“There is an amazing potential for understanding disease if you can have access to human tissues and some of the epidemiological data that goes along with that—it’s really going to be, I think, important for personalized medicine."
- Lawrence Schwartz
The PVLSI is most known for its groundbreaking research and clinical work on breast cancer. Science Director Joseph Jerry and oncologist Grace Makari-Judson of the PVLSI were recently granted $1.5 million from Springfield’s Rays of Hope Foundation to further the Institute’s breast cancer research. Under the auspices of the Institute, funds are being used to develop the Rays of Hope Foundation for Cancer Research and to jump-start promising clinical trials. The Institute, which also specializes in research on diabetes, obesity and apoptosis (or programmed cell death), grew as researchers from UMass Amherst and nearby Baystate Medical Center found they could more quickly and efficiently improve patient outcomes by integrating research in the lab with clinical treatment right from the start.
“If you want to see your project advance, you need to be working with the people that are in a position to help move it along,” explains founding director and UMass Amherst biologist Lawrence Schwartz.
Patient registries are central to the Institute’s research and to the greater mission of personalized medicine. By tracking the individual course, scientists and clinicians can better understand the various subtypes of disease and develop more effective treatments. The breast cancer registry, in particular, has grown rapidly. Jerry explains that the registry allows researchers to look across the thousands of genes within the patient to develop a “signature.” Jerry and his fellow scientists are using gene expression profiling to investigate the ways the disease can manifest.
“In this way you don’t look at just one gene and how it’s expressed, because not just one gene confers risk or resistance, but rather you look at many, many genes. And then you define essentially a portrait of each individual and each individual lesion,” Jerry says.
Jerry, pathologist Giovanna Crisi and other PVLSI collaborators have used the registry to identify high-risk subtypes of atypical hyperplasia, or pre-malignant breast lesions. The team is looking for gene expression signatures that will enable clinicians to more quickly identify the 20 percent of women diagnosed with atypical hyperplasia who are likely to develop full-blown breast cancer. These women could then be treated with therapies to fight the disease proactively.
Within every patient lies a vast and complex biological landscape. Each gene can carry either susceptibility or compensatory pathways that help determine a particular signature. Jerry has been looking at the gene P53 across a host of species for much of his career, describing it as the “most important tumor suppressor gene.” Jerry, a Professor in Veterinary and Animal Sciences at UMass Amherst, began his research career by studying lactation in dairy cows. He was investigating a link between nutrition and cancer, but was drawn instead to the uncharted genealogy behind the disease. It remains a mystery why humans (along with dogs, cats and rodents—animals that live in close proximity with humans) appear to be of the few mammal species afflicted with the disease. He can, however, confidently say that genes like P53 show extraordinary capacity to keep cancerous growth at bay. Deficiencies of P53 are shown to predispose both women and mice to mammary tumors, yet certain strains can resist the malignancy using other genetic pathways.
“In spite of a devastating alteration in the cells of this animal predisposing them to cancer, mammary tumors in particular, there’s something in this other strain that can compensate for it,” Jerry says in reference to one study.
These compensatory pathways could be key to developing new ways to treat breast cancer. Because of the active participation by women undergoing treatment for breast cancer and those participating in breast screening, researchers at the PVLSI are much closer to understanding how genetic makeup directs the disease’s course, and have even discovered a new gene as a result. The gene, which they named Acheron, was discovered in apoptosis research led by Schwartz.
“There is an amazing potential for understanding disease if you can have access to human tissues and some of the epidemiological data that goes along with that—it’s really going to be, I think, important for personalized medicine,” says Schwartz.
Apoptosis, or programmed cell death, refers to the genetic programs that enable the body to eliminate old, damaged and unused cells. When this system stops working, abnormal cells accumulate, which can lead to cancer and other diseases. Adversely, the system also may kick into overdrive and destroy healthy cells, which can lead to diabetes, Alzheimer’s, Parkinson’s and other neurodegenerative disorders. The Institute created the Center of Excellence in Apoptosis Research (CEAR) to house new apoptosis research and offer grant programs.
CEAR recently awarded a $27,900 translational research grant to Amarantus BioSciences Inc. of Sunnyvale, California—a biotechnology company developing new treatments for brain-related disorders. The grant is geared toward exploring the full breadth of Amarantus’s anti-apoptotic therapeutic protein, mesencephalic-astrocyte-derived neurotrophic factor (MANF), which was intended to treat Alzheimer’s. Schwartz, the Principal Investigator on the project, will focus on identifying and testing new clinical targets for the protein and working with Amarantus to move the potentially life-saving therapeutic forward.
Amanda Drane '12