Dr. Shirley M. Tsunoda: Transplantation

Research Summary: Transplantation & Drug Metabolism

Dr. Tsunoda’s research focuses on factors influencing the variability and activity of intestinal and hepatic metabolism of drugs and the pharmacokinetics/metabolism and clinical use of immunosuppressive agents. Previous work has included using probe compounds such as midazolam and cyclosporine to predict activity of CYP3A4, the major drug metabolizing enzyme in the intestine and liver and the effect of red wine on cyclosporine pharmacokinetics. She is also interested in studying the increasingly complex interplay of the metabolic enzymes and transporter proteins in the intestine and how they contribute to the overall bioavailability of immunosuppressive drugs.

Dr. Tsunoda has several ongoing research projects in transplant patients. These include: 1) investigating the antifibrotic activity of the immunosuppressive agent sirolimus in post-transplant hepatitis C; 2)
understanding factors contributing to successful treatment of post-transplant hepatitis C; 3)
investigating the outcomes of co-infected hepatitis B and HIV patients; and 4) investigating the clinical utility of an immune cell function assay as a biomarker in liver transplantation. Dr. Tsunoda maintains a clinical practice in the liver transplant clinic at UCSD.

Academic Achievements

Education: B.S. in Psychobiology (1987), UCLA; Pharm.D. (1992) UCSF; Residency in Pharmacy Practice (1993) UCSF; Post-doctoral Fellowship in Pharmacokinetics/Drug Metabolism (1995) UCSF.

Awards and Honors: UCSF Resident Research Project Award (1993); American Association of Colleges of Pharmacy New Investigator Award (1996); National Center for Leadership in Academic Medicine, UCSD (2007).

Leadership Experience: Alternate Delegate, American Association of Colleges of Pharmacy (1996-1999); Vice-Chair, Gastroenterology Endocrine and Metabolism Section, American Society of Clinical Pharmacology and Therapeutics (2009 – present).

Teaching

• Pharmacy: Therapeutics (SPPS 212A, SPPS 212B).
• Pharmacy Practice (SPPS 203).

Key Contributions to Pharmaceutical Sciences

• Differentiation of intestinal and hepatic CYP3A4 activity using midazolam as an in vivo probe.
• Investigation of factors contributing to the variability of CYP3A4 enzyme activity
• Clinical research in liver transplant patients
• Development of clinical pharmacist practice models in transplantation in the inpatient and ambulatory care setting

Selected Recent Publications

Tsunoda et al. (1999). Differentiation of intestinal and hepatic cytochrome P450 3A activity with use of midazolam as an in vivo probe: effect of ketoconazole. Clin Pharmacol Ther 66:461-471.

Tsunoda et al. (2001). Red wine decreases cyclosporine bioavailability. Clin Pharmacol Ther
70:462-467.

Tsunoda et al. (2008). Telbivudine for the treatment of hepatitis B disease. Future Virology 3:517-527.

Ma JD et al. (2010). Evaluation of in vivo p- glycoprotein phenotyping probes: a need for validation. Clin Pharmacokinet, 49:223-37.

Potential Collaborative Programs with the Pharmaceutical Industry

• Phase I investigations of new compounds that are CYP3A and/or p-glycoprotein substrates, particularly those used in transplantation.
• Phase I-III investigations of mTOR inhibitor compounds
• Pharmacokinetic and drug metabolism studies in liver disease and liver transplantation