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Looking for a Slam Dunk in Cancer Research

By Greta Petry (October 8, 2004)

From left to right:Chittibabu Guda, Igor Kuznetsov, Scott Tenenbaum, Paulette McCormick, Julio Aguirre-Ghiso, Thomas Begley, and Doug Conklin.

From left to right:Chittibabu Guda, Igor Kuznetsov, Scott Tenenbaum, Paulette McCormick, Julio Aguirre-Ghiso, Thomas Begley, and Doug Conklin.

Their work is full of complex scientific terms like “alkylating agents” and “metastatic disease.” Yet several bright young scientists at UAlbany’s Gen*NY*Sis Center for Excellence in Cancer Genomics (GCECG) at the east campus describe a few reasons for working in cancer genomics that we can all understand.

Tom Begley, 33, joined the University at Albany this year from the Massachusetts Institute of Technology (MIT). He earned his Ph.D. from UAlbany in 2000, and studies how a class of chemotherapeutic medicines called “alkylating agents” works in different types of cancer cells.

“One of the main reasons I have worked in cancer biology is that my father died of lung cancer and I wanted to get a better understanding of how this could happen at the molecular level,” Begley said. “I wanted to probe mechanisms that could help eradicate this horrible disease.”

Julio Aguirre-Ghiso, 34, who won a prestigious Waxman grant this summer, worked pro bono for a cancer research lab in a public hospital while still an undergraduate. There, he interacted daily with clinicians and saw “the devastating effects of the disease [cancer] on patients, particularly on children…” This led him to the research area he studies today, tumor metastasis, which is how a tumor spreads from one part of the body to another. Aguirre-Ghiso earned his master’s degree and Ph.D. from the Uni-versity of Buenos Aires, Argentina, and did his post-doctoral training at the Mount Sinai School of Medicine of New York University, sponsored by a Charles Revson Foundation Fellowship.

Begley and Aguirre-Ghiso are two of a growing core group of scientists in UAlbany’s Department of Biomedical Sciences in the School of Public Health forming part of the GCECG. The cancer center is being built under the direction of GCECG Director and UAlbany Professor of Biological Sciences Paulette McCormick.

Ranging in age from 33 to 40, these energetic and sociable scientists are working on the cutting edge of cancer research. Three of them joined UAlbany a year ago, and three more were hired this fall. Hired at the assistant professor level, they include: Scott Tenenbaum, 39, who earned a Ph.D. from Tulane and did a post-doctoral fellowship in microbiology at Duke, where he helped with pioneering work in the new field of ribonomics; Doug Conklin, 40, who recently moved from Cold Spring Harbor Laboratory on Long Island, has two grants to study breast cancer, and recently co-authored a paper in the journal Nature, one of the world’s leading scientific publications; Chittibabu Guda, 35, a bioinformatics specialist who joined UAlbany from the University of California, San Diego, and earned his Ph.D. from Auburn University; and Igor Kuznetsov, 34, who earned his Ph.D. from the Mount Sinai School of Medicine, NYU, and who uses computational methods to analyze genomic data.

Housed at the east campus in proximity to each other, the scientists are not all work and no play. Some play basketball each week with colleagues in chemistry and biology. Several were attracted to the Capital Region’s high quality of life, and said this is a good place to raise a family. They look forward to having more space in the new cancer research facility slated to open in 2005 at the east campus, and they already are pooling their talents and knowledge while pursuing their own independent research.

McCormick said, “We have learned a tremendous amount about the biology of cancer in the past two decades, but it has not really translated into very effective changes in treatment. What the new Gen*NY*Sis center in cancer research is focused on, as opposed to the old model of one gene, one type of cancer, is a new model of using high-throughput, multi-modal approaches that apply to many different cancers with many different causes and therefore rapid translation of basic research findings into clinical treatments for multiple cancer types and the maximum number of patients. I think the value of this approach is proven by the fact that all our new faculty who have only been here for a single year are already funded, a success rate unequaled in most of the top 10 universities. In fact, half of the new faculty already have more than one grant, and I can confidently predict that the others will soon be at that level.”

The cancer research center also offers important research opportunities for exceptional UAlbany students. Several post-doctoral fellows, graduate students, undergraduates, and even high school students are currently gaining experience with the latest methods in cancer research at the center. In addition, Kuznetsov and Guda are seeking talented graduate students interested in doing bioinformatics research.

In describing his research area, Aguirre-Ghiso said, “More than half of cancer patients will die from metastatic disease — that is, cancer that has spread throughout the body — that develops months, years, or even decades after an initial tumor is removed. Our research is aimed at studying the mechanisms that determine whether cancer cells that spread throughout the body will continue to proliferate and form life-threatening, large, secondary tumor masses, or become dormant and harmless...We hope our work will develop into therapies that could convert inoperable growing metastasis into dormancy, allowing the patients to survive and live a long life with an inactive lesion and also to develop therapies to eradicate dormant tumor cells.”

Tenenbaum said this core group of professors studying cancer has produced an atmosphere that is “very co-dependent and highly productive.” Joining the cancer center gave him “an opportunity to be part of something with great potential, at the very beginning stages.” He added, “Overall, I have had an opportunity to play a role in many things that I doubt most junior faculty members have had a chance to experience.”

At Duke, Tenenbaum helped pioneer genomic-based technology that helped open up a poorly understood field of biology: post-transcriptional gene expression.

“The methods I developed are wonderfully complementary to Dr. Aguirre-Ghiso’s tumor metastasis and dormancy models, as well as to Dr. Conklin’s shRNA methods,” Tenenbaum said. “For example, we are presently applying my ribonomic methods to Dr. Aguirre-Ghiso’s tumor dormancy model and confirming our data by using Dr. Conklin’s shRNA library to knock down identified genes of interest. Meanwhile, both Drs. Kuznetsov and Guda help in the bioinformatics analysis and identification of which genes to focus on. We can then add Dr. Begley’s chemotherapeutic drugs to the mix and study their effect on cellular function.”

Tenenbaum’s research, funded by NIH, has the potential to help explain how similar tumors can behave very differently with respect to treatment. He recently won a new $400,000 NIH grant to develop technology for the genome-wide identification of regulatory elements in the human genome.

He said, “My research could be useful in developing more specialized and tailored cancer treatment therapies as well as anti-cancer drugs.” Tenenbaum lives in Bethlehem with his wife, a pediatrician at St. Peter’s Hospital, and three sons, ages 9, 6, and 20 months.

In addition to funding from the NIH, Begley won a $200,000 James D. Watson Investigator award from the state this summer for promising early career scientists. He is interested in why some cancers can be put into remission using certain chemical compounds, while on others there is no effect.

Begley finds UAlbany’s plan to invest heavily in nanotechnology, information technology, and cancer genomics to be “very progressive,” and he noted these three core areas are also important at MIT and other advanced research environments.

Kuznetsov, who joined UAlbany this fall with Guda and Begley, said, “My research is directed towards developing efficient bioinformatics tools by integrating statistics, unsupervised and supervised classification methods, high-performance computing, and information technology and applying these tools to genomics research…My goal is to bring computational studies closer to reality and, hopefully, create better ones by working with wet-lab biologists here at the cancer center.”

Guda said, “Bioinformatics research is the natural choice of interest due to my interdisciplinary educational background in molecular biology and computer
science. Contributing my drop to the ocean of knowledge required for the treatment of diseases like cancer is challenging as well as rewarding both professionally and personally.”