Coronavirus Pandemic

Basic & Translational Research

John R. Crawford, MD, MS is the Director of the Neuro-Oncology Program. He is a member of the Pacific Pediatric Neuro-oncology Consortium (PNOC) and is the RCHSD/UCSD site principal investigator for PNOC 002: Safety, Phase 0, and Pilot Efficacy Study of vemurafenib, an oral inhibitor of BRAFV600E, in Children with Recurrent/Refractory BRAFV600E-mutant gliomas. He is also the RCHSD/UCSD PI for St. Jude SJYC07 Risk-Adapted Therapy for Children Less than 3 Years of Age with Embryonal Brain Tumors, High-Grade Glioma, Choroid Plexus Carcinoma or Ependymoma.

Jenny M. Kim, MD is the Director of the RCHSD Comprehensive Sickle Cell/Hemoglobinopathy program. She was awarded a UCSD Health Sciences Clinical and Translational Research Institute (CTRI) innovative technology pilot project for 2011-12 for her project "Biomarkers of Sickle Cell Disease". This project is a collaboration with Don Durden, MD (UCSD), Joel Linden, PhD (La Jolla Institute for Allergy and Immunology), Kelly Frazer, PhD (UCSD), and Jennifer Yu, MD, Pediatric Hematology/Oncology fellow and Courtney Thornburg, MD (UCSD)examining biomarkers of inflammation associated with vaso-occlusive pain in children with sickle cell disease in the hopes of finding new therapies to target these markers and improve the quality of life for people with sickle cell disease. She is a study committee member for Children’s Oncology Group Protocol ACNS0334 for the treatment of supratentorial PNET and medulloblastoma, and was the RCHSD principal investigator for the Norvartis EXJADE Expanded Access study.

William D. Roberts, MD is a founding member of the Neuroblastoma & Medulloblastoma Translational Research Consortium (NMTRC). He is a study committee member and the RCHSD/UC San Diego principal investigator for the NMTRC clinical trials, including the following: NMTRC008: A Feasibility Trial using Molecular-Guided Therapy for the Treatment of Patients with Relapsed and Refractory Childhood Cancer, NMTRC003: A Phase II Preventative Trial of DFMO as a Single Agent in Patients with High Risk Neuroblastoma in Remission. NMTRC005: A Randomized, Phase I/II trial of Irinotecan and Temozolomide compared to Irinotecan and Temozolomide in Combination with TPI 287 in Patients with Primary Refractory or Early Relapsed Neuroblastoma, and NMTRC004: A Phase I/II Trial of TPI 287 in Patients with Refractory or Recurrent Neuroblastoma and Medulloblastoma. He is a co-PI of a study of the molecular basis of metastasis in the Ewing Sarcoma Family of Tumors with Dr. Jing Yang, which was awarded a 2-year Hyundai Hope on Wheels grant in 2012. In conjunction with Dr. Giovanni Paternostro at the Sanford-Burnham Institute, he is the co-PI of a translational study to assess the optimum microenvironment for measuring drug sensitivity of acute leukemia cells. Along with Drs. Paula Arisitzabal, and Raul Ribeiro, he has developed a joint RCHSD/UCSD/St. Jude Children’s Research Hospital pediatric oncology international outreach program in Tijuana, Mexico, and is involved in the development of a similar program in La Paz, Mexico.

Deborah E. Schiff, MD conducts clinical research related to palliative care in her role as the Medical Director of the Hematology/Oncology Palliative Care Program. She is the Physician Coordinator of the RCHSD/UCSD/St. Jude Children’s Research Hospital Alliance. She is the RCHSD/UCSD principal investigator for the following St. Jude studies: ALLR18: A Phase II Study of Therapy for Pediatric Relapsed or Refractory Precursor B-cell Acute Lymphoblastic Leukemia and Lymphoma, AML08: A Phase III Randomized Trial of Clofarabine Plus Cytarabine Versus Conventional Induction Therapy and a Phase II Study of Natural Killer Cell Transplantation in Patients with Newly Diagnosed Acute Myeloid Leukemia, MEL06: Phase II Study Incorporating Pegylated Interferon in the Treatment for Children with High-Risk Melanoma, and TBANK: A Protocol for Collecting, Banking, and Distributing Human Tissue Samples.

Courtney Thornburg, MD, MS is the Director of the Hemophilia/Bleeding Disorder program. She has held a leadership role in several multi-center studies of the role of hydroxyurea in the management of sickle cell disease. She was the first author on a publication in Pediatric Blood and Cancer describing medication and visit adherence, the first author on a publication in Blood describing clinical events, and a co-author on other related manuscripts, including the primary paper which was published in Lancet. She has also been involved in multi-center studies of stroke prevention, pain management, quality of life, and neurocognitive outcomes. She is the principal investigator for the RCHSD/HTC Universal Data Collection Study and the HTRS Registry for public health surveillance of individuals with bleeding disorders. She is participating in the Kids-DOTT trial to better determine the optimal duration of anticoagulation therapy in pediatric thrombosis patients.

Jing Yang, PhD conducts basic science research related to metastases in cancer and Twist mutations in metastatic cancers. She is involved in the study of the molecular basis of metastasis in the Ewing Sarcoma Family of Tumors with Dr. Roberts, and Dr. Sun Choo, a Pediatric Hematology/Oncology fellow. She was awarded a 2007 NIH Director’s New Innovator Award to develop a novel Epithelial-Mesenchymal Transition in Tumor Metastasis detection/selection system in mice to identify, image and isolate migrating carcinoma cells in primary tumors and to explore the signal pathways that promote carcinoma cells to migrate and disseminate into distant organs.

Janet Yoon, MD is the RCHSD/UCSD principal investigator for Phase II Study of everolimus for recurrent or progressive low-grade gliomas in children, conducted through the Pacific Pediatric Neuro-Oncology Consortium.

Alice Yu, MD, PhD is pursuing translational cancer research. She chairs a multi-national Phase III trial of anti-GD2 in high-risk neuroblastoma, which is a pivotal trial for future licensing of this antibody by the FDA. In addition, Dr. Yu directs a research laboratory, which includes Drs. Diccianni and Batova. Their research focuses on the role of immune effector cells in immunotherapy of cancer, the role of micro-RNA in leukemia, and novel therapy of cancer targeting molecular abnormalities associated with chromosome 9p21, which is frequently altered in many types of cancer.

Peter E Zage, M.D.,Ph.D.  Our research has identified a key role for the ubiquitin ligase UBE4B in the regulation of receptor trafficking in neuroblastoma tumor cells.  The UBE4B gene is located in the chromosome 1p36 region deleted in approximately one-third of neuroblastoma tumors, and UBE4B gene expression is strongly associated with neuroblastoma patient outcomes.  UBE4B expression and activity are correlated with receptor trafficking, responses to therapy, and neuroblastoma tumor differentiation, suggesting it may function as a novel tumor suppressor, prognostic marker, and therapeutic target.  Using effective preclinical models of pediatric solid tumors developed in our laboratory, we have also identified several promising novel targeted agents for therapy, and we have translated many of these therapies into early phase clinical trials for children with relapsed and refractory solid tumors.  We have identified a number of pathways required for neuroblastoma tumor cell survival after 13-cis-retinoic acid treatment, and these studies are likely to identify treatment combinations using readily available drugs that can also be rapidly tested in clinical trials, leading to improved treatments, reduced relapse rates, and improved survival for children with all forms of cancer.  Our continued research looks to build on these findings through a better understanding of UBE4B-mediated growth factor receptor trafficking and its link to responses and resistance to targeted therapies and through direct targeting of receptor trafficking as a unique approach to pediatric solid tumor therapy.