Michael Croft, Ph.D., and his team focus on a number of protein molecules that are members of the tumor necrosis factor (TNF) and tumor necrosis factor receptor (TNFR) family, a group of proteins believed to play important roles in the ability of the immune system to guard the body against harmful microorganisms. The TNFR molecules studied by Dr. Croft and his laboratory are expressed on T lymphocytes and other cells of the immune system and emerging evidence is suggesting they are crucial for the effective function of these cells in many types of immune response.
Membrane-expressed receptors termed costimulatory molecules have long been known to be essential for T cell responses. These molecules fall into two main groups, namely Ig superfamily members, and TNFR superfamily members. There are many TNFR family members that control T cell activity, including the molecules that are the current focus of the Croft lab, namely OX40 (CD134), 4-1BB (CD137), HVEM (CD270) and LTβR, in addition to others such as TNFR2, DR3, CD30, GITR, and CD27. These TNFR family proteins can exert direct activities, with the receptors being constitutively (HVEM, CD27) or inducibly (OX40, GITR, 4-1BB, CD30, TNFR2) expressed on T cells, and available to be ligated by their soluble TNF ligands, or by the membrane expressed versions that can be presented on APC or other cells. Understanding how these molecules function is likely key to understanding how immune disease and inflammation are controlled and how immune responses to infectious pathogens can be generated.
Currently, four drugs have been approved for clinical use that target molecules in the TNF and TNFR protein families. Dr. Croft's laboratory is investigating the roles of other related molecules in several diseases, including asthma, multiple sclerosis, and diabetes, to determine if they could be targets for therapeutic intervention to suppress disease symptoms. Another line of research is investigating whether substances that can signal T cells and other immune cells through TNFR family proteins can be used to increase natural immune responses. This is particularly important for vaccination against viruses and diseases such as cancer, in which T cells do not function strongly enough or fast enough to combat the growth of the virus or growth of the tumor cells.
News & Events
BREAKTHROUGH: Role of LIGHT molecule for remodeling in the lung
Michael Croft, Ph.D., has discovered a molecule’s previously unknown role as a major trigger for airway remodeling, which impairs lung function, making the molecule a promising therapeutic target for chronic asthma, chronic obstructive pulmonary disease (COPD) and several other lung conditions. A scientific paper on Dr. Croft’s finding was published online in the prestigious journal, Nature Medicine.
BREAKTHROUGH: OX40 Ligand in Asthma
A major asthma discovery by a researcher at the La Jolla Institute for Allergy & Immunology has been licensed by MedImmune, a leading innovation-focused biotechnology company and wholly owned subsidiary of AstraZeneca PLC. MedImmune licensed the discovery to explore its use in the development of a potential biologics drug for treating asthma. Under the agreement, MedImmune was granted exclusive intellectual property rights to the discovery, which demonstrated the pivotal role of a protein called the OX40 ligand in asthma. The finding was made by the laboratory of La Jolla Institute scientist Michael Croft, Ph.D., and marked a major milestone in asthma research.