UAlbany's Life Sciences Research Initiative:
On Genes, Proteins and Genetically Engineered Mice

“A major goal of life sciences research is to discover the genetic roots of disease and to design new treatments.” Paulette McCormick

Editor’s Note: Now that scientists have decoded most of the human genome, they are tapping the gold mine of information in multi-faceted research efforts to unravel the molecular mysteries of life — and disease. At the University at Albany, researchers are engaged in this exciting quest on a number of different fronts. University biologist Paulette McCormick, the director of the University’s Center for Comparative Functional Genomics, talked with UAlbany magazine’s executive editor, Mary Fiess, about some of the work under way and the significance of the University’s new $100 million Life Sciences Research Initiative.

UAlbany magazine: When the University launched its $100 million Life Sciences Research Initiative last year, more than one person asked whether the term “life sciences” was just a fancy name for biology. What do we mean when we refer to the life sciences?

Paulette McCormick: The term “life sciences” certainly means something much greater than biology per se. It encompasses chemistry, physics, environmental sciences, as well as areas of psychology, anthropology, earth sciences, computer sciences. By using the term “life sciences,” we are highlighting the importance of interdisciplinary research in addressing today’s scientific challenges.

UAlbany: And what do we mean when we talk about our “initiative?”

McCormick: We’re referring to the overall investment the University is making in facilities and people to advance the interdisciplinary explorations that will, for example, help us understand cancer and design better treatments. The new Life Sciences Research Building going up on campus will have the kind of laboratory space and equipment necessary for such research, and the University has begun recruiting faculty researchers with the kind of expertise to complement and advance our programs in such areas as genomics, proteomics, and bioinformatics. The initiative is being funded by $80 million in state and research funds and another $20 million that is being raised in private support.

UAlbany: Why does it make sense for the University at Albany to become a center for research in the life sciences? What are the resources the University and the region already have in place?

McCormick: Universities are at the forefront of technology and research. The sequencing of the human genome has led to an explosion of information that can be exploited by life scientists for public benefit. The University at Albany and this region have a tremendous research infrastructure. Our own campus resources include our School of Public Health and its Center for Public Health Preparedness, our Center for Comparative Functional Genomics, the Center for X-Ray Optics, the Center for Biochemistry and Biophysics, the School of NanoSciences and NanoEngineering, and more. All our efforts are also supported and complemented by initiatives at such area institutions as Albany Medical Center, Rensselaer Polytechnic Institute, the Veterans Administration hospital, with which we are working very closely as a partner, and also the Wadsworth Center. So we have a tremendous infrastructure that is critical to pulling together all of this information and using it to benefit society.

UAlbany: As even a partial list of UAlbany’s research centers and schools suggests, the scope of life sciences research is wide-ranging. What are some of the projects being tackled by University faculty?

McCormick: At our Center for Comparative Functional Genomics, we have projects related to cancer and metastases biology, as well as mammalian developmental genetics. One project funded by the National Institutes of Health focuses on the use of retinoids — natural and synthetic derivatives of Vitamin A — in cancer therapy. In another project, we are investigating the role of cell-surface lysosomal associated membrane protein (LAMP) in tumor progression and metastases – the latter of which causes 90 percent of deaths from solid tumors. We are theorizing that an antibody recognizing cell surface LAMP might very well block metastatic cells from spreading, thereby greatly decreasing cancer mortality.
Faculty at our Center for X-ray Optics are studying new ways of focusing X-rays for the treatment of surgically intractable cancers like brain cancer. Researchers at our School of NanoSciences and NanoEngineering are working on biosensors and developing a device for faster detection of tuberculosis.
Other areas of research include efforts to foil the functions of cells that cause blockages in heart arteries, and work to understand tendon development, which we hope will lead to improved treatment of tendon injuries. We are also analyzing a newly discovered repressor protein whose mutations could account for high levels of spontaneous abortions that occur early in human pregnancy.

UAlbany: What is the significance of the Mutant Mouse Regional Resource Center (MMRRC), one of only four in the U.S.?

McCormick: The Mutant Mouse Regional Resource Center is funded by the National Institutes of Health (NIH) and is a joint undertaking of UAlbany’s Center for Comparative Functional Genomics and an industrial partner, Taconic Biotechnology, Inc. The basic idea behind these centers is to enable researchers to make the best possible use of a very valuable and critical resource in life sciences research, namely, mice with specific mutations. As scientists’ closest working model to the human being, the mouse is widely used by researchers to explore genetic processes, particularly the processes that cause disease. But one problem has been that every different research group would breed their own mutant mice in their own laboratories and then, when the specific project was completed, the strain would often die. So a valuable resource that could be used in many other projects was gone. Someone, for example, might have studied Alzheimer’s disease and then, in a later project, perhaps on Alzheimer’s or a neurological aspect of the brain, someone else would want the earlier strain, but would have to get it bred again. Now researchers can send the strains they’ve developed to the mutant mouse centers, which, in turn, can clean them of pathogens and preserve the eggs so that others who need them can have that specific type.

UAlbany: Are there specific ways this center helps and complements UAlbany research?

McCormick: For one thing, we are doing some novel research on the mouse in order to maximize the value of the mutants. In a project on global gene expression, we are using microarray technology to look at all the genes that are being expressed in a cell at any one time, and we are comparing expression in one strain of mice to expression in another strain of mice to see how much variation there is between those strains. We are interested in how much variability there is so we can begin to extrapolate how much variability there will be in humans when we get to individualized medicine. We are comparing gene expression in the liver versus the kidney versus the brain to see how much is tissue -specific. For example, in cancer, a lot of our treatments are the same, whether it’s kidney or liver cancer. But cancer of different tissues may require different treatments, and this research will help us better understand what will work. We are also preparing to look at young versus old mice in order to see how gene expression changes with aging.
Mice are helping us answer other questions, as well. Researcher Rick Cunningham, for example, is looking at mutations in the DNA repair pathway and how those mutations affect the development of different diseases and how those mutations can be targeted to prevent disease. From his work with mice, we can begin to extrapolate to human DNA repair pathways. In another project, one of my students is looking into combination therapies for cancer and how they affect global gene expression in mice.

UAlbany: What are the kinds of tools necessary to advance life sciences research?

McCormick: The effort to decipher molecular mysteries requires highly sophisticated — and expensive — equipment. When CCFG was established, New York State provided $5 million in funding that allowed our center to purchase and staff state-of-the-art core research facilities. And just this year, CCFG teamed up with Myomatrix Molecular Technologies, a biopharmaceutical company focused on treatments for cardiovascular disease, to acquire a Micromass Q-ToF2 mass spectrometer, the only one of its kind in the Capital Region. The Q-ToF2 mass spectrometer is critical for the separation, identification and sequencing of proteins. In short, we have acquired sophisticated high through-put instrumentation, i.e., DNA sequencers, synthesizers, microarray analysis equipment, flourescence-activated cell sorter. High through-put is very critical. Instead of sequencing one gene over three months, we now can sequence a hundred genes in a day. We are currently using this in multiple ways and expect to soon use it to do comparisons of protein profiles. By comparing protein profiles from tumor cells and the adjacent normal cells, we can identify the proteins that are differentially expressed between tumor and normal cells and therefore might potentially represent new drug targets.

UAlbany: What are the benefits of research in these areas for the University and the world beyond the campus?

McCormick: Clearly, a major goal of life sciences research is to discover the genetic roots of disease and to design new and or more effective treatments. Plus, In a more general sense, we want to improve the quality of life on this planet. The life sciences can help us fashion high-tech solutions to problems like pollution. Perhaps we can design bacteria to destroy plastics that would never be biodegradable. In the wake of September 11, we are also looking for the ways the life sciences can also help counter bioterrorism.
Beyond that, the research at UAlbany and at other institutions is advancing the economic vitality of this region. A strong academic infrastructure is at the core of all national clusters of the biotechnology industry.

UAlbany’s East Campus (highlighted in the spring 2002 UAlbany issue), where the Center for Comparative Functional Genomics and the School of Public Health are located, has become a thriving center for biotechnololgy and biomedical sciences in the Capital Region, and our new initiative will help move our University and region to the next level.