Developmental Research

Director:
Eric Fearon, M.D., Ph.D.

Support for developmental research projects are a key SPORE element and are vital for fostering pioneering initiatives. As such, we will commit $140,000 annually to support three developmental research projects with budgets of approximately $45,000 each. The principal goal of the Developmental Research Program is to support innovative gastrointestinal cancer research with high translational impact, allowing investigators the ability to obtain key preliminary data for submission of an RO1 application or an equivalent proposal (e.g., project in future SPORE application). Previously funded developmental research projects that have strong success during the initial funding period, but that have not obtained extramural funding, will be permitted to compete with new applications, with a maximum of two years of support possible. However, the expectation is that funds will support most projects for 1 year, with upwards of 15 new projects supported during the initial 5-year period of the grant. Projects will be solicited from University of Michigan Comprehensive Cancer Center (UMCCC) investigators and other University of Michigan faculty by campus-wide announcements and a standing advertisement for the Program at the UMCCC website listing other developmental research opportunities. Applications will utilize an NIH PHS398 format, with a 5-page limit on the body of the application (e.g., excluding references, detailed protocol information, appendix materials). Dr. Eric Fearon will serve as Director of the Developmental Research Program, and the UMCCC Cancer Research Committee (CRC) will undertake initial review, evaluating each proposal's scientific merit, innovation, gastrointestinal cancer relevance, and potential for translational impact. Given the CRC's expertise with rapid review of more than 100 pilot research proposals in laboratory, clinical, and population-based research annually, the CRC is well acquainted with review of projects with limited preliminary data. After review by the CRC, the Senior Advisory Group of the GI SPORE will utilize assigned merit scores as a principal, but not sole, criterion in selection of proposals for support. Developmental research project investigators will take part in all GI SPORE activities, and Dr. Fearon will meet quarterly with project PIs to offer in-depth review and mentorship.


DEVELOPMENT RESEARCH PILOT PROJECT

 

Quantitation of Fatty Acids from Mucinophilic Bacteria in Human Serum

Principle Investigator:
Zora Djuric, Ph.D, Research Professor
Family Medicine, Medical School, Environmental Health Sciences

Co-Investigator(s):
Ananda Sen, Ph.D, Research Associate Professor
Department of Biostatistics and Department of Family Medicine

Eric Martens, Ph.D, Assistant Professor

11/1/2012 - 10/31/2013

The purpose of this project is to develop methods to profile fatty acids in mucinophilic bacteria by GC-MS, to identify and quantify the most prominent bacterial fatty acids in existing samples of human serum from a clinical dietary intervention trial, to quantify other markers of systemic endotoxin levels (LAL assay) and mediators of the response to lipopolysaccheride (LPS) such as LPS binding protein, sCD14, RELMβ, pro- and anti-inflammatory cytokines, and leptin and to use the data generated in grant applications that will investigate the effects of diet composition with and without weight loss on endotoxin exposures and colonic biomarkers of pro-inflammatory signaling relevant to the LPS/TLR4/RELMβ/NFκB pathway.

 

 

Notch Pathway Regulation of Gastric Tumorigenesis

Principle Investigator:
Linda Samuelson, Ph.D., Professor
Molecular & Integrative Physiology

11/1/2012 - 10/31/2013

Emerging studies suggest that Notch signaling is activated in gastric cancer, but the significance of this activation has not yet been established. The researcher's unpublished studies in genetic mouse models show that Notch regulates gastric stem cell proliferation and that constitutive Notch activation in stem cells induces hyperplasia and polyp formation. These studies suggest Notch activation may be important for promoting or sustaining gastric cancer.

 

 

Understanding host-microbial relationships during inflammation-related tumorigenesis

Project Investigator:
Grace Chen, M.D., Assistant Professor
Internal Medicine

Co-Investigator(s):
Patrick Schloss, Ph.D., Assistant Professor
Department of Microbiology and Immunology

9/1/2011-08/31/2013

The goal of understanding host-microbial relationships during inflammation-related tumorigenesis is to understand host-microbial interactions in the development of intestinal inflammation and cancer.

 

From Mouse Models to human Tumors: K-ras in Advanced and Metastatic Pancreatic Cancer

Principal Investigator(s)::
Marina Pasca Di Magliano, M.D., Assistant Professor
Department of Surgery

11/01/2011-10/13/2012

The overall goal of this development research project is to focus upon targeting K-ras in mouse models of pancreatic cancer. This project will require the identification and development of a K-ras inhibitor for translation.

 

Role of Wnt and c-Met Signaling crosstalk in Aggressive Pancreatic Cancer

Principal Investigator(s)::
Edgar Ben-Josef, M.D., Professor
Department of Radiation Oncology

Meredith Morgan, Ph.D., Research Assistant Professor
Department of Radiation Oncology

Swaroop Bhojani, Ph.D., Research Assistant Professor
Department of Radiation Oncology

11/01/2011-10/13/2012

Role of Wnt and c-Met signaling crosstalk in aggressive pancreatic cancer will explore the role of Wnt and c-Met signaling as biomarkers for aggressive pancreatic cancer. This project may ultimately be useful in identifying prognostic and therapeutic monitoring biomarkers for pancreatic cancer treatment as well as potential drug targets for this problem.



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