September 5, 2003

Browning receives VICC’s first Discovery Grant for viral cancer research

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Dr. Philip J. Browning looks at a gel with Grant Westlake, a research assistant in his lab. Browning is the first recipient of the Alan Rittenberg Discovery Grant for Cancer Research. Dana Johnson.

Browning receives VICC’s first Discovery Grant for viral cancer research

Initial funding from the Vanderbilt-Ingram Cancer Center’s first endowed “Discovery Grant” has been awarded to Dr. Philip J. Browning to support his research into the viral etiology of cancer.

The $35,000 award comes from the Alan Rittenberg Discovery Grant for Cancer Research, newly endowed with a $500,000 gift from the estate of Elsie Weinman Rittenberg in memory of Mrs. Rittenberg’s late son.

The funds will be used to support Browning’s research into the role of Kaposi’s sarcoma-associated herpes virus (KSHV) in the development of malignancies in immune compromised individuals. KSHV is linked to two common tumors among individuals infected with HIV, primary effusion lymphoma and Kaposi’s sarcoma.

“The virus encodes for proteins that block maturation of infected cells and promote unregulated cell growth,” said Browning, associate professor of Medicine, Cell & Developmental Biology and Cancer Research. “We believe this is a key event in the formation of these cancers.”

The funding will be used to study how viruses cause cancer.

“Our ultimate goal is to use our basic research to identify and develop novel targets for therapy that specifically target pathways that KSHV uses to cause cancer,” Browning said.

The HIV-KSHV-cancer connection is complex. HIV damages the immune system, which then sets the stage for KSHV to trigger tumor formation. (Both are sexually transmitted, so the risk factors are similar and co-infection is not unusual). Underlying this relationship is probably an individual’s genetic makeup that also plays an enabling role in cancer formation and progression, Browning said.

KSHV encodes a protein called K-cyclin. Cyclin proteins have broad functions related to cell growth control. In KSHV-infected cells, K-cyclin appears to contribute to increased expression of a gene called ID1. A recent study showed the ID1 inhibits the expression of thrombospin-1, an inhibitor of new blood vessel formation or angiogenesis. Angiogenesis is a hallmark of many cancers including KS.

“It is not clear how K-cyclin and another KSHV-encoded gene inhibit ID1, but understanding this mechanism could help elucidate how KSHV causes cancer,” Browning said.

The VICC Discovery Grant program, like that of the medical center, supports innovative work with potential to lead to new discoveries that can then attract funding from other sources. Browning said funding to explore novel ideas is critical to moving science forward.

“Although this work is a logical extension of what we’ve been doing in our lab, no one so far has made and explored this link,” he said. “Gene profiling of KSHV-associated tumors and improved animal models are crucial to better understanding how this all happens. That, in turn, opens other doors.”

KSHV is also present in tumors among patients who are not HIV-infected, Browning said. The study of this and other infectious agents related to cancer is important because as many as 30 percent of cancers worldwide have an infectious etiology, he said.

Among other infection-related cancers: Gastric cancers (helicobacter pylori); cervical/other genital cancers as well as oral-pharyngeal cancers (Human Papilloma virus); adult T-cell leukemia/lymphoma and hairy cell leukemia (HTLVI and HTLVII); liver cancers (hepatitis B and C); and non-Hodgkin’s and Hodgkin’s lymphoma (Epstein-Barr virus). HIV infection increases the risk for other cancers such as non-Hodgkin’s and Hodgkin’s lymphoma, multiple myeloma, gliomas and seminomas. Many of these tumors have a viral etiology.

“We need to understand not only how to vaccinate against these viruses, Browning said, “but in those individuals infected with these viruses, develop targeted antiviral therapies that may inhibit the growth of viral-infected tumor cells.”

Future Rittenberg Discovery Grants will be awarded as income is generated from the endowment.

Alan Rittenberg, who died in 1989, was a scientist at the Ernest Orlando Lawrence Berkeley National Laboratory in Berkeley, Calif. His mother, widow of Harold Rittenberg, died in Nashville in 2001 at the age of 91.

“Elsie wanted to establish a living memorial to her son, who was a scientist and a thinker,” said family friend Alan Saturn, executor of the Rittenberg estate. “I think this award is a fitting tribute to his life. I can think of no better way to fulfill Elsie’s wishes than to establish this endowment which will provide seed funds to jump-start exciting science.” Saturn’s wife, Nancy, is a member of the Vanderbilt-Ingram Cancer Center’s Board of Overseers and a cancer survivor.

Dr. Harold Moses, Vanderbilt-Ingram’s director and B.F. Byrd Professor of Oncology, said he hoped this endowment would be a model for future Discovery Grants. “We are grateful to the Rittenberg family and to Alan Saturn for his role in setting this wonderful example,” Moses said.

In recognition of the gift, Vanderbilt-Ingram has named the Alan Rittenberg Board Room, located on the 8th floor of the Frances Williams Preston Building.