Blair B. Madison, Ph.D.

Assistant Professor
Internal Medicine
Gastroenterology

Developmental, Regenerative and Stem Cell Biology Program
Molecular Cell Biology Program
Molecular Genetics and Genomics Program

  • 314-362-9050

  • 8124

  • bmadison@dom.wustl.edu

  • https://madisonlab.wustl.edu/

  • Utilize functional genomics to identify new genes and pathways that regulate epithelial transformation in the intestine

Research Abstract:

The overarching goal of my research is to fully exploit new technologies (CRISPR/Cas and the Piggybac transposon) for studying how microRNAs (and their repressed targets) regulate intestinal stem cell dynamics and epithelial transformation/tumorigenesis. With nearly 2000 miRNAs documented in the human genome, the function of the vast majority of these small RNAs is largely unknown. Much of our recent work has focused on the Let-7 family of microRNAs (miRNAs) which are key regulators of developmental timing and are critical for repressing growth and maintaining cellular differentiation. Using protocols and technologies we have developed, we are exploring the role of Let-7 and other miRNAs in the gut using both organoid and mouse models (GEMMs). Organoids, which are ex vivo primary cultures of human intestinal epithelium in 3D scaffolds, have become a powerful platform for studying stem cell biology and epithelial transformation. Using GEMMs and organoids, we want to answer the following questions regarding miRNAs and their targets. How are stem cells established in the gut? What regulates their replenishment when they are lost due to tissue damage? How do early mutations affect stem cell dynamics in the crypt? Which miRNAs regulate stem cell development/specification, fate, and recruitment following dedifferentiation?

Selected Publications:

Zacharias WJ*, Madison BB*, Kretovich KE, Walton KD, Richards N, Udager AM, Li X, Gumucio DL. Hedgehog signaling controls homeostasis of adult intestinal smooth muscle. Dev Biol. 2011 Jul 1;355(1):152-62. *Authors contributed equally. COVER IMAGE. Cited by Faculty of 1000.

Madison BB, Liu Q, Zhong X, Hahn CM, Lin N, Emmett M, Stanger BZ, Lee JS, Rustgi AK. LIN28B regulates growth and tumorigenesis of the intestinal epithelium via Let-7. Genes and Development. 15 October 2013; Vol. 27, No. 20.

Madison BB, Jeganathan A, Mizuno R, Winslow MM, Castells A, Cuatrecasas M, Rustgi AK, Let-7 Represses Carcinogenesis and a Stem Cell Phenotype in the Intestine via Regulation of Hmga2. PLoS Genetics, 2015 Aug 5;11(8).

Wen Y, Liao G, Pritchard T, Zhao TT, Connelly JP, Pruett-Miller SM, Blanc V, Davidson NO, Madison BB. A stable but reversible integrated surrogate reporter for assaying CRISPR/Cas9-stimulated homology-directed repair. J. Biol Chem. 2017. J Biol Chem. 2017 Apr 14;292(15):6148-6162.

Strubberg AS, Veronese-Paniagua DA, Zhao T, Dublin L, Pritchard T, Bayguinov P, Fitzpatrick JA, Madison BB. The Zinc Finger Transcription Factor PLAGL2 Enhances Stem Cell Fate and Activates Expression of ASCL2 in Intestinal Epithelial Cells. Stem Cell Reports 2018 2018 Aug 14;11(2):410-424.

Last Updated: 8/21/2018 9:38:40 AM

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