NCI RENEWS $6 MILLION GRANT FOR UMASS MEDICAL SCHOOL CANCER RESEARCHERS 
Renewal allows team of scientists to build upon investigation into genetic control of cancer 

June 28, 2006 

WORCESTER, Mass. - The National Cancer Institute (NCI) has recognized the efforts put forth by a team of University of Massachusetts Medical School (UMMS) investigators by renewing a $6 million program project grant led by Principal Investigator Gary Stein, PhD, Gerald L. Haidak, MD, and Zelda S. Haidak Professor of Cell Biology, professor and chair of cell biology and Deputy Director, UMASS Memorial Cancer Center. The program, Nuclear Structure and Gene Expression, originally funded in 2001 by a five-year NCI grant, focuses on the organization of genes, proteins and factors that control genes in a cancer cell. With this funding renewal, Stein and a multidisciplinary team of researchers will move to comprehend the "dramatic" reorganization of genes and regulatory proteins as it occurs through the onset and progression of cancer, specifically acute myelogenous leukemia (AML) and breast cancer. 

"Initially, it was a project that explored gene regulatory mechanisms that are modified in tumor cells , and what emerged was the realization that it was in fact very clinically relevant," Stein said. "It's now a project that has really made the transition from an exploration of biological control in cancer cells to directly investigating control of early stages of cancer and the subsequent progression of cancer." 

Each gene and regulatory protein is located in a microenvironment within a cell nucleus, and when a gene or protein is not in its correct location, it compromises a cell's function, Stein said. There is a requirement to be in the right place at the right time and location is exceedingly important.  Through the continuing project, which NCI deemed "significant, integrated and relevant," Investigators will examine the architectural structure of genes and regulatory proteins, nuclear microenvironments and the mechanisms used to locate the genes and proteins within microenvironments. They will also explore how regulatory information is delivered to progeny cells during cell division and how to interfere with the process when genes or proteins are not delivered adequately during the early and late stages of cancer. 

Faculty members, fellows and graduate students from the Department of Cell Biology, Department of Cancer Biology, Program in Molecular Medicine as well as other groups within the institution - all members of the UMass Memorial Cancer Center - are contributing to the program's four projects, which will focus on AML and breast cancer. The multidisciplinary team of basic scientists and clinical investigators will study the mechanism responsible for rearranging genes and regulatory proteins in the early stages of leukemia and changes in their organization during the early stages of breast cancer and in late-stage metastatic breast tumors. They will also examine the beginnings of breast cancer and leukemia by attempting to understand the organization of the mitotic apparatus, which Stein describes as the highly arranged system of tracks on which chromosomes travel and distribute to progeny cells during cell division. Furthermore, investigators and scientists will focus on the genes and regulatory proteins' organization and changes when a breast cancer cell metastasizes to bone. Stein said in late stages of breast cancer, the tumor metastasizes to bone, which causes tremendous discomfort and feeds into the tumor's growth.  The team of investigators will apply their insight into reorganization of genes in microenvironments of breast cancer cell nuclei towards developing novel approaches to selectively block the ability of breast cancer cells to move to and grow in bone. 

Clinical insight is critical, and a collaborative approach is required for this project as it encompasses various fields of study from molecular biology, chemistry and biochemistry to structural biology and highly sophisticated microscopy. One investigator has the ability to understand the occurrences at the molecular level, while another can visualize the process at the cellular level. 

From there, the visualized and quantitative findings can begin to be applied to the diagnosis and treatment of cancer. "Looking at cells is a very important component of molecular diagnosis," said Stein. "The initial diagnosis of a tumor is what is seen under a microscope. Now we're able to obtain explanations for the changes in cellular organization one sees in cancer." Taking on such a program project would not be possible without the other disciplines involved, Stein remarked. "We have the ability for people to work in teams, where you can develop multidisciplinary approaches with individuals who have different skill sets and people who understand problems from a basic science standpoint and a clinical standpoint," Stein said. 

"It's a project that could not have been developed if we couldn't function in a collaborative manner, and that's really the hallmark of this institution." 

In addition to Dr. Stein, the principal investigator for the grant, other faculty members highly involved include: co-principal investigator Janet L. Stein, PhD, professor of cell biology; André J. van Wijnen, PhD, associate professor of cell biology; Anthony N. Imbalzano, PhD, associate professor of cell biology; Jeffrey A. Nickerson, PhD, associate professor of cell biology; Stephen J. Doxsey, PhD, professor of molecular medicine, biochemistry & molecular pharmacology and cell biology; Jane B. Lian, PhD, professor of cell biology; and Lucia R. Languino, PhD, professor of cancer biology, cell biology and radiation oncology.

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About UMMS
The University of Massachusetts Medical School is one of the fastest growing medical schools in the country, attracting more than $174 million in research funding annually.  A perennial top finisher in the annual U.S.News & World Report ranking of primary care medical schools, UMMS comprises a medical school, graduate school of nursing, graduate school of biomedical sciences and an active research enterprise, and is a leader in health sciences education, research and public service.

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Contact: Nicole Soucy, 508-856-2000, ummsnews@umassmed.edu