HEMATOLOGIC MALIGNANCIES PROGRAM (Project-265) ABSTRACT Overview and Goals: Hematologic malignancies represent some of the most aggressive forms of cancer, and in many cases, current therapeutic options are very limited. Thus, the goal of the new Hematologic Malignancies (HEME) Program, which was formally established in early 2015, is to define key biological features of leukemia and related blood cancers and translate these into improved therapeutics. HEME was formed in 2015 based on the vision of the UCCC leadership with concurrence of our EAB and leverages the enormous growth in the hematologic malignancies community at AMC over the last 5 years. The major scientific strengths in HEME focus on the epigenetic regulation of cellular processes, key molecular events occurring as normal cells transition to malignant states, metabolic processes that define tumor-specific properties, and characterizing malignant stem cells. Research Highlight: Recently members discovered that germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia opening up novel avenues for prevention and assessment of cancer predisposition risk in such patients (Nat Genet, 20151). Program Activities: To accomplish this goal, HEME co-leaders employ resources provided by the CCSG to orchestrate intra- and inter-programmatic collaborations through organization of annual retreats and periodic technology forums, and routine chaperoning of transdisciplinary collaborations. Program members utilize Shared Resources (SR) for preclinical mouse models and employ patient-derived specimens and tumor models as a means to evaluate candidate therapies. In addition, work across the consortium with CSU/FACC on spontaneous disease models in companion animals complements an extensive adult and pediatric human clinical trials portfolio at that seeks to advance multiple targeted therapies across all ages. Members: The HEME program is comprised of 24 Full and 11 Associate members with 65 grants and $1.4M NCI and $1.3M other peer-reviewed cancer research grant funding in 2015. The group of multidisciplinary investigators includes the entire spectrum of pediatric and adult blood cancer research groups across the UCCC consortium. 86% of members (30) are located in 10 clinical and basic science departments at UCD and CSU; and the remainder are at non-consortium institutions. From program inception (7/2014) the group produced 77 cancer-focused publications, of which 32% were inter- and 13% intra-programmatic. Future Directions: We expect the HEME program to expand substantially. Ongoing recruitment efforts include clinical research leadership roles in immunotherapy, pediatric BMT, myeloma, and expertise in adolescent young adult (AYA) populations. In addition, growth in immunology, pharmacology and molecular biology is expected to further strengthen our basic science efforts. For this dynamic program, we will focus on supporting interdisciplinary and translational studies, collaborative projects, training and mentoring of junior investigators, and the development of key resources required for laboratory and clinical research.
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