Magee-Womens Research Institute & Foundation

Drug-drug and drug-excipient interactions

Studying the metabolism, transport, and disposition of drugs and evaluating the interactions between co-formulated drugs (e.g. dapivirine and levonorgestrel, islatravir and levonorgestrel), between a drug (active pharmaceutical ingredient, API) and excipients (e.g. Q-griffithsin and carbopol), and between separately formulated but potentially co-administered pharmaceutical products (e.g. dapivirine intravaginal ring and miconazole vaginal capsule). These studies will help us develop and optimize formulations as well as inform product labeling.

Physiologically-based pharmacokinetics (PBPK) for the female reproductive tract

Understanding systemic and local drug distributions and physiology of the female reproductive tract for PBPK development. A panel of antiretroviral and contraceptive drugs or drug candidates that represent diverse physicochemical properties (including molecular weight, solubility, hydrophobicity, polar surface area, protein binding, permeability, metabolism and transport, etc.) are being evaluated. Drug release and normal physiological features of the female reproductive tract including human tissue volume and blood flow are being investigated. All the data is being utilized to develop/refine a PBPK model, which will in turn, be utilized to predict in vivo drug exposure in systemic and local compartments.

Drug delivery systems

Developing drug delivery systems and assessing such systems with respect to safety, functionality, and efficacy. I am part of the leadership team within the Rohan Pharmaceutics Laboratory that develops monthly vaginal films for HIV prevention and contraception. The distinguishing attributes of polymeric films, including portability, scalability, affordability, and discreetness, position them as an acceptable and empowering drug delivery option for women in low socioeconomic settings. Building upon our success for on-demand and weekly films, we recently developed monthly films for anti-infectives, contraceptives, and multipurpose prevention technologies. Our “bench to bedside” approach combines behavioral research, expansion of basic knowledge of the female reproductive tract, computational modeling, and formulation strategies.

• Zheng, R.; Valicherla, G. R.; Zhang, J.; Nuttall, J.; Silvera, P.; Marshall, L. J.; Empey, P. E.; Rohan, L. C. “Transport and permeation properties of dapivirine: understanding potential drug-drug interactions”, Pharmaceutics 2022, 14, 1948.
• Valicherla, G. R.; Graebing, P.; Zhang J.; Zheng, R.; Nuttall, J.; Silvera, P.; Rohan, L. C. “Investigating the contribution of drug-metabolizing enzymes in drug-drug interactions of dapivirine and miconazole”, Pharmaceutics 2021,13(12), 2193.
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  Zhang, J.; Tang, C.; Oberly, P. J.; Minnigh, M. B.; Achilles, S. L.; Poloyac, S.M. “A sensitive and robust UPLC–MS/MS method for quantitation of estrogens and progestogens in human serum”, Contraception 2019, 99, 244.
• Casey, A. K.; Moehlman, A. T.; Zhang, J.; Servage, K. A.; Kramer, H.; Orth, K. “Fic-mediated deAMPylation is not dependent on homodimerization and rescues toxic AMPylation in flies”, J. Biol. Chem. 2017, 292, 21193.
• Zhang, J.; Corbett, J. R.; Plymire, D. A.; Greenburg, B. M.; Patrie, S.M. “Proteoform analysis of lipocalin-type prostaglandin D-synthase from human cerebrospinal fluid by isoelectric focusing and superficially porous liquid chromatography with Fourier transform mass spectrometry”, Proteomics 2014, 14, 1223.
• Zhang, J.; Roth, M. J.; Chang, A. N., Plymire, D. A.; Corbett, J. R.; Greenburg, B. M.; Patrie, S. M. “Top-down mass spectrometry on tissue extracts and biofluids with isoelectric focusing and superficially porous silica liquid chromatography”, Anal. Chem. 2013, 85, 10377.
• Bajpai, R.; Chen, D. A.; Rada-Iglesias, A.; Zhang, J.; Xiong, Y.; Helms, J.; Chang, C. P.; Zhao, Y.; Swigut, T.; Wysocka, J. “CHD7cooperates with PBAF to control multipotent neural crest formation”, Nature 2010, 463, 958.
• Peng, J.; Valouev, A.; Swigut, T.; Zhang, J.; Zhao, Y.; Sidow, A.; Wysocka, J. “Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells”, Cell 2009,139, 1290.
• Lin, Y.; Lu, J.; Zhang, J.; Walter, W.; Dang, W.; Wan, J.; Tao, S. C.; Qian, J.; Zhao, Y.; Boeke, J. D.; Berger, S. L.; and Zhu, H. “Protein acetylation microarray reveals that NuA4 controls key metabolic target regulating gluconeogenesis”, Cell 2009, 136, 1073.
• Basu, A.; Rose, K. L.; Zhang, J.; Beavis, R. C.; Uberheide, B.; Garcia, B. A.; Chait, B.; Zhao, Y.; Hunt, D. F.; Segal, E.; Allis, C. D.; Hake, S. B. “Proteome-wide prediction of acetylation substrates”, Proc. Natl. Acad. Sci. U. S. A. 2009, 106 (33), 13785.
• Zhang, J.; Sprung, R.; Pei, J.; Tan, X.; Kim, S.; Zhu, H.; Liu, C. F.; Grishin, N. V.; Zhao, Y. “Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia Coli”, Mol. Cell. Proteomics 2009, 8, 215.
• Zhang, J.; Brodbelt, J. S. “Silver complexation and tandem mass spectrometry for differentiation of isomeric flavonoid diglycosides”, Anal. Chem. 2005, 77, 1761.
• Jang, H. Y.; Hughes, F. W.; Gong, H.; Zhang, J.; Brodbelt, J. S.; Krische, M. J. “Enantioselective reductive cyclization of 1,6-enynes via rhodium catalyzed asymmetric hydrogenation: C-C bond formation precedes hydrogen activation”, J. Am. Chem. Soc. 2005, 127, 6174.
• Keller, K. M.; Zhang, J.; Oehlers, L.; Brodbelt, J. S. “Influence of initial charge state on fragmentation patterns for non-covalent drug/DNA duplex complexes”, J. Mass Spectrom. 2005, 40, 1362.
• Zhang, J.; Brodbelt, J. S. “Gas-phase hydrogen/deuterium exchange and conformations of deprotonated flavonoids and gas-phase acidities of flavonoids”, J. Am. Chem. Soc. 2004, 126, 5906.
• Zhang, J.; Satterfield, M. B.; Brodbelt, J. S.; Britz, S. J.; Clevidence, B.; Novotny, J. A. “Structural characterization and detection of kale flavonoids by electrospray ionization mass spectrometry”, Anal. Chem. 2003, 75, 6401.
• For additional publications, please visit Pubmed.