Mark P. de Caestecker, M.B.B.S., Ph.D.

Associate Professor

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Faculty Appointments
Associate Professor of Medicine Associate Professor of SurgeryAssociate Professor of Cell and Developmental Biology
Ph.D., Medicine, University of Manchester, Manchester, United KingdomM.B.B.S., Internal Medicine, London University, London, United KingdomM.A., Medicine, University of Cambridge, Cambridge, United KingdomB.A., Medical Sciences, University of Cambridge, Cambridge, United Kingdom
Office Address
S3223 MCN
TN 2372
Research Description
There are three main areas of research in my lab:

1) Our laboratory is interested in the mechanisms regulating kidney development and how these processes are abnormally regulated in kidney injury and malignancy (Wilms tumor). Studes from my lab have mainly focused on the role of Cited1, 2 and 4, a family of transcriptional co-activators that are involved in regulating fate and migration of epithelial progenitor cells in during renal development. In addition, based on our evaluation of Cited1 knockout mice, we are investigating the fetal programming defects resulting from intrauterine growth retardation that promote abnormal embryonic kidney development and chronic kidney disease in adults.

2) We are currently extending our developmental studies to explore how some of these developmental regulated pathways are reactivated in regerenating tissues following acute kidney injury and studying their role in promoting normal tissue regeneration. Based on these studies we are testing novel thereapeutic approaches, identified from high content screens in zebrafish embryos (in collaboration with Neil Hukreide from the University of Pittsburgh) , that enhance these regnerative developmental programs, increase the rate of recovery and reduce long term scarring following acute kidney injury in mice.

3) The other focus in my lab is on the functional role of BMP signaling in pulmonary hypertension. Human genetic studies indicate that this signaling pathway plays an important role in modifying pulmonary vascular responses in disease. Studies from my lab have shown that Bmp signaling exerts distinct opposing, cell specific effects on pulmonary vascular remodeling and tone. We are currently using genetic models in mice and patient derived IPS cells to evaluate effect of inherited mutations in the BMP type 2 receptor, BMPR2, on pulmonary vascular cell function, and using these approaches to evaluate the use of mutation-specific therapies to improve pulmonary vascular function in patients with heritable forms of pulmonary hypertension
Research Keywords
Kidney regeneration and therapy, kidney development, pulmonary vasculature, genetics, BMP signaling, IPS cells
Murphy AJ, Axt JR, de Caestecker C, Pierce J, Correa H, Seeley EH, Caprioli RM, Newton MW, de Caestecker MP, Lovvorn HN. Molecular characterization of Wilms' tumor from a resource-constrained region of sub-Saharan Africa. Int. J. Cancer [print-electronic]. 2012 Sep 9/15/2012; 131(6): E983-94. PMID: 22437966, PMCID: PMC3402639, DOI: 10.1002/ijc.27544, ISSN: 1097-0215.

Murphy AJ, Pierce J, de Caestecker C, Taylor C, Anderson JR, Perantoni AO, de Caestecker MP, Lovvorn HN. SIX2 and CITED1, markers of nephronic progenitor self-renewal, remain active in primitive elements of Wilms' tumor. J. Pediatr. Surg. 2012 Jun; 47(6): 1239-49. PMID: 22703800, PMCID: PMC3377935, PII: S0022-3468(12)00274-6, DOI: 10.1016/j.jpedsurg.2012.03.034, ISSN: 1531-5037.

Novitskaya T, Baserga M, de Caestecker MP. Organ-specific defects in insulin-like growth factor and insulin receptor signaling in late gestational asymmetric intrauterine growth restriction in Cited1 mutant mice. Endocrinology [print-electronic]. 2011 Jun; 152(6): 2503-16. PMID: 21486933, PMCID: PMC3100618, PII: en.2010-1385, DOI: 10.1210/en.2010-1385, ISSN: 1945-7170.

Lowery JW, Frump AL, Anderson L, DiCarlo GE, Jones MT, de Caestecker MP. ID family protein expression and regulation in hypoxic pulmonary hypertension. Am. J. Physiol. Regul. Integr. Comp. Physiol [print-electronic]. 2010 Dec; 299(6): R1463-77. PMID: 20881097, PMCID: PMC3007180, PII: ajpregu.00866.2009, DOI: 10.1152/ajpregu.00866.2009, ISSN: 1522-1490.

Lowery JW, de Caestecker MP. BMP signaling in vascular development and disease. Cytokine Growth Factor Rev [print-electronic]. 2010 Aug; 21(4): 287-98. PMID: 20674464, PMCID: PMC2939258, PII: S1359-6101(10)00047-X, DOI: 10.1016/j.cytogfr.2010.06.001, ISSN: 1879-0305.

Zhang MZ, Su Y, Yao B, Zheng W, Decaestecker M, Harris RC. Assessing the application of tissue microarray technology to kidney research. J. Histochem. Cytochem [print-electronic]. 2010 May; 58(5): 413-20. PMID: 20086233, PMCID: PMC2857813, PII: jhc.2009.954966, DOI: 10.1369/jhc.2009.954966, ISSN: 1551-5044.

Anderson L, Lowery JW, Frank DB, Novitskaya T, Jones M, Mortlock DP, Chandler RL, de Caestecker MP. Bmp2 and Bmp4 exert opposing effects in hypoxic pulmonary hypertension. Am. J. Physiol. Regul. Integr. Comp. Physiol [print-electronic]. 2010 Mar; 298(3): R833-42. PMID: 20042692, PMCID: PMC2838658, PII: 00534.2009, DOI: 10.1152/ajpregu.00534.2009, ISSN: 1522-1490.

Sparrow DB, Boyle SC, Sams RS, Mazuruk B, Zhang L, Moeckel GW, Dunwoodie SL, de Caestecker MP. Placental insufficiency associated with loss of Cited1 causes renal medullary dysplasia. J. Am. Soc. Nephrol [print-electronic]. 2009 Apr; 20(4): 777-86. PMID: 19297558, PMCID: PMC2663829, PII: ASN.2008050547, DOI: 10.1681/ASN.2008050547, ISSN: 1533-3450.

Langworthy M, Zhou B, de Caestecker M, Moeckel G, Baldwin HS. NFATc1 identifies a population of proximal tubule cell progenitors. J. Am. Soc. Nephrol [print-electronic]. 2009 Feb; 20(2): 311-21. PMID: 19118153, PMCID: PMC2637056, PII: ASN.2008010094, DOI: 10.1681/ASN.2008010094, ISSN: 1533-3450.

Frank DB, Lowery J, Anderson L, Brink M, Reese J, de Caestecker M. Increased susceptibility to hypoxic pulmonary hypertension in Bmpr2 mutant mice is associated with endothelial dysfunction in the pulmonary vasculature. Am. J. Physiol. Lung Cell Mol. Physiol [print-electronic]. 2008 Jan; 294(1): L98-109. PMID: 18024717, PII: 00034.2007, DOI: 10.1152/ajplung.00034.2007, ISSN: 1040-0605.

Boyle S, Misfeldt A, Chandler KJ, Deal KK, Southard-Smith EM, Mortlock DP, Baldwin HS, de Caestecker M. Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia. Dev. Biol [print-electronic]. 2008 Jan 1/1/2008; 313(1): 234-45. PMID: 18061157, PMCID: PMC2699557, PII: S0012-1606(07)01457-1, DOI: 10.1016/j.ydbio.2007.10.014, ISSN: 1095-564X.

Boyle S, Shioda T, Perantoni AO, de Caestecker M. Cited1 and Cited2 are differentially expressed in the developing kidney but are not required for nephrogenesis. Dev. Dyn. 2007 Aug; 236(8): 2321-30. PMID: 17615577, DOI: 10.1002/dvdy.21242, ISSN: 1058-8388.

de Caestecker MP. Angiopoietin-2 and glomerular proteinuria [editorial]. J. Am. Soc. Nephrol [print-electronic]. 2007 Aug; 18(8): 2217-8. PMID: 17625115, PII: ASN.2007060650, DOI: 10.1681/ASN.2007060650, ISSN: 1046-6673.

Lovvorn HN, Westrup J, Opperman S, Boyle S, Shi G, Anderson J, Perlman EJ, Perantoni AO, Wills M, de Caestecker M. CITED1 expression in Wilms' tumor and embryonic kidney. Neoplasia. 2007 Jul; 9(7): 589-600. PMID: 17710162, PMCID: PMC1941694, ISSN: 1476-5586.

Lovvorn HN, Boyle S, Shi G, Shyr Y, Wills ML, Perantoni AO, de Caestecker M. Wilms' tumorigenesis is altered by misexpression of the transcriptional co-activator, CITED1. J. Pediatr. Surg. 2007 Mar; 42(3): 474-81. PMID: 17336183, PMCID: PMC3028602, PII: S0022-3468(06)00796-2, DOI: 10.1016/j.jpedsurg.2006.10.054, ISSN: 1531-5037.

Shi G, Boyle SC, Sparrow DB, Dunwoodie SL, Shioda T, de Caestecker MP. The transcriptional activity of CITED1 is regulated by phosphorylation in a cell cycle-dependent manner. J. Biol. Chem [print-electronic]. 2006 Sep 9/15/2006; 281(37): 27426-35. PMID: 16864582, PII: M602631200, DOI: 10.1074/jbc.M602631200, ISSN: 0021-9258.

Wang S, de Caestecker M, Kopp J, Mitu G, Lapage J, Hirschberg R. Renal bone morphogenetic protein-7 protects against diabetic nephropathy. J. Am. Soc. Nephrol [print-electronic]. 2006 Sep; 17(9): 2504-12. PMID: 16899516, PII: ASN.2006030278, DOI: 10.1681/ASN.2006030278, ISSN: 1046-6673.

Boyle S, de Caestecker M. Role of transcriptional networks in coordinating early events during kidney development. Am. J. Physiol. Renal Physiol. 2006 Jul; 291(1): F1-8. PMID: 16760375, PII: 291/1/F1, DOI: 10.1152/ajprenal.00447.2005, ISSN: 1931-857X.

de Caestecker M. Serotonin signaling in pulmonary hypertension [editorial]. Circ. Res. 2006 May 5/26/2006; 98(10): 1229-31. PMID: 16728665, PII: 98/10/1229, DOI: 10.1161/01.RES.0000225927.04710.33, ISSN: 1524-4571.

Chen J, Boyle S, Zhao M, Su W, Takahashi K, Davis L, Decaestecker M, Takahashi T, Breyer MD, Hao CM. Differential expression of the intermediate filament protein nestin during renal development and its localization in adult podocytes. J. Am. Soc. Nephrol [print-electronic]. 2006 May; 17(5): 1283-91. PMID: 16571784, PII: ASN.2005101032, DOI: 10.1681/ASN.2005101032, ISSN: 1046-6673.

Frank D, Johnson J, de Caestecker M. Bone morphogenetic protein 4 promotes vascular remodeling in hypoxic pulmonary hypertension. Chest. 2005 Dec; 128(6 Suppl): 590S-591S. PMID: 16373851, PII: 128/6_suppl/590S, DOI: 10.1378/chest.128.6_suppl.590S, ISSN: 0012-3692.

Frank DB, Abtahi A, Yamaguchi DJ, Manning S, Shyr Y, Pozzi A, Baldwin HS, Johnson JE, de Caestecker MP. Bone morphogenetic protein 4 promotes pulmonary vascular remodeling in hypoxic pulmonary hypertension. Circ. Res [print-electronic]. 2005 Sep 9/2/2005; 97(5): 496-504. PMID: 16100039, PII: 01.RES.0000181152.65534.07, DOI: 10.1161/01.RES.0000181152.65534.07, ISSN: 1524-4571.

Plisov S, Tsang M, Shi G, Boyle S, Yoshino K, Dunwoodie SL, Dawid IB, Shioda T, Perantoni AO, de Caestecker MP. Cited1 is a bifunctional transcriptional cofactor that regulates early nephronic patterning. J. Am. Soc. Nephrol [print-electronic]. 2005 Jun; 16(6): 1632-44. PMID: 15843474, PII: ASN.2004060476, DOI: 10.1681/ASN.2004060476, ISSN: 1046-6673.

Chacko BM, Qin BY, Tiwari A, Shi G, Lam S, Hayward LJ, De Caestecker M, Lin K. Structural basis of heteromeric smad protein assembly in TGF-beta signaling. Mol. Cell. 2004 Sep 9/10/2004; 15(5): 813-23. PMID: 15350224, PII: S1097276504004381, DOI: 10.1016/j.molcel.2004.07.016, ISSN: 1097-2765.

de Caestecker M. The transforming growth factor-beta superfamily of receptors. Cytokine Growth Factor Rev. 2004 Feb; 15(1): 1-11. PMID: 14746809, PII: S135961010300100X, ISSN: 1359-6101.

Hayashida T, Decaestecker M, Schnaper HW. Cross-talk between ERK MAP kinase and Smad signaling pathways enhances TGF-beta-dependent responses in human mesangial cells. FASEB J [print-electronic]. 2003 Aug; 17(11): 1576-8. PMID: 12824291, PII: 03-0037fje, DOI: 10.1096/fj.03-0037fje, ISSN: 1530-6860.

de Caestecker MP, Bottomley M, Bhattacharyya S, Payne TL, Roberts AB, Yelick PC. The novel type I serine-threonine kinase receptor Alk8 binds TGF-beta in the presence of TGF-betaRII. Biochem. Biophys. Res. Commun. 2002 May 5/24/2002; 293(5): 1556-65. PMID: 12054694, PII: S0006-291X(02)00424-2, DOI: 10.1016/S0006-291X(02)00424-2, ISSN: 0006-291X.

Qin BY, Chacko BM, Lam SS, de Caestecker MP, Correia JJ, Lin K. Structural basis of Smad1 activation by receptor kinase phosphorylation. Mol. Cell. 2001 Dec; 8(6): 1303-12. PMID: 11779505, PII: S1097-2765(01)00417-8, ISSN: 1097-2765.

Parks WT, Frank DB, Huff C, Renfrew Haft C, Martin J, Meng X, de Caestecker MP, McNally JG, Reddi A, Taylor SI, Roberts AB, Wang T, Lechleider RJ. Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases. J. Biol. Chem [print-electronic]. 2001 Jun 6/1/2001; 276(22): 19332-9. PMID: 11279102, PII: M100606200, DOI: 10.1074/jbc.M100606200, ISSN: 0021-9258.

Watanabe H, de Caestecker MP, Yamada Y. Transcriptional cross-talk between Smad, ERK1/2, and p38 mitogen-activated protein kinase pathways regulates transforming growth factor-beta-induced aggrecan gene expression in chondrogenic ATDC5 cells. J. Biol. Chem [print-electronic]. 2001 Apr 4/27/2001; 276(17): 14466-73. PMID: 11278290, PII: M005724200, DOI: 10.1074/jbc.M005724200, ISSN: 0021-9258.

Chacko BM, Qin B, Correia JJ, Lam SS, de Caestecker MP, Lin K. The L3 loop and C-terminal phosphorylation jointly define Smad protein trimerization. Nat. Struct. Biol. 2001 Mar; 8(3): 248-53. PMID: 11224571, PII: 84995, DOI: 10.1038/84995, ISSN: 1072-8368.

Lee DK, Park SH, Yi Y, Choi SG, Lee C, Parks WT, Cho H, de Caestecker MP, Shaul Y, Roberts AB, Kim SJ. The hepatitis B virus encoded oncoprotein pX amplifies TGF-beta family signaling through direct interaction with Smad4: potential mechanism of hepatitis B virus-induced liver fibrosis. Genes Dev. 2001 Feb 2/15/2001; 15(4): 455-66. PMID: 11230153, PMCID: PMC312630, DOI: 10.1101/gad.856201, ISSN: 0890-9369.

De Caestecker M, Meyrick B. Bone morphogenetic proteins, genetics and the pathophysiology of primary pulmonary hypertension. Respir. Res [print-electronic]. 2001; 2(4): 193-7. PMID: 11686884, PMCID: PMC59576, ISSN: 1465-9921.

Larisch S, Yi Y, Lotan R, Kerner H, Eimerl S, Tony Parks W, Gottfried Y, Birkey Reffey S, de Caestecker MP, Danielpour D, Book-Melamed N, Timberg R, Duckett CS, Lechleider RJ, Steller H, Orly J, Kim SJ, Roberts AB. A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif. Nat. Cell Biol. 2000 Dec; 2(12): 915-21. PMID: 11146656, DOI: 10.1038/35046566, ISSN: 1465-7392.

Tsang M, Kim R, de Caestecker MP, Kudoh T, Roberts AB, Dawid IB. Zebrafish nma is involved in TGFbeta family signaling. Genesis. 2000 Oct; 28(2): 47-57. PMID: 11064421, PII: 10.1002/1526-968X(200010)28:2<47::AID-GENE20>3.0.CO;2-S, ISSN: 1526-954X.

de Caestecker MP, Piek E, Roberts AB. Role of transforming growth factor-beta signaling in cancer. J. Natl. Cancer Inst. 2000 Sep 9/6/2000; 92(17): 1388-402. PMID: 10974075, ISSN: 0027-8874.

Kim RH, Wang D, Tsang M, Martin J, Huff C, de Caestecker MP, Parks WT, Meng X, Lechleider RJ, Wang T, Roberts AB. A novel smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-beta signal transduction. Genes Dev. 2000 Jul 7/1/2000; 14(13): 1605-16. PMID: 10887155, PMCID: PMC316742, ISSN: 0890-9369.

Yahata T, de Caestecker MP, Lechleider RJ, Andriole S, Roberts AB, Isselbacher KJ, Shioda T. The MSG1 non-DNA-binding transactivator binds to the p300/CBP coactivators, enhancing their functional link to the Smad transcription factors. J. Biol. Chem. 2000 Mar 3/24/2000; 275(12): 8825-34. PMID: 10722728, ISSN: 0021-9258.

de Caestecker MP, Yahata T, Wang D, Parks WT, Huang S, Hill CS, Shioda T, Roberts AB, Lechleider RJ. The Smad4 activation domain (SAD) is a proline-rich, p300-dependent transcriptional activation domain. J. Biol. Chem. 2000 Jan 1/21/2000; 275(3): 2115-22. PMID: 10636916, ISSN: 0021-9258.

Poncelet AC, de Caestecker MP, Schnaper HW. The transforming growth factor-beta/SMAD signaling pathway is present and functional in human mesangial cells. Kidney Int. 1999 Oct; 56(4): 1354-65. PMID: 10504488, PII: kid680, DOI: 10.1046/j.1523-1755.1999.00680.x, ISSN: 0085-2538.

Vindevoghel L, Lechleider RJ, Kon A, de Caestecker MP, Uitto J, Roberts AB, Mauviel A. SMAD3/4-dependent transcriptional activation of the human type VII collagen gene (COL7A1) promoter by transforming growth factor beta. Proc. Natl. Acad. Sci. U.S.A. 1998 Dec 12/8/1998; 95(25): 14769-74. PMID: 9843964, PMCID: PMC24524, ISSN: 0027-8424.

Shioda T, Lechleider RJ, Dunwoodie SL, Li H, Yahata T, de Caestecker MP, Fenner MH, Roberts AB, Isselbacher KJ. Transcriptional activating activity of Smad4: roles of SMAD hetero-oligomerization and enhancement by an associating transactivator. Proc. Natl. Acad. Sci. U.S.A. 1998 Aug 8/18/1998; 95(17): 9785-90. PMID: 9707553, PMCID: PMC21414, ISSN: 0027-8424.

de Caestecker MP, Parks WT, Frank CJ, Castagnino P, Bottaro DP, Roberts AB, Lechleider RJ. Smad2 transduces common signals from receptor serine-threonine and tyrosine kinases. Genes Dev. 1998 Jun 6/1/1998; 12(11): 1587-92. PMID: 9620846, PMCID: PMC316877, ISSN: 0890-9369.

de Caestecker MP, Hemmati P, Larisch-Bloch S, Ajmera R, Roberts AB, Lechleider RJ. Characterization of functional domains within Smad4/DPC4. J. Biol. Chem. 1997 May 5/23/1997; 272(21): 13690-6. PMID: 9153220, ISSN: 0021-9258.

Lechleider RJ, de Caestecker MP, Dehejia A, Polymeropoulos MH, Roberts AB. Serine phosphorylation, chromosomal localization, and transforming growth factor-beta signal transduction by human bsp-1. J. Biol. Chem. 1996 Jul 7/26/1996; 271(30): 17617-20. PMID: 8663601, ISSN: 0021-9258.

Mallick NP, de Caestecker MP. The changing population on renal replacement therapy: its clinical and economic impact in Europe. Nephrol. Dial. Transplant. 1996; 11 Suppl 2: 2-5. PMID: 8803985, ISSN: 0931-0509.

de Caestecker MP, Bottomley M, Telfer BA, Hutchinson IV, Vose BM, Ballardie FW. Detection of abnormal peripheral blood mononuclear cell cytokine networks in human IgA nephropathy. Kidney Int. 1993 Dec; 44(6): 1298-308. PMID: 8301931, ISSN: 0085-2538.

de Caestecker MP, Telfer BA, Hutchinson IV, Ballardie FW. The detection of intracytoplasmic interleukin-1 alpha, interleukin-1 beta and tumour necrosis factor alpha expression in human monocytes using two colour immunofluorescence flow cytometry. J. Immunol. Methods. 1992 Sep 9/18/1992; 154(1): 11-20. PMID: 1401937, PII: 0022-1759(92)90207-A, ISSN: 0022-1759.

de Caestecker MP, Ballardie FW. Volumetric analysis of urinary erythrocytes: a standardized methodology to localize the source of haematuria. Am. J. Nephrol. 1992; 12(1-2): 41-8. PMID: 1415364, ISSN: 0250-8095.

de Caestecker MP, Ballardie FW. Unexplained haematuria [editorial]. BMJ. 1990 Nov 11/24/1990; 301(6762): 1171-2. PMID: 2261550, PMCID: PMC1664318, ISSN: 0959-8138.

de Caestecker MP, Hall CL, MacIver AG. Atypical antiglomerular basement membrane disease associated with thin membrane nephropathy. Nephrol. Dial. Transplant. 1990; 5(11): 909-13. PMID: 2127824, ISSN: 0931-0509.

de Caestecker MP, Hall CL, Basterfield PT, Smith JG. Localisation of haematuria by red cell analysers and phase contrast microscopy. Nephron. 1989; 52(2): 170-3. PMID: 2662043, ISSN: 1660-8151.

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Posted: 10/29/2012
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