Section: Rotations

Andre Van Wijnen, Ph.D.

Academic Role: Associate Professor

Faculty Appointment(s) In:
   Cell Biology

Runt-related transcription factors.

Runt-related transcription factors are an exciting class of proteins that contain a highly conserved DNA binding module, the runt domain, which has been evolutionarily conserved in most if not all animal species. These factors are key regulators of hematopoiesis (RUNX1/AML1), osteogenesis (RUNX2/CBFA1) and gastro-intestinal development (RUNX3/PEBP2aC). RUNX proteins are components of gene regulatory master-switches that regulate transcription of groups of genes required for the formation of hematopoietic cells, mature osteoblasts or other specialized tissues. Defects in the RUNX2/AML1 gene [e.g., t(8;21) chromosomal translocation] cause leukemia. Mutation of the RUNX2/CBFA1 gene causes cranio-facial abnormalities, supernumerary teeth and/or absence of clavicles [e.g., Cleido-Cranial Dysplasia]. One major goal of our studies is to map the gene regulatory pathways by which RUNX proteins determine lineage commitment, proliferative expansion and maturation of hematopoietic and osseous cells.

Potential Rotation Projects

Project #1: Analysis of the function of RUNX2 proteins in regulating osteoblast cell growth and differentiation. RUNX2 may regulate genes that are required for the expansion of osteo-progenitor cells, which has immediate implications for skeletal development, wound healing and tissue-engineering. The student will perform experiments focused on the identification and functional characterization of target genes of RUNX2. This project will use gene profiling techniques (e.g., Affymetrix gene micro-arrays) and stable cell lines conditionally expressing RUNX2 proteins.

Project #2: Transcriptional and post-transcriptional regulation of RUNX2 activity in response to osteogenic signals. The activity of RUNX2 is regulated by physiological mediators of skeletal development and bone cell differentiation (e.g., BMP2, TGFbeta, Vitamin D, glucocorticoids, FGF). The student will perform experiments aimed at understanding how regulatory signals are integrated at the RUNX2 promoter, or its mRNA or protein, to control the biological activity of RUNX2. Techniques include ligation-mediated PCR of genomic protein/DNA interactions, transient transfections of bone cells, and/or metabolic labeling studies.

Office: S3-326
Phone: 508-856-5942
E-mail: Andre.VanWijnen@umassmed.edu
Keywords: Signal Transduction, Developmental Biology

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