Robert Weiss, assistant professor
Department of Biomedical Sciences, College of Veterinary Medicine
By Clare Ulrich
"Of the approximately 30,000 genes in the mouse genome, 99 percent have a matching sequence in the human genome,"says Robert Weiss, who in fall 2002 joined the faculty of the Department of Biomedical Sciences in the College of Veterinary Medicine. "And the proteins encoded by these related gene pairs are 80 percent identical on average."
Discoveries in life sciences and genomics continue to reveal how much we have in common with all life forms, right down to genetic makeup. The new understanding of life we are gaining is revolutionizing the treatment of human disease and making disease prevention much more achievable.
With long-term goals like these in mind, Robert Weiss investigates how genomic stability is preserved, that is, how cells accurately replicate DNA and respond to DNA damage.
"DNA is made up of four different nucleotides that are paired together in
the double helix," he explains. "Each mammalian cell has about six billion
of these base pairs, and each time a cell divides it has to copy each of these
pairs with extreme accuracy or mutations will arise. It's quite remarkable when
you think about it. The pathways for maintaining genomic stability are important because
if that stability is lost, then the mutation rate of cells is increased,
and that's what drives tumorigenesis (formation of tumors), developmental defects,
and other problems in mice and humans."
Weiss uses the mouse as a model system.
"Basically all the human genes we're interested in are also there in the mouse.
The physiology of the mouse is so similar to humans that we believe it's the best
system for creating accurate animal models for human diseases. And cancer is
one of those diseases."
Sophisticated genetic techniques enable Weiss to target specific genes in the mouse,
disrupt them, and observe the consequences.
"At first we were able knock out (remove) a given gene to see how loss of the gene would affect the entire organism. But if a gene proved to be essential, the mouse wouldn't survive. So that technique was somewhat limited. Now we can knock out genes of interest in given tissues, such as the mammary gland. In our studies, we produce genomic instability specifically in the mammary gland to study how this affects mammary gland development and whether this genomic instability promotes tumorigenesis. Then we look at how relevant this information might be to breast cancer. It's very critical to have these kind of accurate replicas of human diseases to understand how a disease arises and to develop effective therapies."
With the completion of the human genome, scientists are beginning to understand how biology works at the whole genome level-the way genes organize into pathways and networks that interact. The next step, predicts Weiss, is functional genomics, or studying genes and their functions at the whole genome level. More accurate disease diagnosis will be one practical application of these discoveries. Physicians will also be able to identify individuals who have mutations in genomic pathways that might predispose them to developing tumors. And the kind of therapy an individual would respond to most successfully could be determined.
"If we understand how cells respond to DNA damaging agents, including anti-cancer drugs like cisplatin and adriamycin that are currently used to treat human cancers, then we might be able to better predict how a cancer cell, or surrounding normal cells, would react to chemotherapy. We have visions someday, when these pathways are better understood, of being able to design effective therapies for individual tumors."
Weiss believes Cornell is already leading the way in genomics, which is one reason he was attracted to the university. Other reasons include the Vet College's number one rank in U.S. News and World Report in 2003. "It has a great reputation that is well deserved. And historically Cornell has strengths in many, diverse areas-not just the biological sciences but chemistry, physics, engineering, etc. So collaborative interactions can really be developed. And the facilities are clearly a draw," he emphasizes.
"In addition, the existence of the New Life Sciences Initiative shows a commitment on the part of Cornell to these technologies. It's an important investment in the future, and it makes it clear to me-somebody new coming in-that there are going to be a lot of other new people on their way as well. I'm also impressed that a junior person like myself can get so involved in a university-wide initiative. Everybody has Cornell's best interests in mind rather than their own personal agendas, and they are open to suggestions from a young person like me. I feel I can make an impact here."
Weiss also likes having the opportunity to get students excited about science and to help shape their futures. He currently has two undergraduates working in his laboratory, and another arrives this summer.
"All faculty are expected to teach and to do it well. I think that's important. As a scientist I feel that I am not only making discoveries in the laboratory that contribute to the life sciences, but I am also making significant, long-lasting contributions by training and mentoring future scientists."
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