A new research alliance focuses on a molecular master switch suspected of igniting the inflammatory immune response that drives asthma and other allergic diseases.
The University of Texas M. D. Anderson Cancer Center and Baylor College of Medicine have launched the Texas Medical Center Asthma and Allergic Diseases Cooperative Research Center, funded by a $5.6 million five-year grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
"We can manage asthma, but there is no cure. Finding the cause of asthma is a fundamental question in immunology," said principal investigator Yong Jun Liu, M.D., Ph.D., professor and chair of the Department of Immunology at M. D. Anderson. "The molecule we are studying, known as TSLP, appears to represent a very, very early trigger between allergens that find their way into the lungs and asthma."
"This program is focused on trying to delineate the mechanisms by which viruses and allergens are able to initiate and drive the allergic response and progression of asthma," said Dr. David Huston, professor of immunology at BCM, director of the college's Biology of Inflammation Center, and co-principal investigator. "It's probably the hottest area right now in the study of allergic diseases."
The incidence and severity of asthma, a debilitating and potentially life- threatening constriction and inflammation of the airways, has increased over the past 20 years, with more than 155 million people affected in developed countries alone.
Earlier research by Liu established that inhalation of allergens, such as pollen or viruses, sets off production of TSLP in the lining of the lungs (epithelial cells) and by specialized cells known as mast cells. TSLP then launches a molecular cascade that results in overproduction of the immune system T cell known as Th2, a known culprit in the inflammation that causes chronic asthma.
"Th2 is an important, heavily studied T cell that causes asthma," Liu said. "Our question is what induces and maintains Th2?"
By nailing down the details of this process, the investigators expect to generate new therapeutic targets for allergic disease and asthma. Liu expects drug development to begin late in the five-year grant period and extend beyond that.
The program is divided into four research efforts, starting with a project led by Huston that examines the mechanisms of TSLP expression by the epithelial and mast cells in human lungs.
Project two focuses on how TSLP then activates dendritic cells, key players in the immune system that engulf intruding antigens and present key portions of the intruder to T cells (Th2), which in turn help generate an antibody response. Li-yuan Yu-lee, Ph.D., professor of medicine at BCM, leads this project, on which Margie Moczygemba, Ph.D., assistant professor of medicine at BCM is co-investigator.
Project three, led by Liu, examines how the TSLP-generated dendritic cells in turn propagate Th2 effector and memory cells.
Project 4, led by Chen Dong, Ph.D., associate professor of immunology at M. D. Anderson, examines how inflammatory T helper cells then upregulate TSLP, perpetuating the inflammatory cycle.
Huston heads the project's clinical research core, which includes Drs. Nick Hanania, Robert Atmar, Pedro Piedra, and Robert Couch, at BCM. Liu leads the analytical and administrative cores. All four research projects also will require close interaction, Liu said.
Steve Ziegler, Ph.D., director of the Immunology Program at the Benaroya Research Institute at Virginia Mason in Seattle, is co-investigator on projects 1 and 2. Ziegler is an expert on using mouse models to understand the biology of TSLP.
Immunological research at M. D. Anderson focuses on priming the immune system to identify and attack cancer cells. Inflammation also is involved in cancer development and growth, Liu said.
"In some cancers, the microenvironment that the tumor creates around itself looks like an allergic type of inflammation," Liu said. "We need to understand this type of inflammation so we can design ways to block it in the tumor microenvironment, because it promotes tumor growth.
"While M. D. Anderson's focus is not on allergies and asthma, Dr. Huston is one of the best physicians in the country for allergic disease and has a strong research program," said Liu. "Our teams are complementary to each other's expertise. This is an exciting cooperative program and both institutions will gain from this collaboration."
In addition to several shared clinical and cancer-related research projects, this is the second major research collaboration established between M. D. Anderson and Baylor College of Medicine to study a disease other than cancer. In 2002, the two institutions formed the Bone Disease Program of Texas, which focuses on the study of osteoporosis and the treatment of bone disease.
The two institutions launched a joint neurosurgery program in June 2005, with Dr. Raymond Sawaya, M.D., chair of the of M. D. Anderson Neurosurgery Department for 15 years, also appointed chair of the Baylor College of Medicine Department.