience of dried blood spot sampling, storage and shipping. The addition of lamivudine, which is generically available, opens up opportunity for international investigations. Our methods and findings are in press in the Journal of Pharmaceutical and Biomedical Analysis (Schauer et al. Validation of an LC-MS/MS Assay to Simultaneously Monitor the Intracellular Active Metabolites of Tenofovir, Emtricitabine, and Lamivudine in Dried Blood Spots. JPBA. In press).
Dr. Kashuba’s research focuses on the clinical pharmacology of drugs used in the treatment, prevention, and cure of HIV infection. She is working on optimizing dosing strategies for HIV prevention including the role of sex and ethnicity, characterizing drug distribution in putative viral reservoirs using mass spectrometry imaging, determining predictors of drug tissue distribution, and developing in vitro models for optimizing combination therapy for HIV cure.
Dr. Rosen’s research focuses on the development of methods to measure intracellular distribution of therapeutics and their metabolites in a variety of biological matrices using mass spectrometry imaging. He is currently quantifying the penetration of drugs relevant to HIV treatment and eradication into putative viral reservoirs, and combining this approach with traditional imaging modalities to evaluate efficacy of experimental treatment regimens.
Prince joined the lab in 2008. She holds an AS and BA in Microbial Genetics from Peace College, and an MPA from Eastern Virginia Medical School. She has completed post-graduate surgical training at Eastern Virginia Medical School, Emory University, Harvard University and John Hopkins University. She is a Certified Clinical Research Professional who oversees all clinical aspects of research studies, from protocol development to implementation and patient care.
White has been an outstanding analytical chemist at UNC since 1994, and she has received awards in recognition of her exceptional service. White oversees analytical methods and standard operating procedures in the laboratory.
The Kashuba laboratory has been supporting academic and pharmaceutical industry fellows since 1997.
- HIV Clinical Pharmacology Academic Fellowship brochure
- Pharmaceutical Industry Fellowship brochure
The Kashuba laboratory is a place where graduate education is supported and nurtured.
- Graduate program brochure
Erin Burgunder is a graduate student in the Division of Pharmacotherapy and Experimental Therapeutics. She joined the lab in 2016. Burgunder is focused on the penetration of antiretroviral drugs into reservoir tissues, an area of interest for HIV cure. Her research investigates biological and pharmacokinetic factors affecting antiretroviral efficacy in lymph nodes.
Aaron Devanathan, PharmD is a graduate student in the Division of Pharmacotherapy and Experimental Therapeutics after having completed residency training at UNC Hospitals. Devanathan is focused on the distribution of antiretroviral drugs within active HIV reservoirs, an area of interest towards a cure. His research aims to visualize, quantify, and model the interspecies pharmacokinetics of antiretroviral therapy within the spleen tissue.
Talisa graduated with a B.S. in Chemistry & Mathematics and has spent the past few years optimizing processes through efficient instrumentation usage in environmental, pharmaceutical and molecular research laboratories while working at BUCHI Analytical. She is currently focused on PK/PD modeling of latency reversing agents being used in HIV cure interventions.
Melanie Nicol, PhD, 2009-2014
Assistant Professor, University of Minnesota School of Pharmacy
Michael Cohen-Wolkowiez, PhD, 2007-2012
Associate Professor of Pediatrics, Duke University School of Medicine
Naser Rezk, MS, 2002-2007
Mary Peace McRae, PharmD, PhD, 2001-2005
Assistant Professor, Kansas City University
Corbin Thompson, PharmD
Daijha J. C. Anderson, PharmD, RPh
Mac Gilliland, PhD
Kirsten Moody, PharmD
Brian Maas, PharmD
Mike Weber, PharmD
Mackenzie Cottrell, PharmD
Elizabeth Andrews, PharmD
Christine Trezza, PharmD
Research Scientist, ViiV
Tanja Hadzic, PhD, 2012-2014
Manager, Medical Affairs, Salix Pharmaceuticals
Ben Greener, PharmD, 2011-2013
Jessica Adams, PharmD, 2010-2012
Assistant Professor, University of Sciences, Philadelphia
Racheal Kendrick, PharmD, 2009-2011
Pharmacokineticist II, Quintiles, Kansas
Kevin Brown, PharmD, 2007-2010
Pharmacist, UNC Hospitals
Amanda Jenkins, PharmD, 2008-2010
Research Scientist, United Therapeutics
Sunita Paul, MS, 2007-2008
Clinical Research Manager, New York
Kan Lu, PharmD, 2006-2008
Postdoctoral Research Fellow, UCLA
Julie Dumond, PharmD, 2005-2007
Assistant Professor, UNC Eshelman Schoolof Pharmacy
Manoli Vourvahis, PharmD, 2005-2007
Manager, Pfizer, Inc., Clinical Pharmacology, Infectious Disease, New London, CT
Hiba Tappouni, PharmD, 2004-2006
Principal Clinical Research Scientist, Neurosciences CPDM, GlaxoSmithKline, RTP, NC
Ya-Chi Chen, PharmD, 2003-2005
Senior Pharmacologist, Daichi Pharmaceuticals
Rosa Yeh, PharmD, 2003-2005
Director, Pharmacokinetics Laboratory, SeattleCancer Care Alliance, Seattle, WA
Jennifer Park, PharmD, 2002-2004
Clinical Research Program Manager, GlaxoSmithKline
Leslie Davidson, PharmD, 2002-2004
Esam Hamed, MD, 2009-2014
Amanda Corbett, PharmD, 2001-2003
Clinical Assistant Professor, UNCEshelman Schoolof Pharmacy
Michael Lim, PharmD, 2001-2003
Oncology Medicine Development Centre, GlaxoSmithKline
Sunila Reddy, PharmD, 2000-2002
Senior Manager, Gilead Sciences
Sherene Min, MD, 2000-2003
Clinical Assistant Professor of Medicine, UNC-Chapel Hill
Naumann Chaudry, PharmD, 1999-2001
Director, Medical Affairs, Pfizer
Mary Kennedy, PharmD, 1999-2001
Associate Director, Kosair Charities Pediatric Clinical Research Unit at University of Louisville, KY
Karl Gotzkowsky, PharmD, 1998-2000
Director, Product Development, United Therapeutics Corp., RTP, NC
Jodi Weidler, PharmD, 1997-1999
Senior Director, Clinical Research, Monogram Biosciences