Cheryl L. Zimmerman

Cheryl L. Zimmerman, Ph.D. Professor of Pharmaceutics Director of Graduate Studies Morse-Alumni Distinguished Teaching Professor   of Pharmaceutics Office: 9-149B Weaver-Densford Hall Telephone Number: 612-624-4611 FAX Number: 612-626-2125 E-mail Address: zimme005@umn.edu

Education:

B.S. in Pharmacy, 1976
University of Wisconsin

Ph.D. in Pharmaceutics, 1983
University of Washington

Research Interests:

The problem of optimal delivery of drugs is of significant clinical concern. From a physiological standpoint, a drug molecule has several significant barriers to traverse prior to reaching the general circulation: it must be absorbed from the site of administration, and it must avoid metabolism within cells and tissues. In order to develop appropriate strategies for the improvement of the bioavailability of a given compound, Dr. Zimmerman's research group has developed a wide range of in situ and in vivo techniques to study the absorption and metabolism of drugs in the intestine and liver.  Her long-standing interest in the oral delivery of prodrugs and the influence of enzymatic and diffusional barriers in the intestine is currently focused on the delivery of peptide prodrugs.

In situ and in vivo techniques are also being used in the areas of lung cancer chemoprevention. Despite persuasive scientific evidence and significant education regarding the use of tobacco, lung cancer continues to be a major source of mortality and morbidity. The route of exposure to a carcinogenic agent has a significant impact on its access to specific drug-metabolizing enzymes, some of which can activate it and others which deactivate it.  Understanding and modulating the mechanisms of tobacco-induced lung carcinogenesis would have a major impact on the health of the nation as well as on the overall costs of health care.  NNK is a tobacco-specific nitrosamine formed from nicotine during tobacco curing and smoking. NNK is remarkably organ-specific, in that it causes lung carcinogenesis irrespective of the route by which it is administered.  The reason for this organ-specific tumorigenesis has not been fully elucidated, but the tissue-specific retention of a carcinogenic NNK metabolite in rat lung was discovered in the Zimmerman lab.  The organ specificity of NNK carcinogenesis and the finding of stereoselective retention of its major tumorigenic metabolite form the basis of continued investigations in both the isolated perfused rat lung and in cell culture systems.  These preclinical models in Dr. Zimmerman's lab allow the design of pharmacokinetically appropriate strategies for chemoprevention.

Dr. Zimmerman’s group has also undertaken work to understand the role of disease on the drug-metabolizing enzymes, specifically the influence of sickle cell anemia on response to opioid analgesics. Patients with sickle cell anemia require high doses of opioid analgesics to treat the pain caused by vasoocclusive episodes, and many patients do not experience adequate pain relief. Studies in transgenic mice (carrying the gene for the human sickle hemoglobin) suggest that the disease itself may influence the pharmacokinetics and pharmacodynamics of opioid analgesics. It is hoped that these studies will lead to improved pain management in a clearly underserved population: the sufferers of sickle cell anemia.

Selected Publications:

Swati Nagar, Rory P. Remmel, Robert P. Hebbel, and Cheryl L. Zimmerman. Metabolism of opioids is altered in liver microsomes of sickle cell transgenic mice. Drug Metabolism and Disposition 32: 98-104 (2004).

S.S. Hecht, S.E. Murphy, S.G. Carmella, C.L. Zimmerman, L. Losey, I. Kramarczuk, M.R. Roe, S.S. Puumala, Y.S. Li, C. Le, J. Jensen, and D.K. Matsukami.  Effects of reduced cigarette smoking on the uptake of a tobacco-specific lung carcinogen. Journal of the National Cancer Institute 96(2): 107-15 (2004).

Cheryl L. Zimmerman, Zheng Wu, Pramod Upadhyaya, and Stephen S. Hecht. Stereoselective metabolism and tissue retention in rats of the individual enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), metabolites of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Carcinogenesis 25(7): 1237-1242 (2004).

Heng Song, Rachel Johns, George W. Griesgraber, Carston R. Wagner, and Cheryl L. Zimmerman. Disposition and oral bioavailability in rats of an antiviral and antitumor amino acid phosphoramidate prodrug of AZT-monophosphate. Pharmaceutical Research 20: 448-451 (2003).

Heng Song, George W. Griesgraber, Carston R. Wagner, and Cheryl L. Zimmerman. Pharmacokinetics of amino acid phosphoramidate monoesters of AZT in rats. Antimicrobial Agents and Chemotherapy 46: 1357-1363 (2002).

Pramod Upadhyaya, Cheryl L. Zimmerman, and Stephen S. Hecht. Metabolism and pharmacokinetics of N'-nitrosonornicotine in the Patas monkey. Drug Metabolism and Disposition 30: 1115-1122 (2002).