GASTROINTESTINAL CANCER GENETICS RESEARCH PROGRAM PROJECT SUMMARY/ABSTRACT The Gastrointestinal Cancer Genetics (GICG) Research Program is a basic discovery program with a strong translational focus. The overarching goals of the GICG program are to discover genetic and epigenetic causes of GI cancers and to translate these discoveries into development of novel therapeutic approaches and biomarkers for early detection, prevention, diagnosis, prognosis and prediction of drug responses for GI cancers. The program is organized around 3 scientific aims: (1) Discover and clinically translate genetic alterations in GI cancers; (2) Discover and clinically translate epigenetic changes in GI cancers; and (3) Develop novel methods and models to facilitate basic and translational GI cancer research.
The aims reflect the programs work to continue to: i) make groundbreaking discoveries in the genetic and epigenetic causes of GI cancers, and ii) achieve major clinical impact by translating these discoveries into new approaches for cancer detection, prevention, and treatment resulting in working groups and initiatives that coalesces program members with other cancer center investigators through interprogrammatic collaborations that result in preclinical and clinical research efforts, grants, and trial protocols. Extensive use of an array of shared resources, in particular, Genomics, Biostatistics, and Tissue Resources facilitate all aspects of member discoveries. Under the leadership of Sanford Markowitz (Co-Leader) and Zhenghe (John) Wang (Co-Leader) the GICG Program includes 18 full members and 3 associate members. Members represent 11 departments, and 83% of members are funded by 64 projects that give rise to a total of $5.5M in research grant funding (annual direct costs), of which $5.1M is peer-reviewed and $3.8M is NCI-funded. Between 2012 and 2016, GICG program members published 534 publications. Cancer and program related publications included 28% inter- programmatic, 18% intra-programmatic, 8% inter- and intra-programmatic and 8% that involved collaboration with another Cancer Center. This highly effective program has made major practice-changing contributions benefiting cancer patients. Examples include: i) an ongoing investigator-initiated (and Stand Up To Cancer [SU2C] supported) clinical trial of a novel targeted therapy for PI3KCA mutant CRCs; ii) an ongoing investigator-initiated clinical trial for biomarker driven detection of Barret?s esophagus; iii) FDA approval and commercial adoption of stool DNA screening for CRC based on detecting methylated DNA, an approach pioneered by GICG investigators and continued in an ongoing investigator-initiated clinical trial; iv) validation in two iconic epidemiology cohorts ? the Nurses? Health Study and the Health Professionals Follow-Up Study ? of the discovery of a predictive biomarker of sensitivity or resistance to colon cancer chemoprevention by aspirin; and v) adoption by the NCI NEXT program of clinical development of a small molecule inhibitor of 15-PGDH invented by GICG investigators.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee I - Transistion to Independence (NCI)
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Case Western Reserve University
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Li, Jiayang; Gresham, Kenneth S; Mamidi, Ranganath et al. (2018) Sarcomere-based genetic enhancement of systolic cardiac function in a murine model of dilated cardiomyopathy. Int J Cardiol 273:168-176
Enane, Francis O; Saunthararajah, Yogen; Korc, Murray (2018) Differentiation therapy and the mechanisms that terminate cancer cell proliferation without harming normal cells. Cell Death Dis 9:912
Lennon, Donald; Solchaga, Luis A; Somoza, Rodrigo A et al. (2018) Human and Rat Bone Marrow-Derived Mesenchymal Stem Cells Differ in Their Response to Fibroblast Growth Factor and Platelet-Derived Growth Factor. Tissue Eng Part A 24:1831-1843
Evans, Daniel R; Venkitachalam, Srividya; Revoredo, Leslie et al. (2018) Evidence for GALNT12 as a moderate penetrance gene for colorectal cancer. Hum Mutat 39:1092-1101
Augestad, Knut M; Keller, Deborah S; Bakaki, Paul M et al. (2018) The impact of rectal cancer tumor height on recurrence rates and metastatic location: A competing risk analysis of a national database. Cancer Epidemiol 53:56-64
Chen, Lechuang; Feng, Zhimin; Yue, Hong et al. (2018) Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA. Nat Commun 9:4585
Patel, Rutulkumar; Zhang, Luchang; Desai, Amar et al. (2018) Mlh1 deficiency increases the risk of hematopoietic malignancy after simulated space radiation exposure. Leukemia :
Lager, Angela M; Corradin, Olivia G; Cregg, Jared M et al. (2018) Rapid functional genetics of the oligodendrocyte lineage using pluripotent stem cells. Nat Commun 9:3708
Patel, Rutulkumar; Qing, Yulan; Kennedy, Lucy et al. (2018) MMR Deficiency Does Not Sensitize or Compromise the Function of Hematopoietic Stem Cells to Low and High LET Radiation. Stem Cells Transl Med 7:513-520
Desai, Amar; Zhang, Yongyou; Park, Youngsoo et al. (2018) A second-generation 15-PGDH inhibitor promotes bone marrow transplant recovery independently of age, transplant dose and granulocyte colony-stimulating factor support. Haematologica 103:1054-1064

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