News & Publications

Albany Medical College Researcher Receives $2.9 Million in NIH Grants

ALBANY, N.Y., November 26, 2007 - A scientist at Albany Medical College has received two grants totaling $2.9 million from the National Institutes of Health to further her studies into the role transcription factors may play in a wide variety of disease such as leukemia and autoimmune disorders like celiac disease, multiple sclerosis and rheumatoid arthritis.

Specifically, the 5-year grants will enable Dorina Avram, Ph.D., associate professor in the Center for Cell Biology and Cancer Research at the Albany Medical College, and her team of scientists to continue to study the role transcription factors play in various stages of lymphocyte (white blood cell) development. They will concentrate on BCL11B, a transcription factor that Dr. Avram herself discovered several years ago. It is hoped that achieving a better understanding of this and other transcription factors will ultimately lead to better treatments for these diseases.

Autoimmune diseases are the result of the body's inappropriate immune response to its own cells and tissues.  Similarly, leukemia is caused by an over-proliferation of immature white blood cells, which become dysfunctional and interfere with the normal function of other cells in the body.

Transcription factors, Dr. Avram explains, are the molecules that are critical for the development and function of the immune system. How lymphocytes mature and divide, as well as when and how they function in immune responses is all controlled by transcription factors. Understanding
how these responses are controlled may lead to a better understanding of both autoimmune diseases and leukemia.

A $1.9 million five-year grant will enable Dr. Avram to study the role of BCL11B in CD4+ T lymphocytes. According to Dr. Avram, these types of lymphocytes-or helper cells-are major players of the immune system, and act as the "middlemen" by secreting small proteins called cytokines. The cytokines function as signals to instruct other classes of immune cells to produce antibodies or to kill cells infected with viruses or other pathogens. Dr. Avram's laboratory has evidence that BCL11B plays a vital role in controlling the development and function of these lymphocytes. 

"In the absence of BCL11B, the number of CD4+ T lymphocytes is very small, and even that small number has an altered function and is unable to "help" the other types of immune cells," Dr. Avram explains. "What we want to understand now is how BCL11B controls development of CD4+ T lymphocytes by removing BCL11B at different stages of development. If we have a better understanding of how these cells are controlled by BCL11B, how they develop and how they mature, we can think about strategies to adjust the lymphocyte response and consequently the immune response." 

Dr. Avram adds that this research may also increase our understanding of leukemia, as studies have shown that BCL11B also controls immature T lymphocyte survival and proliferation, which are typically dysfunctional in T cell leukemias. "Removal of BCL11B in immature lymphocytes has been shown to cause lymphoma in mice," explains Dr. Avram. "We want to understand why this cellular transformation occurs."

A $1 million grant will enable Dr. Avram to study the role of BCL11B in another class of T lymphocytes-T-regulatory cells-which regulate the body's immune response by shutting down specific branches of the immune system after adequate response. Dr. Avram and her team have already found that when the transcription factor BCL11B was removed from the T-reg cells in mouse models, the mice developed inflammatory bowel disease-evidence of an uncontrolled overactive immune system. 

In addition, the funding will allow the group to investigate another T lymphocyte lineage-natural killer T cells- special types of lymphocytes which when activated produce cytokines and also release cell killing molecules.  Studies have suggested that these cells seem to have altered function in the absence of BCL11B. 

"So now that we know this, we want to figure out what exactly is altered in these cells. T-regulatory and natural killer T cells are fairly newly-discovered cells, and their developmental program is not very well understood," says Dr. Avram. "Overall these studies will enhance our understanding of the transcriptional control of late stages of T-cell development, transcriptional control of helper, regulatory and natural killer T cells, and will have important implications for autoimmune diseases that will help us identify interventional strategies." 

Dr. Avram's team includes postdoctoral fellow Diana Albu, Ph.D., graduate students Mike Rozell, Debarati Bhatakaria and Evi Loghin, and technical assistants Donguyn Feng, Danielle Califano and Rui Ou.

Albany Medical Center is northeastern New York's only academic health sciences center. It consists of Albany Medical College, Albany Medical Center Hospital and the Albany Medical Center Foundation, Inc. Additional information about Albany Medical Center can be found at www.amc.edu.