With a $10.2 million grant from the state's tobacco fund settlement, the Case Western Reserve University School of Medicine and a consortium of Ohio research institutions and companies plan to make the state a leading center in the nation for genetics research of gastrointestinal (GI) cancers.

The partners also see tremendous potential for biotech commercialization efforts for the state as a result of the program the funds will support.

CWRU received the grant from the Ohio Biomedical Research and Technology Transfer Commission (BRTTC) for a major program to study, diagnose, manage and prevent GI cancers. CWRU was the only Northeast Ohio institution to receive funding, and the National Academy of Sciences (NAS) reviewers called its proposal the strongest of the 13 submitted. The state's funding will be matched by the participating institutions.

Joe Nadeau, the James H. Jewell Professorship in Genetics at CWRU and principal investigator on the grant, will lead a consortium, including Ohio State University; Cleveland Clinic Foundation; Research Institute of University Hospitals of Cleveland; Ireland Cancer Center at University Hospitals of Cleveland and CWRU; the University of Cincinnati; and nine Ohio-based companies, including Athersys Inc. in Cleveland, Hitachi Medical Systems America Inc. in Twinsburg, NineSigma in Beachwood, Philips/Marconi Inc. in Mayfield Village and Zalen LLC Inc. in Novelty.

The announcement was made by the commission at a meeting in November.

According to the scientific review conducted by the NAS, "the discoveries anticipated to arise from this project are likely to increase the arsenal of diagnostics and treatment related to colon cancer. In addition, as a result of this project, Ohio may become a major center of studies related to colon cancer and a major source of new commercial products (and jobs) related to its diagnosis and treatment."

The NAS reviewers concluded that the CWRU project was the strongest of the 13 proposals reviewed because it included "the relevance of gastrointestinal cancer as an important health issue for Ohioans, the soundness and quality of the scientific research plan, the scientific credentials of the principal investigators, the financial and in-kind contributions of the members of the proposed consortium and the cogency of the business plan."

In addition, the reviewers wrote that "the likelihood of creating valuable commercial products-including unique mouse resources and models, a cancer biorepository resource, cancer-related genes and gene-products as targets for pharmaceutical development and new diagnostic-imaging and research tools-is substantial. The potential creation of new jobs and the foundation of a critical mass of researchers and companies engaged in the use of novel technologies and resources for the study of GI and other cancers are compelling reasons to endorse this proposal."

Called "Genetics of Gastrointestinal Cancers," the program builds on the work of first-rate investigators in Ohio. It will use gene discovery in mice to understand mechanisms of human disease and to develop and commercialize possible treatments. In parallel, the program will take gene discoveries in humans and study them in mice to research the underlying biologic mechanisms in disease. The program is expected to generate information that will be of interest to pharmaceutical companies.

"In addition, the program funding will establish resources, infrastructure and expertise that can be used to obtain federal grant support at participating institutions, to enhance the viability of Ohio-based companies and to improve the health of Ohioans," Nadeau said.

The research program will establish three core facilities: a biorepository that will collect tissues essential for gene discovery, a state-of-the-art mouse clinic and bioimaging facility and a mutant mouse resource to look at genetic mutations involved in cancer.

"As the reviewers recognized, these three components will be unique, individually and collectively, and will place participating investigators and institutions at the forefront of research, diagnosis, treatment and prevention of various GI cancers," Nadeau said.

CWRU, UHC, CCF, OSU and U of Cin. will be individually responsible for collecting and locally managing cancer-related information and materials, which will be shared with consortium investigators at the participating institutions. The mouse clinic and bioimaging facility will be located at CWRU, with several key partner companies (3D Imaging, Zalen, Hitachi America, USA Instruments). The mutant mouse resource will include genetically engineered mice at the U. of Cin. and its partner Genomatix, and induced mutant mice, including mutations that suppress cancer susceptibility, made at CWRU.

"Not only will this help find new therapies for colon and other GI cancers to help Ohioans and all Americans, it should also help energize the local and state biotech economy," said Jerold Goldberg interim dean of the School of Medicine.

Athersys will be an important option for commercialization. Commercialization also will be coordinated with The TIIME program at CWRU; Edison Biotechnology; and NineSigma, a local company that specializes in facilitating and negotiating academic and corporate partnerships. Faculty participating in this project are among the leaders in their fields and include: Gil Van Bokkelen, co-principal investigator; president of Athersys Inc.; Graham Casey, project investigator and member of the associate staff in the Department of Cancer Biology, Cleveland Clinic Foundation; Albert de la Chapelle, project investigator and professor and director of the Human Cancer Genetics Program, OSU; James M. Church, project investigator, professor of surgery at OSU and staff colorectal surgeon at CCF; Thomas Doetschman, project investigator; professor of molecular genetics, U. of Cin.; Jeffrey L. Duerk, project investigator and advisory committee member, professor of radiology at CWRU and director of physics research in the department of radiology at UHC; Charis Eng, project investigator, co-principal investigator at the OSU site, William C. and Joan E. Davis Professor of Cancer Research, associate professor of medicine and director of Clinical Cancer Genetics Program at OSU; Cecilia M. Fenoglio-Preiser, project investigator and MacKenzie Professor and Director of Pathology and Laboratory Medicine at the U. of Cin.; Jeffrey T. Glass, project investigator; Joseph F. Toot Jr., Professor of Engineering and co-director of the Institute for the Integration of Management and Engineering at CWRU; Joanna L. Groden, project investigator, co-principal investigator at the U. of Cin. site and associate professor in the department of molecular genetics, biochemistry and microbiology at theU. Of Cin.; Sanford D. Markowitz, project investigator, Ingalls Professor of Cancer Genetics and professor of medicine at CWRU and medical oncologist at the Comprehensive Cancer Center of CWRU and UHC; Mehran Mehregany, George S. Dively Professor of Engineering and director in electrical engineering and computer science at CWRU and founder and CEO of NineSigma; George R. Stark, project advisory committee member, professor of genetics at CWRU and the Distinguished Scientist and former chair at the Lerner Research Institute of CCF; Georgia L. Wiesner, project investigator, assistant professor of genetics and medicine at CWRU and acting clinical director at the Center for Human Genetics of CWRU and UHC; James K.V. Willson, project investigator and advisory committee member; Robert W. Kellermeyer, professor of oncology at CWRU and director of the Comprehensive Cancer Center at CWRU and UHC; Joseph E. Willis, project investigator, assistant professor of pathology at CWRU and staff pathologist at UHC.

The BRTTC and its awards are funded by the 1998 Tobacco Master Settlement Agreement.

The BRTTC program is a key component of Governor Bob Taft's Third Frontier Project, a sweeping 10-year plan to set Ohio's course for national leadership in the high-tech economy of the 21st century.