Sonia H. Pearson-White, PhD

    Associate Professor of Microbiology

Genetic regulation of growth and differentiation

Stem cells pass through a decision point with every cell cycle -- whether to divide or differentiate down a particular lineage. To gain insight into cancer and embryonic development we must understand the genetic regulation of this growth/differentiation decision point. Currently we focus on the Ski and Sno proto-oncogenes, which have the unique property that they can promote both oncogenic transformation and terminal skeletal muscle differentiation. Ski and Sno encode homologous cell cycle-regulated nuclear proteins that are widely expressed and function as transcriptional co-repressors as part of protein complexes with Rb, Sin3A, and histone deacetylase (HDAC). Furthermore, Ski and Sno interact directly with the TGF-ß effector proteins SMAD 2, 3 and 4 in a TGF-ß-dependent manner, repressing SMAD trans-activation of target genes. Thus, Ski and Sno participate in the governance of the TGF-ß signaling pathways, which regulate cellular proliferation, differentiation, and apoptosis. We hypothesize that Sno and Ski interact with these proteins to modulate the growth and differentiation of multiple cell types, including regenerating skeletal muscle and T cells undergoing activation. Our recent results provide strong evidence that Sno is a significant negative regulator of anti-proliferative TGF-ß signaling in both T cells and other cell types in vivo. Ongoing studies use molecular biology, experiments in tissue culture cells, and genetic manipulations in mice.

Representative Recent Publications

  1. Pearson-White, S. and R. Crittenden, "Proto-oncogene sno expression, alternative isoforms, and immediate early serum response," Nucleic Acids Research, 25:2930-2937, 1997.
  2. Pearson-White, S., "Genotyping DMDmdx3Cv and DMDmdx4Cv mutations in mice using PCR", Neuromuscular Disorders, 12:366-370 (2002).
  3. Lijun Xia, Markus Sperandio, Tadayuki Yago, Michael McDaniel, Richard D. Cummings, Sonia Pearson-White, Klaus Ley, and Rodger P. McEver, "Neutrophils from P-selectin Glycoprotein Ligand-1-deficient Mice Roll Weakly on P-selectin and Tether Poorly to E-selectin in Flow", J. Clinical Investigation 109:939-950 (2002).
  4. Pearson-White, S., and McDuffie, M., "Defective T Cell Activation is Associated with Augmented TGF-beta Sensitivity In Mice With Mutations In The Sno Gene", submitted 2003.
  5. Pearson-White, S., and Colmenares, Clemencia, "Ski/Sno double mutant embryos are developmentally arrested early in embryogenesis," in preparation.

Some Links

For more information email sp3i@virginia.edu.