M. D. Anderson wins $8.3-million to research environmental causes of major diseases

An $8.3-million federal grant to The University of Texas M. D. Anderson Cancer Center Science Park - Research Division addresses the complex interplay between such varied factors as genetics, diet, and environmental exposure to toxins that cause cancer, asthma, diabetes, cardiovascular and other diseases.

The five-year renewal grant from the National Institute for Environmental Health Sciences (NIEHS) - one of only 23 awarded nationally - comes as the Science Park - Research Division this month celebrates its 30th year detecting the origins of cancer at its labs in Central Texas. The grant continues funding of the 10-year-old Center for Research on Environmental Disease (CRED) and expands its scope.

"This center is very broad in its approach," says John DiGiovanni, Ph.D., head of both the center and the M. D. Anderson Department of Carcinogenesis, which is based at the science park. "We study everything from the molecular mechanisms of how environmental agents cause toxicity and carcinogenesis to how diet affects our responses to environmental exposures and the interactions between genes and these external factors."

For example, the center's expertise on diet and energy balance addresses obesity, which is a risk factor for cancer, diabetes and cardiovascular disease, DiGiovanni notes.

The NIEHS center is an important part of the $14.5 million in annual total grant funds awarded to the science park, whose principal focus is understanding how normal cells become cancerous.

"Understanding carcinogenesis - how cancer begins - provides the basis for improving therapies and even more excitingly offers a realistic hope of someday preventing disease outright," says M. D. Anderson Cancer Center President John Mendelsohn, M.D.

"From day one, our Science Park - Research Division has focused the expertise of diverse scientific disciplines on this vital area of research. The NIEHS renewal recognizes accomplishments by our scientists and their ability to continue pushing the boundaries of what we know about the causes of cancer," Mendelsohn says.

A central goal is to understand risk factors and work toward cancer prevention. "One long-term goal is to identify genetic characteristics that pose a high risk for cancer. Then we want to offset that genetic risk by altering a person's diet, for example," DiGiovanni says.

Perhaps the most famous research out of the science park showed how a carcinogen in cigarette smoke damages a tumor-suppressing gene, the first demonstration of molecular damage caused by smoking.

A current line of research examines how exposure to environmental hormones at crucial times during development can reprogram genetic functions that raise risk for cancer in adulthood. (Please see Research Highlights).

CRED Renewal The NIEHS grant provides core research infrastructure for four areas of inquiry: environmental and molecular epidemiology; mechanisms of environmental carcinogenesis; diet, energy balance and environmental disease risk; and genetics and epigenetics of early life exposures.

Collaborative research is enhanced and expanded. "A new feature of the center is a much greater focus on translational research," DiGiovanni says. Translational research is the bridge between basic science research that discovers fundamental molecular aspects of disease and clinical research that carefully tests new therapies in patients.

Most of the center's work is in preclinical translational research, the testing of lab findings in animal models. Collaboration with the M. D. Anderson Department of Epidemiology and a new connection to the University of Texas School of Public Health in Houston provide ties to population research.

Clinical connections include participation in three M. D. Anderson Specialized Program of Research Excellence (SPORE) in prostate, head and neck cancer, and in gynecologic cancers. SPORE programs are a National Cancer Institute initiative to encourage more efficient translation of laboratory findings to clinical application.

The school of public health, part of The University of Texas Health Science Center at Houston, adds expertise in monitoring an individual's personal exposure to airborne toxins and carcinogens. "We will be looking at air pollution issues. Our colleagues there focus on asthma and cardiovascular disease, so we will be broadening the scope of environmental diseases under study at the center," DiGiovanni says.

The CRED grant also includes the Center for Molecular and Cellular Toxicology, a joint interdisciplinary center with the University of Texas at Austin to conduct basic toxicology research.

Educational Outreach The Community Outreach and Education Core (COEC) of the CRED has an educational mission to inform audiences about the causes and prevention of environmental disease. Through a variety of programs and activities, the COEC functions as a communication conduit between center researchers and the communities of Central Texas, public health workers and policy makers. These include:

• Community forums, such as the one held on the contamination of Barton Springs Pool (Is Barton Springs Pool Safe?) that provide information to the public about matters of environmental concern.
• Summer research internships for undergraduate, high school and public health students.
• Testimony and working sessions with legislative committees focused on nutrition and obesity, environmental hazards and K-12 education.
• The MIDAS (Models of Implementation and Dissemination of environmental health science Across Subjects) Project, a $1.5 million Science Education Partnership Award targeting the K-12 educational community. MIDAS includes the Environmental Health Sciences Summer Institute for K-12 Educators, held annually at the Thompson Conference Center.
• Online environmental disease prevention and educational sites for a variety of target audiences. (veggie-mon.mdanderson.org and SCREAM.mdanderson.org)

Smithville and Bastrop County ties The Science Park-Research Division at the Virginia Harris Cockrell Cancer Research Center is celebrating its 30th anniversary with a gathering of staff, faculty, friends, supporters and alumni of the center on April 21.

The Science Park-Research Division was the brainchild of M. D. Anderson's first president, R. Lee Clark, M.D., who envisioned a major research in environmental sciences for the Smithville area during the early 1960s.

Clark worked with the Texas Department of Parks and Wildlife, the City of Smithville, Bastrop County and the Texas Legislature to transfer 717 acres of land in Buescher State Park to the University of Texas.

As the park developed, it came to focus on the causes of cancer, with special attention to environmental factors. M. D. Anderson's study section in carcinogenesis moved to the new facility in April 1977 as the Department of Carcinogenesis, its multidisciplinary structure was a pioneering departure from the organizational practices of the times that foreshadowed an increasingly common practice in recent years.

"Local support has always been a wonderful aspect of the SPRD," DiGiovanni notes. "Friends of the Science Park provide both moral support and financial help for us and we greatly appreciate their efforts. Friends of the Science Park have been instrumental in our celebration of our 30th anniversary."

The Virginia Harris Cockrell Cancer Research Center at The University of Texas M. D. Anderson Cancer Center

Research Highlights

• Discovery of a Direct Link between Smoking and Lung Cancer. Researchers showed that bronchial epithelial cells treated with BPDE (a carcinogen in cigarette smoke) exhibited DNA damage in the P53 tumor suppressor gene, a major target gene for cigarette smoke-induced lung cancer. These results provided the first direct link between a chemical carcinogen in tobacco smoke and human lung cancer.
• Discovery of the T cell Receptor. T cells are immune cells that protect against infection and cancer. Researchers discovered the T cell receptor, a molecule expressed by T cells that activates their function. This discovery paved the way for a greater understanding of the role of the immune system in detecting and eliminating infectious diseases and cancer.
• Discovery of a Candidate Melanoma Suppressor Gene in a Fish Model. Using a novel fish model to investigate the role of UV in causing melanoma, a tumor suppressor gene related to human melanoma susceptibility was discovered. This discovery connects research using this unique animal model with a tumor suppressor gene important to melanoma risk in humans.
• Early Life Exposure to Environmental Chemicals May Increase Cancer Risk Later in Life. Researchers have uncovered a potential reason why some people who are genetically predisposed to hormone-dependent cancers develop the disease as an adult, while others who are similarly susceptible do not. Their studies showed that exposure to pharmaceutical estrogen during fetal development can permanently "reprogram" tissues in a way that determines whether tumors will develop in adulthood.
• Discovery of a Potential Skin Cancer Prevention Target. Scientists identified a protein, called Stat3, that is required for the development of skin cancer. This finding could lead to new ways to prevent skin cancer before it starts. Further research revealed a central role for Stat3 in the interactions between skin and the immune system that cause psoriasis.
• Mild Forms of Calorie Restriction are Effective at Preventing Cancer in Genetically Predisposed Animals. Researchers discovered that adult-onset calorie restriction and a one day/week fast increased longevity in mice genetically predestined to develop fatal tumors due to p53 deficiency. These studies indicate that even mild forms of calorie restriction in adults may be an effective means of preventing or reducing risk of cancer, especially in genetically predisposed individuals.
• "Backward" DNA causes genetic instability that can lead to cancer. When otherwise normal DNA adopts an unusual shape called Z-DNA, it can cause the kind of genetic instability in "hot spots" of the genome associated with cancers such as leukemia and lymphoma. These findings opened a new field of inquiry into the role of DNA shape in genomic instability and cancer.