Veterinary cancer collaboration

Columbus, Ohio

- A decade of research and $20 million in grants yields an impressive recipe for uncovering new information about retrovirus-associated cancer as it affects both animals and humans.

Dr. Michael Lairmore

The Ohio State University (OSU) College of Veterinary Medicine announced in July that a team of its researchers working in the school's Center for Retrovirus Research have, along with human medicine collaborators from OSU's Comprehensive Cancer Center (CCC), earned for the second time a competitive research grant from the National Cancer Institute.

The grant, worth $10.9 million over five years, was awarded to the university by the National Cancer Institute and will allow researchers from OSU's veterinary college to continue its studies of retroviruses. Examples of retroviruses include equine infectious anemia in animals and T-cell leukemia and lymphoma in humans.

The first grant, worth $8.9 million, was awarded to the university in 2003 for studies investigating how some retroviruses cause white blood cells, or lymphocytes, to change into cancer.

The continuation of the study includes five interactive projects and three administrative cores, according to principal investigator Michael Lairmore, DVM, Ph.D. Lairmore also is professor and chair of the department of veterinary biosciences at OSU, associate director for basic research at the CCC and is a member of the CCC's Viral Oncogenesis Program.

The way the study is being conducted is a great example of a new trend of tying together human and animal medicine, Lairmore says.

"We have MDs; we have PhDs and DVMs and DVM PhDs that are involved in this project, so you really cover the gamut of degrees involved in this research," Lairmore says, adding the collaborative atmosphere of the study is closely linked to the One Health Initiative started last year by the American Veterinary Medical Association and the American Medical Association. "We do exemplify the same theme. There's lots of overlap, lots of efforts to study both human and animals."

Conducting studies in unison allows both animal and human medical researchers to gain a broader understanding of how viruses and other afflictions operate, he says. For example, Lairmore says retroviruses were discovered in animals long before they were discovered in humans, and many viruses that cross species belong to the same group, like the bovine leukemia virus and human immunodeficiency viruses.

The key to this research is to find common ways these viruses act in each species, Lairmore says.

• Project 1 will be led by Lairmore and investigate the role of novel accessory proteins of human T-lymphotropic virus type 1 (HTLV-1), the first described human retrovirus which causes an aggressive form of lymphoma and leukemia as well as other immune system disorders. The long-term goal of the project is to understand the role of certain proteins - p121, p30ll and Rex in the establishment of HTLV-1 infection in vivo.

• Project 2 will study how Rex, a viral regulatory protein, regulates viral gene expression and contributes to the overall biology of the HTLV. The project will be led by Dr. Patrick Green, PhD, of OSU. According to the college, about 15 million to 25 million people around the world are affected with two separate HTLV strains, which are associated with leukemia and neurological disease in some patients. Even though an infected patient develops an antibody, the virus manages to stay with those affected throughout his/her life. Green's group will try to develop an HTLV that replicates independent of Rex to directly assess the role it plays in cellular transformation.

• Led by Dr. Kathleen Boris-Lawrie, PhD., Project 3 will take a look at the mechanisms of retrovirus-host cell translational enhancement. The project will test post-transcriptional control of retrovirus cell interaction through the use of novel control elements and retroviral vectors, OSU reports. The hope is that the group will provide information that will aid in the engineering of enhanced retroviral vector systems for gene transfer applications.

• Project 4 will evaluate molecular determinants of hormonal-induced hypercalcemia, a complication of viral-associated cancer, according to the university. Led by Dr. Thomas Rosol, former OSU veterinary college dean, Project 4 seeks to understand the regulation and roles of parathyroid hormone-related protein in the development of T-cell malignancy and cancer-associated hypercalcemia in humans with adult T-cell lymphoma/leukemia.

• Project 5, led by Lee Ratner, MD, and Katherine Weilbaecher, MD, of Washington University, will look into the role of tax, a regulatory protein, in lymphocyte proliferation and virus-associated disease in a transgenic mouse cancer model. The goal is to examine nuclear factor kappa B inhibitors as a form of cancer treatment, OSU says.