PROJECT-005: TRANSLATIONAL THERAPEUTICS PROGRAM (TT) PROJECT SUMMARY / ABSTRACT The Translational Therapeutics Program at The Ohio State University Comprehensive Cancer Center (OSUCCC), led by David Carbone, MD, PhD and Denis Guttridge, PhD, unites an outstanding team of 55 basic, translational and/or clinical researchers from 17 departments within the Colleges of Business, Medicine, Engineering, Pharmacy, and Veterinary Medicine at Ohio State University. This Program is a continuation of the 15 year-old Experimental Therapeutics (ET) Program that included both liquid and solid tumors. However, as the result of a strategic effort to grow the solid tumor presence in the OSUCCC, we successfully recruited an additional 38 solid tumor physicians, basic scientists, and physician-scientists during this last funding cycle, 16 of who came into the ET Program. We also transitioned to new leadership in the departments of radiation oncology and pathology, as well as in the divisions of medical oncology, surgical oncology and gynecologic oncology, each with expertise in translational medicine and each a member of this Program. With more emphasis on translation and less emphasis on experimental pharmacology, we renamed the ET Program ?Translational Therapeutics (TT)?. Under the leadership of Drs. Carbone and Guttridge the TT Program has seen significant progress during the last cycle, producing 874 peer-reviewed publications among which 9% are in high impact (>10) journals, 28% from intra-programmatic collaborations, 43% from inter-programmatic collaborations; 59% are multi-institutional and 86% are collaborative publications. TT Program members have collaborated on programmatic grant submissions and have been awarded 2 NCI P01s, a U01, a U54 SPORE, and a U10 programmatic grant focused on solid tumor biology, as well as two T32 training grants. As a consequence of these and other collaborative efforts, the TT Program has $8.8M in current annual direct costs from peer-reviewed grants of which $7.3M (83%) is from the NCI. The TT Program is well-integrated with the clinical teams via participation in the multidisciplinary Disease Specific Research Groups. As such, there were 5,253 accruals to interventional clinical trials during the last funding cycle of which 4,357 (83%) were therapeutic; 2043 (47%) of the latter resulted from investigator-initiated clinical trials. The overall goal of the TT Program is to pursue solid tumor biology in order to develop and translate promising preclinical studies into innovative clinical trials for the successful prevention, diagnosis and treatment of solid tumors. This goal will be achieved by performing the following specific aims: 1) Identifying alterations in solid tumor signaling pathways to develop targeted therapeutics; 2) Identifying and therapeutically targeting tumor-host interactions; and 3) Improving upon or developing new approaches for determining prognosis, selecting appropriate therapy and evaluating the response to treatment. Future directions include continued strategic recruitments and heavy leveraging of the OSUCCC's Drug Development Institute (DDI) to move a number of our exciting compounds in the TT Program into the clinic for a variety of solid tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA016058-42
Application #
9390877
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
Project End
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
42
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Horowitz, Neil S; Larry Maxwell, G; Miller, Austin et al. (2018) Predictive modeling for determination of microscopic residual disease at primary cytoreduction: An NRG Oncology/Gynecologic Oncology Group 182 Study. Gynecol Oncol 148:49-55
Rahnemai-Azar, Amir A; Cloyd, Jordan M; Weber, Sharon M et al. (2018) Update on Liver Failure Following Hepatic Resection: Strategies for Prediction and Avoidance of Post-operative Liver Insufficiency. J Clin Transl Hepatol 6:97-104
Rebbeck, Timothy R (see original citation for additional authors) (2018) Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. Hum Mutat 39:593-620
Kodigepalli, Karthik M; Bonifati, Serena; Tirumuru, Nagaraja et al. (2018) SAMHD1 modulates in vitro proliferation of acute myeloid leukemia-derived THP-1 cells through the PI3K-Akt-p27 axis. Cell Cycle 17:1124-1137
Zhang, Tianyu; Xu, Jielin; Deng, Siyuan et al. (2018) Core signaling pathways in ovarian cancer stem cell revealed by integrative analysis of multi-marker genomics data. PLoS One 13:e0196351
Yang, Zhifen; Zhang, Jing; Jiang, Dadi et al. (2018) A Human Genome-Wide RNAi Screen Reveals Diverse Modulators that Mediate IRE1?-XBP1 Activation. Mol Cancer Res 16:745-753
LaPak, Kyle M; Vroom, Dennis C; Garg, Ayush A et al. (2018) Melanoma-associated mutants within the serine-rich domain of PAK5 direct kinase activity to mitogenic pathways. Oncotarget 9:25386-25401
Byrd, John C; Smith, Stephen; Wagner-Johnston, Nina et al. (2018) First-in-human phase 1 study of the BTK inhibitor GDC-0853 in relapsed or refractory B-cell NHL and CLL. Oncotarget 9:13023-13035
Kaffenberger, Benjamin H; Hinton, Alice; Krishna, Somashekar G (2018) The impact of underlying disease state on outcomes in patients with pyoderma gangrenosum: A national survey. J Am Acad Dermatol 79:659-663.e2
Chen, Shuliang; Bonifati, Serena; Qin, Zhihua et al. (2018) SAMHD1 suppresses innate immune responses to viral infections and inflammatory stimuli by inhibiting the NF-?B and interferon pathways. Proc Natl Acad Sci U S A 115:E3798-E3807

Showing the most recent 10 out of 2602 publications