Timothy Synold, Pharm.D.

Timothy Synold, Pharm.D., is a clinical and molecular pharmacologist who serves as director of the Analytical Pharmacology Laboratory. He is also the scientific leader of the City of Hope Phase I Clinical Trial team and director of Pharmacology for the NCI-supported California Cancer Consortium. Dr. Synold has over 25 years experience in chemistry and pharmacology, and he is an expert in the fields of pharmacokinetics and pharmacodynamics. His current research focus involves the role of the blood-brain-barrier in central nervous system penetration of drugs.

The Synold lab provides pharmacology and analytical chemistry expertise in a team science approach to the development of new treatments for cancer. The lab is actively involved in studying the pharmacokinetics and pharmacodynamics of novel anticancer agents under clinical investigation at City of Hope, as well as within the California Cancer Consortium. City of Hope and California Cancer Consortium have been continuously funded to perform National Cancer Institute/CTEP-sponsored phase I and phase II clinical trials for more than 20 years, and Dr. Synold’s group has designed and performed over 100 preclinical and clinical investigations in support of early drug development. On a national level, Dr. Synold’s group participates in the clinical development of new cancer drugs through his role as director of Pharmacokinetics for the Early Therapeutic Committee of the Southwest Oncology Group, and as a founding member of the NCI’s Organ Dysfunction Group.

Dr. Synold has also helped to create the City of Hope Intracranial Microdialysis Program, along with Jana Portnow, M.D., and Behnam Badie, M.D. The program is the largest of its kind in U.S. and continues to grow with more than 50 patients enrolled on six completed studies and two ongoing clinical trials. Intracranial microdialysis is a powerful research tool that allows one to answer important questions about a drug’s ability to penetrate the blood-brain barrier. As experts in the clinical research application of this new platform, Dr. Synold and his colleagues have attracted several new studies of agents targeting primary brain tumors and central nervous system metastases.

In collaboration with Karen Aboody, M.D., the Synold lab is also investigating the ability of neural stem cells to deliver a pro-drug activating transgene directly to the site of brain tumors in vivo. This collaboration builds on our clinical and preclinical experience with intracranial microdialysis to assess the neuropharmacokinetics and neuropharmacodynamics of drugs. As the project leader of Team 4 (Pharmacology) for the recently completed California Institute for Regenerative Medicine (CIRM) funded $18 million Disease Team Concept Proposal, Dr. Synold has developed an intracranial microdialysis nude rat model for the selection of the optimal enzyme variant and route of neural stem cell administration for the first-in-human clinical trial. Studies performed in the laboratory have been critical for successful completion of the milestones, which led to the approval of an investigational new drug (IND) for a first-in-human clinical trial.

In addition to the CIRM-funded project described above, Drs. Synold and Aboody are developing these genetically modified stem cells to be used for the treatment of neuroblastoma, a rare but deadly tumor in children. As in the CIRM-funded project, the overall goal of this four-year project is to perform the necessary IND-enabling studies that will allow us to deliver the stem cells directly into patients by the end of the funding period. Dr. Synold’s role is to design and perform experiments aimed at determining the optimal timing and doses of both stem cells and pro-drug in order to maximize the therapeutic efficacy of this novel approach.

Synold TW, Dussault I, Forman BM. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med. 2001 May;7(5):584-90. PubMed PMID:11329060.

Gu L, Tsark WM, Brown DA, Blanchard S, Synold TW, Kane SE. A new model for studying tissue-specific mdr1a gene expression in vivo by live imaging. Proc Natl Acad Sci USA. 2009 Mar 31;106(13):5394-9. PubMed PMID: 19282474.

Synold TW, Takimoto CH, Doroshow JH, Gandara D, Mani S, Remick SC, Mulkerin DL, Hamilton A, Sharma S, Raman than RK, Lenz HJ, Graham M, Longmate J, Kaufman BM, Ivy P; National Cancer Institute Organ Dysfunction Working Group. Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study. Clin Cancer Res. 2007 Jun 15;13(12):3660-6. PubMed PMID: 17575231.

Shibata SI, Chung V, Synold TW, Longmate JA, Suttle AB, Ottesen LH, Lenz HJ, Kummar S, Harvey RD, Hamilton AL, O'Neil BH, Sarantopoulos J, LoRusso P, Rudek MA, Dowlati A, Mulkerin DL, Belani CP, Gandhi L, Lau SC, Ivy SP, Newman EM. Phase I study of pazopanib in patients with advanced solid tumors and hepatic dysfunction: a National Cancer Institute Organ Dysfunction Working Group study. Clin Cancer Res. 2013 Jul 1;19(13):3631-9. PubMed PMID: 23653147.

Hurria A, Blanchard MS, Synold TW, Mortimer J, Chung CT, Luu T, Katheria V, Rotter AJ, Wong C, Choi A, Feng T, Ramani R, Doan CM, Brown J, Somlo G. Age-related changes in nanoparticle albumin-bound paclitaxel pharmacokinetics and pharmacodynamics: influence of chronological versus functional age. Oncologist. 2015 Jan;20(1):37-44. PubMed PMID: 25492923.

Portnow J, Badie B, Chen M, Liu A, Blanchard S, Synold TW. The neuropharmacokinetics of temozolomide in patients with resectable brain tumors: potential implications for the current approach to chemoradiation. Clin Cancer Res. 2009 Nov 15;15(22):7092-8. PubMed PMID: 19861433.

Portnow J, Badie B, Markel S, Liu A, D'Apuzzo M, Frankel P, Jandial R, Synold  TW. A neuropharmacokinetic assessment of bafetinib, a second generation dual BCR-Abl/Lyn tyrosine kinase inhibitor, in patients with recurrent high-grade gliomas. Eur J Cancer. 2013 May;49(7):1634-40. PubMed PMID: 23380277.

Portnow J, Badie B, Liu X, Frankel P, Mi S, Chen M, Synold TW. A pilot microdialysis study in brain tumor patients to assess changes in intracerebral cytokine levels after craniotomy and in response to treatment with a targeted anti-cancer agent. J Neurooncol. 2014 May;118(1):169-77. PubMed PMID: 24634191.

Portnow J, Synold TW, Badie B, Tirughana R, Lacey SF, D'Apuzzo M, Metz MZ, Najbauer J, Bedell V, Vo T, Gutova M, Frankel P, Chen MY, Aboody KS. Neural stem cell-based anti-cancer gene therapy: a first-in-human study in recurrent high grade glioma patients. Clin Cancer Res. 2016 Dec 15 [Epub ahead of print]. PubMed PMID: 27979915.

Portnow J, Badie B, Chen M, Liu A, Blanchard S, Synold TW. The neuropharmacokinetics of temozolomide in patients with resectable brain tumors: potential implications for the current approach to chemoradiation. Clin Cancer Res. 2009 Nov 15;15(22):7092-8. PubMed PMID: 19861433.

Portnow J, Badie B, Markel S, Liu A, D'Apuzzo M, Frankel P, Jandial R, Synold  TW. A neuropharmacokinetic assessment of bafetinib, a second generation dual BCR-Abl/Lyn tyrosine kinase inhibitor, in patients with recurrent high-grade gliomas. Eur J Cancer. 2013 May;49(7):1634-40. PubMed PMID: 23380277.

Portnow J, Badie B, Liu X, Frankel P, Mi S, Chen M, Synold TW. A pilot microdialysis study in brain tumor patients to assess changes in intracerebral cytokine levels after craniotomy and in response to treatment with a targeted anti-cancer agent. J Neurooncol. 2014 May;118(1):169-77. PubMed PMID: 24634191.

Portnow J, Synold TW, Badie B, Tirughana R, Lacey SF, D'Apuzzo M, Metz MZ, Najbauer J, Bedell V, Vo T, Gutova M, Frankel P, Chen MY, Aboody KS. Neural stem cell-based anti-cancer gene therapy: a first-in-human study in recurrent high grade glioma patients. Clin Cancer Res. 2016 Dec 15 [Epub ahead of print]. PubMed PMID: 27979915.

Complete List of publications in My Bibliography