The Cell Pathology Laboratory studies intracellular signaling pathways in health and disease.
One long-standing area of emphasis is the high affinity IgE receptor, FceRI, of rodent and human mast cells and basophils. This heterotetrameric (aß?2) receptor belongs to the family of multi-chain immune system receptors that includes the T cell receptor, the B cell receptor and several of the Fc? receptors. All of these receptors share a common tyrosine-based activation motif, the ITAM. Cross-linking this receptor with multivalent antigen on mast cells stimulates a cascade of immediate biochemical, ionic and functional responses including: activation of cytoplasmic tyrosine kinases, phospholipase C (PLC) and phosphatidylinositol 3-kinase (PI 3-kinase); inositol 1,4,5-trisphosphate (IP3) synthesis; Ca2+ mobililization; Ras and MAP kinase activation; cytoskeletal remodeling; and upregulation of adhesion. Recent microarray studies in the lab have identified over 300 genes whose expression levels change within hours of FceRI crosslinking. More recent research also addresses signaling through the ErbB family of tyrosine kinase receptors implicated in cancer and explores signaling dysregulation in human childhood leukemia (pre-B ALL).
Our principal goals are to understand spatio-temporal and molecular mechanisms that facilitate cell signaling, particularly in cell membranes and in the regulation of intracellular calcium. We use high resolution electron microscopy to map receptors and their signaling partners on membranes and live cell confocal and TIRF imaging to follow receptor dynamics. These approaches are complemented by partnerships with Sandia National Lab colleagues to develop new microscopy probes and to image native membranes using atomic force microscopy. Active collaborations with UNM Math, Physics and CS faculty, as well as with the Sandia and Los Alamos National labs are aimed at developing mathematical models of signaling pathways (see STMC website).
The laboratory presently comprises three faculty, three senior fellows, four senior technical staff and two biomedical sciences graduate students. Several graduate students from the UNM Computer Sciences, Electrical and Computer Engineering and Mathematics and Statistics Depts are also affiliated with the lab. Lab funding is from the NIH (NIGMS, NIAID and NCI), from several SNL subcontracts and from the Leukemia/Lymphoma Society. Faculty effort in the laboratory is roughly divided into these areas: