Dr. Shannon Kenney
Receiving three federal grants from the National Institutes of Health (NIH) within a year is nearly unheard of in the research world, but not for Dr. Shannon Kenney who was awarded two grants from the National Cancer Institute (NCI) and a third from the National Institute of Allergy and Infectious Diseases (NIAID) within a calendar year! Dr. Eric Johannsen, another McArdlite, is a co-investigator on these grants.
Grants from the National Cancer Institute are especially difficult to obtain, and currently only around the top eight percent of grants are funded.
“It was a lot of hard work because I had to submit each one of them more than once to get them funded. I was very persistent,” she said.
Dr. Kenney balances her time between working as a basic science researcher and as an Infectious Diseases clinician. Her research focus is on Epstein-Barr Virus (EBV), and she finds balancing her two lines of work to be challenging but rewarding. Her clinical work continually motivates her to advance her research, and her research helps inform her work as a clinician.
EBV is a gamma herpesvirus that causes mononucleosis, often known as “mono” or “kissing disease” because the virus can spread through saliva. The virus is typically well controlled by our immune system.
But once a person is infected, the virus remains in the body forever. In fact, about 90% of the world is infected with the virus, but only about half of those infected will ever develop mononucleosis.
In order to replicate itself and spread throughout the body, the EBV virus hijacks a white blood cell type known as a B cell. In B cells, the virus enters the “latent” form of infection where it does not produce infectious particles or kill the cells. Nevertheless, EBV can express up to nine viral proteins during latent infection, and these EBV proteins can induce B cells to proliferate and potentially be transformed into malignant cells.
Typically, the immune system recognizes EBV-infected B cells expressing viral transforming proteins, and fights off the virus before it causes any malignancy. However, immunosuppressed individuals such as organ transplant patients and people living with HIV are at higher risk because their bodies do not recognize the virus as quickly, so the virus has time to produce B cell lymphomas.
“When we transform B cells in the lab in culture, we always get the type of infection where all nine proteins are made, and it’s fully transforming. We’ve spent a lot of time as a field understanding what each protein does and how it works, and we’ve learned a lot,” said Kenney.
Yet, even immunocompetent people infected with EBV can rarely develop EBV-associated cancers such as Hodgkin’s lymphoma that do not express all nine of the transforming proteins required to transform B cells in tissue culture. It is thought that the ability of Hodgkin lymphomas to stop expressing certain viral transforming proteins helps these tumors to evade the immune response.
According to Dr. Kenney, Hodgkin’s lymphoma mostly affects young people and is one of the most common EBV-associated cancers in the United States. About half of Hodgkin’s lymphoma cases contain EBV, and EBV infection is thought to play a role in causing these tumors.
Using the NCI grant that began last summer, Kenney and her team created a humanized mouse model to further study this mystery that could not be studied in cell culture.
“We think there is something about the humanized mouse model that provides a growth factor that allows that virus to transform B cells into Hodgkin-like lymphomas in a way it cannot do in tissue culture. We are trying to figure out exactly what these growth factors are.”
Kenney and her team are continuing their research to understand what is helping these lymphomas grow even when some of the essential viral proteins required for transformation of B cells in tissue culture are not expressed.
In addition to the work on EBV-positive Hodgkin’s lymphoma, Kenney studies EBV-associated Burkitt lymphoma. Burkitt lymphoma was the first ever human cancer discovered to be associated with a human virus, and has long been known to also be associated with malaria.
Yet the role of malaria plays in the development of Burkitt lymphoma is still largely unknown. In order to better answer this crucial question, Kenney and her team are collaborating with Rosemary Rochford at the University of Colorado.
Using the NCI grant that began this July, their work will include traveling to Kenya to measure levels of EBV in the blood of children with malaria who have a particular strain of EBV that the Kenney lab recently discovered to produce more infectious viral particles than other EBV strains. This strain is over-represented in EBV infected Burkitt lymphomas. Their hypothesis is that the cancer-associated virus allows B cells to produce large amounts of virus particles in children with malaria.
If their hypothesis is correct, it may provide an impetus for screening people in the malaria belt to for this cancer-associated EBV strain.
“I hope that we can identify a specific strain of EBV that predicts a higher risk level so that we can concentrate our efforts in terms of preventing cancer in that high-risk group,” Kenney said.
The third grant Dr. Kenney is working with from the NIAID is focused on the comparison of Type I and Type II of EBV. Type II EBV is most commonly found in the malaria belt of Africa, and has not been as extensively studied as Type I EBV. Dr. Kenney is studying how the viruses differ using the humanized mouse model as well as cell culture transformation models.
Dr. Kenney, who is also the co-leader of the UWCCC Virology program, states that “virally induced cancers (due to not only EBV, but other viruses such as HPV, HBV and HCV) account for approximately 15% of all human malignancies. Understanding how viruses cause human cancers offers new opportunities to prevent these malignancies using vaccines, or to develop new treatments for these cancers using drugs and/or immunotherapy targeted specifically against viral transforming proteins. I am grateful to the NIH for funding my research and hope that my dual training as an Infectious Diseases clinician and a basic virologist helps me to develop new insights into EBV-induced cancers that result in new therapies.”
By Dominique Barthel (firstname.lastname@example.org)