Dr. Synold 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 (CCC). 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 CNS 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 (CCC). City of Hope and California Cancer Consortium have been continuously funded to perform NCI/CTEP-sponsored Phase I and Phase II clinical trials for more than 20 years, and Dr. Synold’s group has designed and performed over one hundred 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 Drs. Jana Portnow and Behnam Badie. 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 CNS metastases.
In collaboration with Dr. Karen Aboody, 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 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 4-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.