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.