Cancer Center continues research with $2.1 million grant
ANDREW THAGARD
Assistant News Editor
For an organization pioneering new methods to diagnose and treat cancer, the Walther Cancer Research Center calls little attention to itself within the Notre Dame community. The organization is spread out throughout campus, and because the Center has no central building, faculty members use their own laboratories for research.
"I don't think if you think of Notre Dame and the College of Science you think cancer research," said Rudolph Navari, Center director.
But this perception may soon change with the arrival of an additional $2.1 million in grant money from the U.S. Department of Defense. The money, according to Navari, will be used to fund new projects and expand on additional research including studies focusing on cancer growth and development, genetics and drugs used in cancer treatment.
From humble beginnings
Today's Walther Cancer Research Center arose from rather quaint beginnings —beginnings so quaint, it seems, that the Center's directors cannot agree on when it was founded.
According to Francis Castellino, the Center's first director and current head of the Center for Transgene Research, the organization was established "in a small way" in 1995 with a 50,000-60,000 dollar grant from the Walther Cancer Institute of Indianapolis. The Institute's grant was designed to establish a basis for an organization that would effectively seek research grants, like the one given by the Department of Defense.
Since its founding, the Center has grown rapidly. What started as an organization for which a few Notre Dame faculty members researched under, has expanded to include 30 members of the faculty and numerous graduate student researchers. Today the Center boasts a multi-million dollar budget that allows it to focus on pre-clinical cancer research using state of the art facilities.
"The scientific community is starting to realize the stuff that goes on here," Navari said. "We feel that at this point, in certain areas of cancer research, we're as good as anywhere in the country — including schools with medical schools."
What adds to the uniqueness of the Walther Cancer Research Center, according to Navari, is the close relationship researchers enjoy from the different academic departments.
Researchers from the University's departments of Chemistry, Biochemistry and Biology collaborate on research focusing on four main programs. These programs include a transgene group led by Castellino, a cell biology group and a drug design group led by Paul Helquist. The groups include faculty from the three departments and may work on different aspects of the same research project. Even the laboratories used for the Center's research are spread out around campus.
"Many times people will work in their own labs independently," Navari said. "We think that for cancer research [if people] work together, more progress will be made in a shorter period of time."
This spirit of collaboration, however, doesn't stop within University departments. The Center also works with Purdue's school of pharmacy in drug development and with Indiana University and Michigan University on product testing. In addition, IU medical students studying at the Notre Dame branch have the option of earning a dual M.D./Ph.D through both schools and research opportunities through the Center.
The organization also selects a limited number of Notre Dame undergraduate researchers and the Center for Transgene Research recruits students from German and Canadian universities for undergraduate assistant positions.
The road to drug development
Researchers from the Drug Design Group are busy studying compounds that effect cancer cells and may be used in diagnosis and treatment.
Currently, the group is working with antigens that are capable of binding to the outer membrane of prostate cancer cells. The antigen binds to a specific protein present only in the prostate cancer cell — then just sits there.
The research team used a super computer to create models of the molecules in computational chemistry. Then, these molecules were manufactured in the lab and tested on tissue cultures. Soon, the team hopes to begin testing on animals.
The antigen acts as what Helquist calls a "biological scaffold," and could lead to earlier cancer detection or prevent existing cancerous cells from spreading to other parts of the body.
The group is also looking into ways in which the antigen could serve as a target for cancer drugs, localizing treatment and minimizing damage to healthy parts of the body.
"One of the problems with conventional cancer treatment is that the drugs involved are very toxic. The drugs are not selective — they affect cancer cells and normal cells," Helquist said. "One can use these molecules to deliver a drug specifically to the site of cancer."
This antigen is just one of many compounds the Drug Design Group is investigating. Researchers also comb scientific journals in search of newly discovered compounds that may affect cancer. If one of the compounds appears promising, Notre Dame researchers may take it on as a project.
For example, Richard Taylor, a chemistry and biochemistry professor, is working with a compound that is capable of inducing apoptosis — programmed cell death — in cancer cells. The compound may eventually be converted into a drug capable of uprooting cancer growths.
Drug development is a slow process, however. It takes on average 12 to 15 years for the evolution of new drugs, according to Helquist.
A cellular approach
Across campus, researchers in the cell biology group are using cell cultures to look at movement of cancer cells.
According to Crislyn D'Souza-Schorey, a Walther Cancer Institute assistant professor, the team is studying how cells detach from a tumor and spread. The group is also looking at how cellular movement is regulated.
"We're looking at not just the invasive process but also what leads to it," D'Souza-Schorey said.
It's all in the genes
Meanwhile, researchers from the transgene group are taking a genetic perspective, studying how removing, changing or adding genes to a mouse chromosome will affect cancer.
The group is especially interested in genes involving blood clotting and anticoagulation because of their association with cancer.
"We want to find out what genes are up regulated or down regulated when you proceed from a benign state to a cancer state," Castellino said.
Approximately 50 people work in the transgene group — including a support staff of veterinary technicians and animal surgeons who watch over the Center's 5,000 experimental mice. The group conducts experiments with the special transgenic mice and detects the effects of gene alterations using $600 chips. An average experiment requires six different animals and 18 chips, according to Castellino.
Looking toward the future
In total, the Center has over $3 million in grants from the Department of Defense to work with over the next four years, in addition to grants from other sources and funding from the Institute and University. This funding, along with a talented faculty and appropriate resources, places the organization in an excellent position for basic cancer research in the future, according to Navari.
"The big advances in cancer [research] in the next five years are going to come from the laboratory," the researcher and practicing oncologist said.
All News Stories for Friday, February 15, 2002
