Cellular Mechanisms (CM) is a new research program in the Masonic Cancer Center (MCC) formed when the Cell Signaling and Tumor Microenvironment Programs merged into one highly integrated program to strengthen the science of cellular mechanisms of cancer and expand opportunities for translation of research discoveries into new therapeutic modalities. The Program?s goal is to identify biological mechanisms that drive cancer development, tumor progression, and metastasis, including therapy-resistant recurrence, and then develop novel targeted therapies. The 3 integrated Aims are 1) to identify oncogenic signaling pathways within and between diverse cells in tumors that can be targeted to limit tumor growth, invasion, and metastasis; 2) to define epigenetic events in tumor transcriptomes that enhance malignancy or resistance to therapy; 3) to determine how tumors cause protumorigenic changes in the associated stroma and how ?cancerized? stroma and tumor-reactive host cells impact tumor progression, invasion, migration, and metastasis. The Program is co-led by Drs. Carol Lange and James McCarthy and has 45 members, representing 19 departments and 8 schools or colleges. For the last budget year, CM members were supported by $4.8 million in direct costs from the National Cancer Institute; cancer-focused, sponsored funding from all sources totaled over $10.7 million (direct costs). Since 2013, CM members have published 1027 papers, 8% of which resulted from intraprogrammatic collaborations, 22% from interprogrammatic collaborations, and 82% from external collaborations; 89 were published in journals with an impact score of 10 or higher. Since 2013, 221 clinical trials across all clinical research categories have opened under this programmatic area and have accrued 1132 subjects. The MCC has provided substantial value to the program, including recruitment of 5 new faculty and funding of $1.08M in pilot projects that have led to over $5.5 million in externally funded grants. CM members use all 10 MCC Shared Resources. In addition, the MCC was instrumental in supporting the 2nd annual Regional Midwest Tumor Microenvironment Meeting in May of 2015, which hosted 132 attendees from 7 academic institutions. Members of this well-integrated interdisciplinary Program bring complimentary expertise to identifying how tumor and host cell interactions impact tumor progression, elucidating the complexities of metastatic and hormone-refractory disease, and determining how deregulation of signaling inputs to transcriptional control might be exploited to improve therapy. The study of targetable factors related to stroma remodeling and fibrosis is also a research strength. Novel therapies are being developed using antibodies, recombinant toxins, small molecules, and medicinal chemistry/fragment-based drug design to target signaling pathways and alter tumor metabolism. Program members have substantial interactions with the Immunology and Genetic Mechanisms Programs. The CM Program fulfills key components of the Cellular and Molecular Therapeutics and Biomarker Discovery (SPG1 and SPG4) MCC Strategic Scientific Priorities.

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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University of Minnesota Twin Cities
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Ma, Bin; Zarth, Adam T; Carlson, Erik S et al. (2018) Methyl DNA Phosphate Adduct Formation in Rats Treated Chronically with 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and Enantiomers of Its Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol. Chem Res Toxicol 31:48-57
Hatsukami, Dorothy K; Luo, Xianghua; Jensen, Joni A et al. (2018) Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Biomarkers of Smoke Exposure: A Randomized Clinical Trial. JAMA 320:880-891
Lee, Hak Rae; Leslie, Faith; Azarin, Samira M (2018) A facile in vitro platform to study cancer cell dormancy under hypoxic microenvironments using CoCl2. J Biol Eng 12:12
Yang, Libang; Herrera, Jeremy; Gilbertsen, Adam et al. (2018) IL-8 mediates idiopathic pulmonary fibrosis mesenchymal progenitor cell fibrogenicity. Am J Physiol Lung Cell Mol Physiol 314:L127-L136
Regan Anderson, Tarah M; Ma, Shihong; Perez Kerkvliet, Carlos et al. (2018) Taxol Induces Brk-dependent Prosurvival Phenotypes in TNBC Cells through an AhR/GR/HIF-driven Signaling Axis. Mol Cancer Res 16:1761-1772
Grzywacz, Bartosz; Moench, Laura; McKenna Jr, David et al. (2018) Natural Killer Cell Homing and Persistence in the Bone Marrow After Adoptive Immunotherapy Correlates With Better Leukemia Control. J Immunother :
Santiago, Victor; Lazaryan, Aleksandr; McClune, Brian et al. (2018) Quantification of marrow hematogones following autologous stem cell transplant in adult patients with plasma cell myeloma or diffuse large B-cell lymphoma and correlation with outcome. Leuk Lymphoma 59:958-966
Guo, Jingshu; Villalta, Peter W; Weight, Christopher J et al. (2018) Targeted and Untargeted Detection of DNA Adducts of Aromatic Amine Carcinogens in Human Bladder by Ultra-Performance Liquid Chromatography-High-Resolution Mass Spectrometry. Chem Res Toxicol :
Boatman, Jeffrey A; Vock, David M; Koopmeiners, Joseph S et al. (2018) Estimating causal effects from a randomized clinical trial when noncompliance is measured with error. Biostatistics 19:103-118
Rashidi, Armin; Shanley, Ryan; Yohe, Sophia L et al. (2018) Recipient single nucleotide polymorphisms in Paneth cell antimicrobial peptide genes and acute graft-versus-host disease: analysis of BMT CTN-0201 and -0901 samples. Br J Haematol 182:887-894

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