James Coghill, MD, has received a grant of more than $529,000 from the National Heart, Lung and Blood Institute (part of the National Institutes of Health) to study a promising target for new therapies to combat graft versus host disease, a serious complication of treatment for many blood cancers.
The Mentored Clinical Scientist Development Award (K08) is to support the career development of outstanding clinician research scientists. Dr. Coghill is an assistant professor of medicine in the division of hematology/oncology and a member of UNC Lineberger Comprehensive Cancer Center. For this work, Dr. Coghill will collaborate closely with his primary research mentors, Drs. Jonathan Serody and Stephen Frye.
A medical procedure called allogeneic hematopoietic cell transplantation, commonly known as a bone marrow or stem cell transplant, is the only known curative option for many patients with life-threatening blood cancers such as leukemia and lymphoma. Bone marrow stem cells reside within bones, and form all of the body’s blood cells including the white cells that mount immune responses to ‘foreign’ invaders. In a bone marrow transplant, stem cells are collected from a volunteer donor, and then administered to a patient following a large dose of chemotherapy or irradiation. While doctors are able to closely match donor and recipient tissues in most bone marrow transplants, a “perfect” match can only be achieved between identical twins. According to the national marrow donor program, the number of transplants performed in the United States doubled between 2005 and 2010 to more than 5200 a year.
In GVHD, genetic differences between the donor and recipient cause the donor immune cells to recognize certain recipient tissues as “foreign”, and to attack the transplant patient’s body. Symptoms can affect patient quality of life, and range from dry eyes and dry mouth, hair loss and skin rashes to hepatitis and lung and digestive tract disorders.
Dr. Coghill studies a receptor called CC-Chemokine receptor 7 (CCR7), which plays a role in the immune response that is at the root of GVHD. His laboratory studies show that cells lacking CCR7 maintain the desired anti-cancer immune effects after a transplant without displaying many of the characteristics that lead to GVHD. This new grant will allow his laboratory to examine over 120,000 compounds for agents that are able to block CCR7 function in laboratory-grown cells and in mouse bone marrow transplant models. Ultimately one or more of these compounds might be developed into drugs to prevent GVHD in human patients.