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Dr. Mary Carrington: The Management of Science

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"Having a full plate" aptly describes Dr. Mary Carrington's life. Dr. Carrington is an SAIC-Frederick, Inc. Principal Investigator (PI) within the Laboratory of Genomic Diversity and serves as Director of SAIC-Frederick's Basic Science Directorate. The Basic Science Directorate is divided into two programs-the Basic Research Program (BRP), which Dr. Carrington oversees and the AIDS Vaccine Program (AVP) headed by Dr. Jeffrey Lifson.

  According to Dr. Carrington, it has been a challenge to juggle both roles, but also a worthwhile, positive experience for her. Dr. Carrington, who became Director in 2002, oversees the BRP, which currently includes approximately 200 scientific professionals ranging from PIs to technicians, all of whom work in support of NCI's mission to prevent and successfully treat cancer and infectious diseases related to cancer. Unlike SAIC's other programs, there are approximately 15 PIs within the BRP and, like their NCI counterparts, these SAIC researchers conduct independent research and are reviewed during each lab's site visit. Dr. Carrington's responsibilities include providing scientific oversight for the BRP, serving as a liaison between the BRP and SAIC senior management, and evaluating the progress of all the SAIC investigators. Dr. Carrington also consults with BRP staff on career development, scientific discoveries and any other work-related issue. "I am basically available to anyone who walks in my door to discuss anything regarding their work," says Dr. Carrington. Juggling her management role and her research has been a bit of a balancing act. "It has been a challenge to take on major, new responsibilities and maintain the same level of scientific productivity that I had before accepting this position, but overall, I think it has taught me how to make better use of my time," replies Dr. Carrington. "Also, it is often refreshing and interesting to break my day up between two different types of job duties." Dr. Carrington added that she's learned a lot more about what the other SAIC PIs are doing than she previously knew, "which is a good thing."   Dr. Carrington really enjoys learning about the research her fellow PIs are conducting; this has even led to some new collaborations.

HLA Class I:   There Is Strength in Diversity

In her scientific role, Dr. Carrington directs research focusing on the human major histocompatibility complex (MHC).   The MHC (found on chromosome 6) is the most gene-dense region of the human genome and approximately 40% of the genes found in this region are involved in the immune response.   She has been concentrating on the class I genes, HLA-A, -B, and -C, which are involved in both innate and acquired immunity.   When a cell is infected by a virus, viral proteins are chewed up [by the cell] and depending on what HLA types someone has, different peptides will be taken up and presented on that cell's surface, thus signaling to the immune system that the cell is infected and needs to be destroyed.   The HLA genes are extremely polymorphic (i.e., diverse), which means if you took samples from 100 unrelated people, for example, you would be unlikely to find any two individuals with an identical set.   This diversity, which has been generated over the course of our evolution, is important and beneficial on two levels-it protects us as individuals and as a species.   For example, if a new type of virus emerges, it might kill many people, but due to the sheer diversity of HLA types among humans, there would likely be some individuals who would have some protection.   HLA genes do not, however, account for all differences in immune responsiveness across individuals; many other genes are involved in resistance to viral infection, and other factors, such as variation in the virus and environmental factors, also contribute to an individual's ability to withstand infection. "The diversity of HLA is likely to be involved in determining the outcome to every single infectious agent we will ever encounter," says Dr. Carrington. "But the extent to which it determines that outcome is going to vary in quite a large way," she adds.

Dr. Carrington's lab uses human immunodeficiency virus (HIV) as a model for their studies.   There is good clinical data on the HIV cohorts she uses, and, because it is a fairly new disease, there has not been time for any strong natural selection to alter the frequency of any specific HLA types.   "That may be part of the reason why the effects of HLA on HIV have been more clear-cut than any other infectious disease," explains Dr. Carrington.   The effects of HLA on rate of progression after infection with HIV are apparent for some HLA types: some HLA types are associated with a rapid rate of progression, while others are associated with slow progression.

Dr. Carrington is also interested in the leukocyte receptor complex (LRC), a region that contains many genes, which encode molecules that are expressed on different types of leukocytes.   One set of genes, known as killer immunoglobulin-like receptors (KIR), are expressed on natural killer cells and on some cytotoxic T lymphocytes.   The KIR molecules help regulate the activity of natural killer cells, playing a role both in activation and inhibition of these important immune cells.   "We became interested in the KIR because their ligands on potential target cells are certain types of HLA class I," explains Dr. Carrington.   HLA class I works with KIR to initiate the killing of infected cells and tumor cells in an innate immune response; later on, as the infection progresses, class I molecules mediate the acquired immune response.   Dr. Carrington's lab is working towards developing a detailed picture of exactly how KIR functions during various disease processes from a genetic epidemiological approach.   Dr. Carrington hopes that, eventually, this research will lead to new therapeutics for human diseases such as AIDS.

Written by Sue Fox
Office of Communication
Center for Cancer Research (CCR)
National Cancer Institute at Frederick

Edited by:
Kathryn Ellis, Office of Communication, CCR
Maritta Grau, Scientific Publications, Graphics and Media
SAIC-Frederick, Inc.

Photography by Martha Welch
Scientific Publications, Graphics and Media
SAIC-Frederick, Inc.

Web Graphics and Development by Jim Miller
Computer and Statistical Services
National Cancer Institute at Frederick