The Tumor Biology and Microenvironment (TBM) Program aims to eradicate cancer by identifying the cellular and molecular mechanisms that drive interactions between tumors and their microenvironments, and develop and test innovative diagnostic and treatment strategies. This highly integrated program includes 36 members from 16 WSU departments and $14,193,608 in grants, of which $5,908,215 is peer reviewed. The Program goals are addressed with three themes that encompass basic, preclinical, and clinical research. The first theme identifies and exploits the mechanisms that confer phenotypical plasticity and survival of tumor cells in tumor progression. Translational research is conducted to evaluate the potential clinical application of these molecular determinants as tumor markers and/or therapeutic targets. The second theme identifies and exploits the mechanisms that confer the unhealable wounding of tumor stroma. Our investigators identify and characterize factors in an extracellular proteolysis and signaling network that enable tumor cells to adapt to and subvert the microenvironment in the development of bone metastases. Key molecules in this network are evaluated to determine if they can be used to predict cancer progression and treatment outcomes. The third theme identifies and exploits the host immune response to tumor progression. Bispecific antibody-armed activated T-cells are tested in solid tumors and hematologic malignancies in the context of chemotherapy or high dose chemotherapy and stem cell transplantation. Anti-tumor DNA vaccines are developed and tested using mouse and domesticated cat models. Our investigators study immune modulators and inhibitors of adverse pro-inflammatory responses. Our members also develop novel vehicles to deliver immunotherapeutic agents. TBM Program members actively collaborate with members of the MI, MT, and PSDR Programs at KCI. Of the 612 manuscripts published from December 2010 to November 2014, 44% and 38% were intra- and inter-programmatic, respectively, and 27% were multi-institutional collaborations.

Public Health Relevance

In 2014, there were an estimated 1,665,540 new cancer cases diagnosed and 585,720 cancer deaths in the United States. Cancer remains the second most common cause of death in the US, accounting for nearly 1 of every 4 deaths (source: American Cancer Society). The Karmanos Cancer Institute is a unique, urban-based integrated center of research, patient care and education, dedicated to the prevention, early detection, treatment and eventual eradication of cancer. Key to achieving this mission is KCI's research effort which is conducted among four interdisciplinary Programs, organized to integrate basic, translational, and clinical research with population research-based cancer control activities.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA022453-36
Application #
9384720
Study Section
Subcommittee I - Transistion to Independence (NCI)
Program Officer
Ptak, Krzysztof
Project Start
1997-08-08
Project End
2020-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
36
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Wayne State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Munkanatta Godage, Dhanushka N P; VanHecke, Garrett C; Samarasinghe, Kusal T G et al. (2018) SMYD2 glutathionylation contributes to degradation of sarcomeric proteins. Nat Commun 9:4341
Han, Jing; Li, Yue; Liu, Xiuli et al. (2018) Metformin suppresses retinal angiogenesis and inflammation in vitro and in vivo. PLoS One 13:e0193031
Rathinam, Rajamani; Rosati, Rita; Jamesdaniel, Samson (2018) CRISPR/Cas9-mediated knockout of Lim-domain only four retards organ of Corti cell growth. J Cell Biochem 119:3545-3553
Kim, Seongho; Wong, Weng Kee (2018) Discussion on Optimal treatment allocations in space and time for on-line control of an emerging infectious disease. J R Stat Soc Ser C Appl Stat 67:778-779
Singh, Kshipra; Coburn, Lori A; Asim, Mohammad et al. (2018) Ornithine Decarboxylase in Macrophages Exacerbates Colitis and Promotes Colitis-Associated Colon Carcinogenesis by Impairing M1 Immune Responses. Cancer Res 78:4303-4315
McKnight, Brooke N; Kuda-Wedagedara, Akhila N W; Sevak, Kuntal K et al. (2018) Imaging EGFR and HER3 through 89Zr-labeled MEHD7945A (Duligotuzumab). Sci Rep 8:9043
An, Myunggi; Yu, Chunsong; Xi, Jingchao et al. (2018) Induction of necrotic cell death and activation of STING in the tumor microenvironment via cationic silica nanoparticles leading to enhanced antitumor immunity. Nanoscale 10:9311-9319
Neslund-Dudas, Christine M; McBride, Russell B; Kandegedara, Ashoka et al. (2018) Association between cadmium and androgen receptor protein expression differs in prostate tumors of African American and European American men. J Trace Elem Med Biol 48:233-238
Kraniak, Janice M; Chalasani, Anita; Wallace, Margaret R et al. (2018) Development of 3D culture models of plexiform neurofibroma and initial application for phenotypic characterization and drug screening. Exp Neurol 299:289-298
Negmeldin, Ahmed T; Knoff, Joseph R; Pflum, Mary Kay H (2018) The structural requirements of histone deacetylase inhibitors: C4-modified SAHA analogs display dual HDAC6/HDAC8 selectivity. Eur J Med Chem 143:1790-1806

Showing the most recent 10 out of 826 publications