Biomedical Research Education & Training
Faculty Member

de Caestecker, Mark P., M.B., B.S., Ph.D.,
Associate Professor of Medicine
Associate Professor of Cell and Developmental Biology
Associate Professor of Surgery

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Phone Number: (615) 343-2844

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de Caestecker, Mark's picture
Academic history
B.A., Cambridge University, England
M.B., B.S., Middlesex Hospital, London
MRCP, Royal College of Physicians, United Kingdom
Ph.D., Manchester University, England
Fellowship, Manchester University School of Medicine
Post-doctoral , National Institutes of Health, Bethesda

Office Address   Mailing Address

C-3126 MCN

S3223 MCN 2372

Research Keywords
Kidney injury, regeneration and scarring; mechanisms of tissue regeneration and therapy; kidney development; Wilms tumor; intrauterine growth retardation and asymetric organ growth; BMP signaling, pulmonary vasculature and pulmonary arterial hypertension

Research Specialty
Kidney regeneration and therapy, kidney development, pulmonary vasculature, genetics, BMP signaling, IPS cells

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

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, 131(6), E983-94, 2012

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, 47(6), 1239-49, 2012

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, 152(6), 2503-16, 2011

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, 298(3), R833-42, 2010

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, 299(6), R1463-77, 2010

Lowery, JW, de Caestecker, MP. BMP signaling in vascular development and disease. Cytokine Growth Factor Rev, 21(4), 287-98, 2010 PMCID:2939258

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, 2010

Langworthy, M, Zhou, B, de Caestecker, M, Moeckel, G, Baldwin, HS. NFATc1 identifies a population of proximal tubule cell progenitors. J Am Soc Nephrol, 20(2), 311-21, 2009 PMCID:2637056

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, 20(4), 777-86, 2009 PMCID:2663829

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, 313(1), 234-45, 2008 PMCID:2699557

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, 294(1), L98-109, 2008

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, 236(8), 2321-30, 2007

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, 42(3), 474-81, 2007

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, 9(7), 589-600, 2007 PMCID:1941694

de Caestecker, MP. Angiopoietin-2 and glomerular proteinuria. J Am Soc Nephrol, 18(8), 2217-8, 2007

Boyle, S, de Caestecker, M. Role of transcriptional networks in coordinating early events during kidney development. Am J Physiol Renal Physiol, 291(1), F1-8, 2006

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, 17(5), 1283-91, 2006

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, 281(37), 27426-35, 2006

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, 17(9), 2504-12, 2006

de Caestecker, M. Serotonin signaling in pulmonary hypertension. Circ Res, 98(10), 1229-31, 2006

Frank, D, Johnson, J, de Caestecker, M. Bone morphogenetic protein 4 promotes vascular remodeling in hypoxic pulmonary hypertension. Chest, 128(6 Suppl), 590S-591S, 2005

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, 97(5), 496-504, 2005

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, 16(6), 1632-44, 2005

Chacko, Benoy M, Qin, Bin Y, Tiwari, Ashutosh, Shi, Genbin, Lam, Suvana, Hayward, Lawrence J, De Caestecker, Mark, Lin, Kai. Structural basis of heteromeric smad protein assembly in TGF-beta signaling. Mol Cell, 15(5), 813-23, 2004

de Caestecker, Mark. The transforming growth factor-beta superfamily of receptors. Cytokine Growth Factor Rev, 15(1), 1-11, 2004

Hayashida, Tomoko, Decaestecker, Mark, Schnaper, H William. Cross-talk between ERK MAP kinase and Smad signaling pathways enhances TGF-beta-dependent responses in human mesangial cells. FASEB J, 17(11), 1576-8, 2003

de Caestecker, Mark P, Bottomley, Martyn, Bhattacharyya, Sucharita, Payne, Tracie L, Roberts, Anita B, Yelick, Pamela C. The novel type I serine-threonine kinase receptor Alk8 binds TGF-beta in the presence of TGF-betaRII. Biochem Biophys Res Commun, 293(5), 1556-65, 2002

de Caestecker, M. P., Meyrick B. Bone Morphogenetic proteins, genetics and the pathophysiology of primary pulmonary hypertension. Respiratory Research 2: 193, 2001

Chacko, B M, Qin, B, Correia, J J, Lam, S S, de Caestecker, M P, Lin, K. The L3 loop and C-terminal phosphorylation jointly define Smad protein trimerization. Nat Struct Biol, 8(3), 248-53, 2001

De Caestecker, M, Meyrick, B. Bone morphogenetic proteins, genetics and the pathophysiology of primary pulmonary hypertension. Respir Res, 2(4), 193-7, 2001 PMCID:59576

Lee, D K, Park, S H, Yi, Y, Choi, S G, Lee, C, Parks, W T, Cho, H, de Caestecker, M P, Shaul, Y, Roberts, A B, Kim, S J. 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, 15(4), 455-66, 2001 PMCID:312630

Parks, W T, Frank, D B, Huff, C, Renfrew Haft, C, Martin, J, Meng, X, de Caestecker, M P, McNally, J G, Reddi, A, Taylor, S I, Roberts, A B, Wang, T, Lechleider, R J. Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases. J Biol Chem, 276(22), 19332-9, 2001

Qin, B Y, Chacko, B M, Lam, S S, de Caestecker, M P, Correia, J J, Lin, K. Structural basis of Smad1 activation by receptor kinase phosphorylation. Mol Cell, 8(6), 1303-12, 2001

Watanabe, H, de Caestecker, M P, 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, 276(17), 14466-73, 2001

Kim, R H, Wang, D, Tsang, M, Martin, J, Huff, C, de Caestecker, M P, Parks, W T, Meng, X, Lechleider, R J, Wang, T, Roberts, A B. A novel smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-beta signal transduction. Genes Dev, 14(13), 1605-16, 2000 PMCID:316742

Larisch, S, Yi, Y, Lotan, R, Kerner, H, Eimerl, S, Tony Parks, W, Gottfried, Y, Birkey Reffey, S, de Caestecker, M P, Danielpour, D, Book-Melamed, N, Timberg, R, Duckett, C S, Lechleider, R J, Steller, H, Orly, J, Kim, S J, Roberts, A B. A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif. Nat Cell Biol, 2(12), 915-21, 2000

Tsang, M, Kim, R, de Caestecker, M P, Kudoh, T, Roberts, A B, Dawid, I B. Zebrafish nma is involved in TGFbeta family signaling. Genesis, 28(2), 47-57, 2000

Yahata, T, de Caestecker, M P, Lechleider, R J, Andriole, S, Roberts, A B, Isselbacher, K J, 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, 275(12), 8825-34, 2000

de Caestecker, M P, Piek, E, Roberts, A B. Role of transforming growth factor-beta signaling in cancer. J Natl Cancer Inst, 92(17), 1388-402, 2000

de Caestecker, M P, Yahata, T, Wang, D, Parks, W T, Huang, S, Hill, C S, Shioda, T, Roberts, A B, Lechleider, R J. The Smad4 activation domain (SAD) is a proline-rich, p300-dependent transcriptional activation domain. J Biol Chem, 275(3), 2115-22, 2000

Poncelet, A C, de Caestecker, M P, Schnaper, H W. The transforming growth factor-beta/SMAD signaling pathway is present and functional in human mesangial cells. Kidney Int, 56(4), 1354-65, 1999

Shioda, T, Lechleider, R J, Dunwoodie, S L, Li, H, Yahata, T, de Caestecker, M P, Fenner, M H, Roberts, A B, Isselbacher, K J. Transcriptional activating activity of Smad4: roles of SMAD hetero-oligomerization and enhancement by an associating transactivator. Proc Natl Acad Sci U S A, 95(17), 9785-90, 1998 PMCID:21414

Vindevoghel, L, Lechleider, R J, Kon, A, de Caestecker, M P, Uitto, J, Roberts, A B, 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, 95(25), 14769-74, 1998 PMCID:24524

de Caestecker, M P, Parks, W T, Frank, C J, Castagnino, P, Bottaro, D P, Roberts, A B, Lechleider, R J. Smad2 transduces common signals from receptor serine-threonine and tyrosine kinases. Genes Dev, 12(11), 1587-92, 1998 PMCID:316877

de Caestecker, M P, Hemmati, P, Larisch-Bloch, S, Ajmera, R, Roberts, A B, Lechleider, R J. Characterization of functional domains within Smad4/DPC4. J Biol Chem, 272(21), 13690-6, 1997

Lechleider, R J, de Caestecker, M P, Dehejia, A, Polymeropoulos, M H, Roberts, A B. Serine phosphorylation, chromosomal localization, and transforming growth factor-beta signal transduction by human bsp-1. J Biol Chem, 271(30), 17617-20, 1996

Mallick, N P, de Caestecker, M P. The changing population on renal replacement therapy: its clinical and economic impact in Europe. Nephrol Dial Transplant, 11 Suppl 2, 2-5, 1996

de Caestecker, M P, Bottomley, M, Telfer, B A, Hutchinson, I V, Vose, B M, Ballardie, F W. Detection of abnormal peripheral blood mononuclear cell cytokine networks in human IgA nephropathy. Kidney Int, 44(6), 1298-308, 1993

de Caestecker, M P, Ballardie, F W. Volumetric analysis of urinary erythrocytes: a standardized methodology to localize the source of haematuria. Am J Nephrol, 12(1-2), 41-8, 1992

de Caestecker, M P, Telfer, B A, Hutchinson, I V, Ballardie, F W. 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, 154(1), 11-20, 1992

de Caestecker, M P, Ballardie, F W. Unexplained haematuria. BMJ, 301(6762), 1171-2, 1990 PMCID:1664318

de Caestecker, M P, Hall, C L, MacIver, A G. Atypical antiglomerular basement membrane disease associated with thin membrane nephropathy. Nephrol Dial Transplant, 5(11), 909-13, 1990

de Caestecker, M P, Hall, C L, Basterfield, P T, Smith, J G. Localisation of haematuria by red cell analysers and phase contrast microscopy. Nephron, 52(2), 170-3, 1989

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