This is a proposal to establish a Center of Biomedical Research Excellence (COBRE) focusing on Cancer Biology with emphasis on the identification, functional characterization, and targeting of tumor specific markers and antigens. Our center will use cell and molecular biology, immunology, nanoparticle technology, and animal models to examine the development, detection, and treatment of human cancer. Five research projects are included. The goals of Project 1 (Meena Jaggi, PhD) are to understand the effects of protein kinase Dl on (3- catenin-mediated signaling and to determine if PKDl expression influences tumor progression through this pathway. For Project 2 (Kristi Egland, PhD) a large number of membrane and secreted proteins that are expressed at elevated levels in prostate cancer cells were identified. This information will be used to develop a new diagnostic test for prostate cancer that detects autoantibodies in patient serum. Project 3 (Satoshi Nagata, PhD) will develop a panel of monoclonal antibodies to surface antigens that are highly expressed in B cell malignancies. These antibodies will be tested for their potential use in immunotherapies. Project 4 (Subhash Chauhan, PhD) will develop novel methods of treatment and drug delivery for pancreatic cancer. The goal will be to combine radioimmunotherapy and nanoparticle technology for highly specific delivery of cytotoxic compounds. Project 5 (William Spanos, MD) will focus on the role of the immune response in tumor clearance following treatment of head and neck squamous cell carcinoma. A strong mentoring plan will take advantage of the experience of an outstanding group of senior faculty with active research programs. Mentors will provide guidance for research design, manuscript preparation, grant applications, and other crucial aspects of career development. An EAC consisting of five internationally recognized scientists with broad experience in basic, translational, and clinical research has been assembled. Research capabilities will be supported by core facilities in Molecular Pathology, Flow Cytometry, Tumor Biology, and Imaging. We v""""""""ll recruit 3 high quality junior investigators and 1 established investigator. We will train students and post-doctoral fellows, support a seminar series, and fund pilot research projects in the field of cancer research.

Public Health Relevance

There is currently no comprehensive cancer center in the state of South Dakota that encompasses clinical, basic and translational cancer research. With this COBRE there will be a sizable increase in the number of scientists in South Dakota engaged in cancer research. The result of COBRE funding will be a substantially improved and modernized research infrastructure, forming the foundation for cancer research in this region.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
1P20RR024219-01A2
Application #
7822091
Study Section
Special Emphasis Panel (ZRR1-RI-B (01))
Program Officer
Caldwell, Sheila
Project Start
2011-09-02
Project End
2016-06-30
Budget Start
2011-09-02
Budget End
2012-06-30
Support Year
1
Fiscal Year
2011
Total Cost
$2,251,826
Indirect Cost
Name
Sanford Research/Usd
Department
Type
DUNS #
050113252
City
Sioux Falls
State
SD
Country
United States
Zip Code
57104
Radichev, Ilian A; Maneva-Radicheva, Lilia V; Amatya, Christina et al. (2016) Loss of Peripheral Protection in Pancreatic Islets by Proteolysis-Driven Impairment of VTCN1 (B7-H4) Presentation Is Associated with the Development of Autoimmune Diabetes. J Immunol 196:1495-506
Coppock, Joseph D; Vermeer, Paola D; Vermeer, Daniel W et al. (2016) mTOR inhibition as an adjuvant therapy in a metastatic model of HPV+ HNSCC. Oncotarget 7:24228-41
Terrier, Benjamin; Nagata, Satoshi; Ise, Tomoko et al. (2014) CD21(-/low) marginal zone B cells highly express Fc receptor-like 5 protein and are killed by anti-Fc receptor-like 5 immunotoxins in hepatitis C virus-associated mixed cryoglobulinemia vasculitis. Arthritis Rheumatol 66:433-43
Maneva-Radicheva, Lilia; Amatya, Christina; Parker, Camille et al. (2014) Autoimmune diabetes is suppressed by treatment with recombinant human tissue Kallikrein-1. PLoS One 9:e107213
Evans, Rick L; Pottala, James V; Egland, Kristi A (2014) Classifying patients for breast cancer by detection of autoantibodies against a panel of conformation-carrying antigens. Cancer Prev Res (Phila) 7:545-55
Gara, Rishi Kumar; Sundram, Vasudha; Chauhan, Subhash C et al. (2013) Anti-cancer potential of a novel SERM ormeloxifene. Curr Med Chem 20:4177-84
Molavi, Ommoleila; Xiong, Xiao-Bing; Douglas, Donna et al. (2013) Anti-CD30 antibody conjugated liposomal doxorubicin with significantly improved therapeutic efficacy against anaplastic large cell lymphoma. Biomaterials 34:8718-8725
Khan, Sheema; Ansarullah; Kumar, Deepak et al. (2013) Targeting microRNAs in pancreatic cancer: microplayers in the big game. Cancer Res 73:6541-7
Coppock, Joseph D; Wieking, Bryant G; Molinolo, Alfredo A et al. (2013) Improved clearance during treatment of HPV-positive head and neck cancer through mTOR inhibition. Neoplasia 15:620-30
Yallapu, Murali M; Jaggi, Meena; Chauhan, Subhash C (2013) Curcumin nanomedicine: a road to cancer therapeutics. Curr Pharm Des 19:1994-2010

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