If the intestinal epithelium was unraveled it would be a one-cell-thick layer with enough surface area to cover a tennis court. This thin layer selectively absorbs nutrients while repelling toxins and pathogens. Because it’s a dirty job, the entire epithelium is shed and replenished continuously (much like our skin) with the entire epithelium replaced every few days. High exposure to noxious substances coupled with high rates of proliferation make this epithelial layer susceptible to both cancer and inflammatory disease. Intestinal diseases are among the most prevalent maladies in our society.
Our group investigates how transcription factors, co-regulators, and specific chromatin structures are assembled into enhanceosomes, multiprotein complexes that control gene expression over distances of many kilobases. These complexes are scattered throughout our genomes, selectively reading the genetic code and the epigenetic landscape to allow the cell to integrate external stimuli and respond with genomic output. Different combinations of transcription factors, co-regulators, and chromatin modifications can respond uniquely to cellular states and our goal is to understand the rules via which these complexes operate. We discover these processes in the healthy intestinal epithelium and then dissect each component part using mouse genetics. We then compare how these processes are disrupted in intestinal disease with the goal of unraveling the causes and discovering the cures for intestinal health.
Verzi MP, Shin H, San Roman AK, Liu XS, Shivdasani RA. Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding. Mol Cell Biol. 2012 Nov 5.
Beuling E, Aronson BE, Tran LM, Stapleton KA, ter Horst EN, Vissers LA, Verzi MP, Krasinski SD. GATA6 is required for proliferation, migration, secretory cell maturation, and gene expression in the mature mouse colon. Mol Cell Biol. 2012 Sep;32(17):3392-402.
Verzi MP, Shin H, Ho LL, Liu XS, Shivdasani RA. Essential and redundant functions of caudal family proteins in activating adult intestinal genes. Mol Cell Biol. 2011 May;31(10):2026-39.
Verzi MP, Shin H, He HH,Sulahian R, Meyer CA, Montgomery RK, Fleet JC, Brown M, Liu XS, Shivdasani RA. Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2. Dev Cell. 2010 Nov 16;19(5):713-26.
Verzi MP, Shivdasani RA. Stem cells: The intestinal-crypt casino. Nature. 2010 Oct 28;467(7319):1055-6.
Verzi MP, Hatzis P, Sulahian R, Philips J, Schuijers J, Shin H, Freed E, Lynch JP, Dang DT, Brown M, Clevers H, Liu XS, Shivdasani RA. TCF4 and CDX2, major transcription factors for intestinal function, converge on the same cis-regulatory regions. Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15157-62.
Pomerantz MM, Ahmadiyeh N, Jia L, Herman P, Verzi MP, Doddapaneni H, Beckwith CA, Chan JA, Hills A, Davis M, Yao K, Kehoe SM, Lenz HJ, Haiman CA, Yan C, Henderson BE, Frenkel B, Barretina J, Bass A, Tabernero J, Baselga J, Regan MM, Manak JR, Shivdasani R, Coetzee GA, Freedman ML. The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat Genet. 2009 Aug;41(8):882-4.
Verzi MP, Shivdasani RA. Wnt signaling in gut organogenesis. Organogenesis. 2008 Apr;4(2):87-91.
Verzi MP, Stanfel MN, Moses KA, Kim BM, Zhang Y, Schwartz RJ, Shivdasani RA, Zimmer WE. Role of the homeodomain transcription factor Bapx1 in mouse distal stomach development. Gastroenterology. 2009 May;136(5):1701-10.
Eeckhoute J, Lupien M, Meyer CA, Verzi MP, Shivdasani RA, Liu XS, Brown M. Cell-type selective chromatin remodeling defines the active subset of FOXA1-bound enhancers. Genome Res. 2009 Mar;19(3):372-80.
Verzi MP, Khan AH, Ito S, Shivdasani RA. Transcription factor foxq1 controls mucin gene expression and granule content in mouse stomach surface mucous cells. Gastroenterology. 2008 Aug;135(2):591-600.
Agarwal P, Verzi MP, Nguyen T, Hu J, Ehlers ML, McCulley DJ, Xu SM, Dodou E, Anderson JP, Wei ML, Black BL. The MADS box transcription factor MEF2C regulates melanocyte development and is a direct transcriptional target and partner of SOX10. Development. 2011 Jun;138(12):2555-65.
Verzi MP, Agarwal P, Brown C, McCulley DJ, Schwarz JJ, Black BL. The transcription factor MEF2C is required for craniofacial development. Dev Cell. 2007 Apr;12(4):645-52.