Scholar Profile

Cornelis Murre

University of California, San Diego
Voice: 858-534-8796
Fax: 858-534-7108
Personal Homepage
1991 Searle Scholar

Research Interests

Transcription Factors Regulating Lymphoid Differentiation

The overall objective of our research is to understand the molecular mechanisms that drive immunologic processes and malignancies. It has become clear that the events that control lymphoid differentiation are a result of changing patterns of gene expression. The studies in my laboratory are focused on a class of transcription factors, helix-loop-helix (HLH) proteins, that are in part responsible for the alterations in gene expression during B cell development. One particular class of HLH protein is the E-proteins, that include E12, E47, E2-2, and HEB. E12 and E 47 are encoded by one gene, E2A, and arise through differential splicing. E2-2 and HEB are encoded by different genes. Differentiation of B cells in E2A mutant mice is blocked at a stage prior to immunoglobulin gene rearrangement. These data suggested that E2A is a central regulator in early B cell development. We are now further dissecting the contributions of E2A and other E-proteins in lymphoid differentiation, and we are determining the hierarchy of transcription factors that control lymphoid development.

In addition to their role in lymphoid development, the E2A gene is a key factor in generating pediatric leukemias. Specifically, in pre-B ALL, the E2A HLH domain has been replaced with the homeodomain of PbX1, normally a gene product involved in morphogenesis. We have recently identified a target gene of E2A/Pbx1, encoding a novel member of the FGF growth factor family, designated FGF-10. FGF-10 is normally expressed in the retina and midbrain and is inappropriately induced by E2A/Pbx1. We are now examining the mechanism of how E2A/Pbx1 and FGF like growth factor contribute to B cell malignancies.