de Caestecker Lab

Our laboratory currently has two major NIH funded research interests:

1) We are studying the innate mechanisms regulating progenitor cell expansion and tissue regeneration following acute kidney injury, and evaluating the use of small molecules identified from a high content screen in Zebrafish embryos for their ability to accelerate these innate mechanisms of tissue regeneration following injury.  To this end we are developing a number of assays and tools to evaluate renal epithelial cell regenerative capacity in vivo, and are actively exploring the role of chromatin in regulating these regenerative events.

2) Our lab is also studying the role of BMP signaling in regulating reactivity and remodeling of the lung vasculature both in normal individuals, and in patients and mice carrying a number of different heritable mutations in the BMP type 2 receptor (BMPR2) locus.  To do this we are developing mouse genetic models, reporters and along with Kevin Ess and Aaron Bowman, optimizing reprogramming conditions to develop inducible pluripotent stem cells (IPSCs) from patients with hereditary pulmonary arterial hypertension (HPAH). We are also testing a variety of different protocols to promote efficient endothelial and smooth muscle cell differentiation of IPSCs in order to study the biology of BMP signaling defects in the vasculature of patients with HPAH.

Other interests in the laboratory include the development of a genetic model of Wilms’ tumorgenesis in mice, and the analysis of signaling pathways governing asymmetric organ growth in mice with late gestational placental insufficiency.

Publications

Featured publications

  1. Heterozygous null bone morphogenetic protein receptor type 2 mutations promote SRC kinase-dependent caveolar trafficking defects and endothelial dysfunction in pulmonary arterial hypertension. Prewitt AR, Ghose S, Frump AL, Datta A, Austin ED, Kenworthy AK, de Caestecker MP (2015) J Biol Chem 290(2): 960-71
    › Primary publication · 25411245 (PubMed) · PMC4294523 (PubMed Central)
  2. CITED1 confers stemness to Wilms tumor and enhances tumorigenic responses when enriched in the nucleus. Murphy AJ, Pierce J, de Caestecker C, Ayers GD, Zhao A, Krebs JR, Saito-Diaz VK, Lee E, Perantoni AO, de Caestecker MP, Lovvorn HN (2014) Oncotarget 5(2): 386-402
    › Primary publication · 24481423 (PubMed) · PMC3964215 (PubMed Central)
  3. A PTBA small molecule enhances recovery and reduces postinjury fibrosis after aristolochic acid-induced kidney injury. Novitskaya T, McDermott L, Zhang KX, Chiba T, Paueksakon P, Hukriede NA, de Caestecker MP (2014) Am J Physiol Renal Physiol 306(5): F496-504
    › Primary publication · 24370591 (PubMed) · PMC3949031 (PubMed Central)
  4. Abnormal trafficking of endogenously expressed BMPR2 mutant allelic products in patients with heritable pulmonary arterial hypertension. Frump AL, Lowery JW, Hamid R, Austin ED, de Caestecker M (2013) PLoS One 8(11): e80319
    › Primary publication · 24224048 (PubMed) · PMC3818254 (PubMed Central)
  5. Aberrant activation, nuclear localization, and phosphorylation of Yes-associated protein-1 in the embryonic kidney and Wilms tumor. Murphy AJ, Pierce J, de Caestecker C, Libes J, Neblett D, de Caestecker M, Perantoni AO, Tanigawa S, Anderson JR, Dome JS, Das A, Carroll TJ, Lovvorn HN (2014) Pediatr Blood Cancer 61(2): 198-205
    › Primary publication · 24115727 (PubMed) · PMC3955491 (PubMed Central)
  6. Kidney regeneration: common themes from the embryo to the adult. Cirio MC, de Groh ED, de Caestecker MP, Davidson AJ, Hukriede NA (2014) Pediatr Nephrol 29(4): 553-64
    › Primary publication · 24005792 (PubMed) · PMC3944192 (PubMed Central)
  7. Ischemia-reperfusion model of acute kidney injury and post injury fibrosis in mice. Skrypnyk NI, Harris RC, de Caestecker MP (2013) J Vis Exp (78)
    › Primary publication · 23963468 (PubMed) · PMC3854859 (PubMed Central)
  8. Histone deacetylase inhibitor enhances recovery after AKI. Cianciolo Cosentino C, Skrypnyk NI, Brilli LL, Chiba T, Novitskaya T, Woods C, West J, Korotchenko VN, McDermott L, Day BW, Davidson AJ, Harris RC, de Caestecker MP, Hukriede NA (2013) J Am Soc Nephrol 24(6): 943-53
    › Primary publication · 23620402 (PubMed) · PMC3665399 (PubMed Central)
  9. Deletion of fibroblast growth factor receptor 2 from the peri-wolffian duct stroma leads to ureteric induction abnormalities and vesicoureteral reflux. Walker KA, Sims-Lucas S, Di Giovanni VE, Schaefer C, Sunseri WM, Novitskaya T, de Caestecker MP, Chen F, Bates CM (2013) PLoS One 8(2): e56062
    › Primary publication · 23409123 (PubMed) · PMC3567073 (PubMed Central)
  10. CITED1 expression in liver development and hepatoblastoma. Murphy AJ, de Caestecker C, Pierce J, Boyle SC, Ayers GD, Zhao Z, Libes JM, Correa H, Walter T, Huppert SS, Perantoni AO, de Caestecker MP, Lovvorn HN (2012) Neoplasia 14(12): 1153-63
    › Primary publication · 23308048 (PubMed) · PMC3540941 (PubMed Central)

Community Leaders

Contact Information

1161 21st Ave. S.
3223 MCN
Nashville, TN 37232
USA

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Keywords & MeSH Terms

MeSH terms are retrieved from PubMed records. Learn more.

Key: MeSH Term Keyword

BAC transgenic mice BMP signaling breast cancer cell adhesion COS Cells Cross-Linking Reagents Cytokines Familial Primary Pulmonary Hypertension Fibroblast Growth Factors Imidazoles Indoles In Situ Hybridization lineage tracing Membrane Proteins Mice, SCID multipotent epithelial progenitor cells phosphorylation Proteinuria Pulmonary Artery pulmonary hypertension Reagent Strips Receptor, Transforming Growth Factor-beta Type II Receptor Protein-Tyrosine Kinases renal development Saccharomyces cerevisiae Single-Blind Method Smad2 Protein Thiazoles Tissue Distribution transcription factor vascular remodeling Wilms tumor