Chuxia Deng, Ph.D. : NIDDK

Chuxia Deng, Ph.D.

NIDDK, National Institutes of Health
Building 10, Room 9N105
10 Center Dr.
Bethesda, MD 20892-1812
Tel: 301-402-7225
Fax: 301-480-1135

Education / Previous Training and Experience:
B.S., Nanchong Normal University, China, 1981
M.S., Institute of Hydrobiology, Chinese Academy of Science, 1984
Ph.D., University of Utah, 1992

Research Statement:

The primary interest of my group is mammalian development and tumorigenesis using animal model systems. We have the following three projects.

Functions of fibroblast growth factor receptors (FGFRs)

FGFRs constitute a family of four membrane-spanning tyrosine kinases, which serve as high affinity receptors for at least 22 growth factors. It has been shown that mutations in FGF receptors are responsible for at least nine human inherited diseases, all of which are caused by single amino acid mutations and exhibit extensive craniofacial, axial, and/or appendicular bone abnormalities. To study functions of FGFs/FGFRs signals in development and to gain insights into mechanisms underlying these inherited diseases, mice that carry a variety of mutations including complete, isoform, and conditional knockouts, and point mutations that mimic the human diseases have been created through gene targeting. Functional analysis of these mutant mice has been carried out.

Functions of Smad genes

Smads constitute a gene family of eight members that serve as intracellular mediators of TGF-beta signals. We have generated mouse mutants carrying targeted mutations in SMAD2-5. Our preliminary analysis on the mutant mice has revealed distinct functions of these genes in multiple biological processes.

Functions of Brca1 gene

We are studying functions of the breast tumor suppressor gene Brca1 in mammary gland development and tumor formation. Breast cancer is the most common cancer and the second leading cause of cancer mortality in women, with approximately one in nine being affected over their lifetime. Analyzing our Brca1-null, isoform, or conditional knockout models, we showed that BRCA1 is essential for genetic stability. Loss of BRCA1 increases mutation rates of all genes, including tumor suppressors and oncogenes, which results in tumor formation. We are continuing to study mechanisms of BRCA1 associated tumorigenesis and seeking efficient ways to prevent the transformation process from happening in Brca1 mutant cells.

Selected Publications:

1. Aulehla A, Wiegraebe W, Baubet V, Wahl MB, Deng C, Taketo M, Lewandoski M, Pourquie A beta-catenin gradient links the clock and wavefront systems in mouse embryo segmentation. Nat Cell Biol(10): 186-93, 2008. [Full Text/Abstract]

2. Yin L, Du X, Li C, Xu X, Chen Z, Su N, Zhao L, Qi H, Li F, Xue J, Yang J, Jin M, Deng C, Chen L A Pro253Arg mutation in fibroblast growth factor receptor 2 (Fgfr2) causes skeleton malformation mimicking human Apert syndrome by affecting both chondrogenesis and osteogenesis. Bone(42): 631-643, 2008. [Full Text/Abstract]

3. Ahn BH, Kim HS, Song S, Lee IH, Liu J, Vassilopoulos A, Deng CX, Finkel T A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci U S A(105): 14447-52, 2008. [Full Text/Abstract]

4. Colak D, Mori T, Brill MS, Pfeifer A, Falk S, Deng C, Monteiro R, Mummery C, Sommer L, Gotz M Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells. J Neurosci(28): 434-46, 2008. [Full Text/Abstract]

5. Nie X, Deng CX, Wang Q, Jiao K Disruption of Smad4 in neural crest cells leads to mid-gestation death with pharyngeal arch, craniofacial and cardiac defects. Dev Biol(316): 417-30, 2008. [Full Text/Abstract]

6. Kang JS, Tian JH, Pan PY, Zald P, Li C, Deng C, Sheng ZH Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation. Cell(132): 137-48, 2008. [Full Text/Abstract]

7. Xun Xu, Jun Han, Yoshihiro Ito, Pablo Bringas, Jr., Chuxia Deng, and Yang Chai Ectodermal Smad4 and p38 MAPK are functionally redundant in mediating TGF-Beta/BMP signaling during tooth and palate development Developmental Cell: 15(2):322-9, 2008.

8. Vassilopoulos A, Wang RH, Petrovas C, Ambrozak D, Koup R, Deng CX Identification and characterization of cancer initiating cells from BRCA1 related mammary tumors using markers for normal mammary stem cells. Int J Biol Sci(4): 133-42, 2008. [Full Text/Abstract]

9. Wang RH, Sengupta K, Li C, Kim HS, Cao L, Xiao C, Kim S, Xu X, Zheng Y, Chilton B, Jia R, Zheng ZM, Appella E, Wang XW, Ried T, Deng CX Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell(14): 312-23, 2008. [Full Text/Abstract]

10. Wang RH, Zheng Y, Kim HS, Xu X, Cao L, Luhasen T, Lee MH, Xiao C, Vassilopoulos A, Chen W, Gardner K, Man YG, Hung MC, Finkel T, Deng CX Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis. Mol Cell(32): 11-20, 2008. [Full Text/Abstract]

11. Kautz L, Meynard D, Monnier A, Darnaud V, Bouvet R, Wang RH, Deng C, Vaulont S, Mosser J, Coppin H, Roth MP Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver. Blood(112): 1503-9, 2008. [Full Text/Abstract]

12. Jeker LT, Barthlott T, Keller MP, Zuklys S, Hauri-Hohl M, Deng CX, Hollander GA Maintenance of a normal thymic microenvironment and T cell homeostasis require Smad4-mediated signalling in thymic epithelial cells. Blood, 2008. [Full Text/Abstract]

13. Gautam D, Jeon J, Li JH, Han SJ, Hamdan FF, Cui Y, Lu H, Deng C, Gavrilova O, Wess J Metabolic roles of the M3 muscarinic acetylcholine receptor studied with M3 receptor mutant mice: a review. J Recept Signal Transduct Res(28): 93-108, 2008. [Full Text/Abstract]

14. Tang Y, Kitisin K, Jogunoori W, Li C, Deng CX, Mueller SC, Ressom HW, Rashid A, He AR, Mendelson JS, Jessup JM, Shetty K, Zasloff M, Mishra B, Reddy EP, Johnson L, Mishra L Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling. Proc Natl Acad Sci U S A(105): 2445-50, 2008. [Full Text/Abstract]

15. Mantel CR, Wang RH, Deng C, Broxmeyer HE Sirt1, notch and stem cell "age asymmetry". Cell Cycle(7): 2821-5, 2008. [Full Text/Abstract]

16. Jacobs KM, Pennington JD, Bisht KS, Aykin-Burns N, Kim HS, Mishra M, Sun L, Nguyen P, Ahn BH, Leclerc J, Deng CX, Spitz DR, Gius D SIRT3 interacts with the daf-16 homolog FOXO3a in the mitochondria, as well as increases FOXO3a dependent gene expression. Int J Biol Sci(4): 291-9, 2008. [Full Text/Abstract]

17. Rajagopal R, Dattilo L, Kaartinen V, Deng C, Umans L, Zwijsen A, Roberts A, Bottinger E, Beebe DC The Functions of the type I BMP receptor, Acvr1 (Alk2), in Lens Development: Cell Proliferation, Terminal Differentiation and Survival. Invest Ophthalmol Vis Sci, 2008. [Full Text/Abstract]

18. Li W, Xiao C, Vonderhaar BK, Deng CX A role of estrogen/ERalpha signaling in BRCA1-associated tissue-specific tumor formation. Oncogene, 2007. [Full Text/Abstract]

19. Cao L, Xu X, Cao LL, Wang RH, Coumoul X, Kim SS, Deng CX Absence of full-length Brca1 sensitizes mice to oxidative stress and carcinogen-induced tumorigenesis in the esophagus and forestomach. Carcinogenesis(28): 1401-7, 2007. [Full Text/Abstract]

20. Varticovski L, Hollingshead MG, Robles AI, Wu X, Cherry J, Munroe DJ, Lukes L, Anver MR, Carter JP, Borgel SD, Stotler H, Bonomi CA, Nunez NP, Hursting SD, Qiao W, Deng CX, Green JE, Hunter KW, Merlino G, Steeg PS, Wakefield LM, Barrett JC Accelerated preclinical testing using transplanted tumors from genetically engineered mouse breast cancer models. Clin Cancer Res(13): 2168-77, 2007. [Full Text/Abstract]

21. Li W, Sandhoff R, Kono M, Zerfas P, Hoffmann V, Ding BC, Proia RL, Deng CX Depletion of ceramides with very long chain fatty acids causes defective skin permeability barrier function, and neonatal lethality in ELOVL4 deficient mice. Int J Biol Sci(3): 120-8, 2007. [Full Text/Abstract]

22. Li W, Chen Y, Cameron DJ, Wang C, Karan G, Yang Z, Zhao Y, Pearson E, Chen H, Deng C, Howes K, Zhang K Elovl4 haploinsufficiency does not induce early onset retinal degeneration in mice. Vision Res(47): 714-22, 2007. [Full Text/Abstract]

23. Li H, Watford W, Li C, Parmelee A, Bryant MA, Deng C, O''Shea J, Lee SB Ewing sarcoma gene EWS is essential for meiosis and B lymphocyte development. J Clin Invest(117): 1314-23, 2007. [Full Text/Abstract]

24. Wahl MB, Deng C, Lewandoski M, Pourquié O FGF signaling acts upstream of the NOTCH and WNT signaling pathways to control segmentation clock oscillations in mouse somitogenesis. Development(134): 4033-41, 2007. [Full Text/Abstract]

25. Zhao M, Li D, Shimazu K, Zhou YX, Lu B, Deng CX Fibroblast Growth Factor Receptor-1 Is Required for Long-Term Potentiation, Memory Consolidation, and Neurogenesis. Biol Psychiatry, 2007. [Full Text/Abstract]

26. Tominaga Y, Wang A, Wang RH, Wang X, Cao L, Deng CX Genistein inhibits Brca1 mutant tumor growth through activation of DNA damage checkpoints, cell cycle arrest, and mitotic catastrophe. Cell Death Differ(14): 472-9, 2007. [Full Text/Abstract]

27. Wang X, Liu L, Montagna C, Ried T, Deng CX Haploinsufficiency of Parp1 accelerates Brca1-associated centrosome amplification, telomere shortening, genetic instability, apoptosis, and embryonic lethality. Cell Death Differ, 2007. [Full Text/Abstract]

28. Deng C In celebration of Dr. Mario R. Capecchi''s Nobel Prize. Int J Biol Sci(3): 417-9, 2007. [Full Text/Abstract]

29. Izeradjene K, Combs C, Best M, Gopinathan A, Wagner A, Grady WM, Deng CX, Hruban RH, Adsay NV, Tuveson DA, Hingorani SR Kras(G12D) and Smad4/Dpc4 Haploinsufficiency Cooperate to Induce Mucinous Cystic Neoplasms and Invasive Adenocarcinoma of the Pancreas. Cancer Cell(11): 229-43, 2007. [Full Text/Abstract]

30. Song L, Yan W, Chen X, Deng CX, Wang Q, Jiao K Myocardial smad4 is essential for cardiogenesis in mouse embryos. Circ Res(101): 277-85, 2007. [Full Text/Abstract]

31. Pan D, Schomber T, Kalberer CP, Terracciano LM, Hafen K, Krenger W, Hao-Shen H, Deng C, Skoda RC Normal erythropoiesis but severe polyposis and bleeding anemia in Smad4 deficient mice. Blood, 2007. [Full Text/Abstract]

32. Wang L, Balas B, Christ-Roberts CY, Kim RY, Ramos FJ, Kikani CK, Li C, Deng C, Reyna S, Musi N, Dong LQ, DeFronzo RA, Liu F Peripheral disruption of the Grb10 gene enhances insulin signaling and sensitivity in vivo. Mol Cell Biol(27): 6497-505, 2007. [Full Text/Abstract]

33. Oppermann M, Mizel D, Kim SM, Chen L, Faulhaber-Walter R, Huang Y, Li C, Deng C, Briggs J, Schnermann J, Castrop H Renal function in mice with targeted disruption of the A isoform of the Na-K-2Cl co-transporter. J Am Soc Nephrol(18): 440-8, 2007. [Full Text/Abstract]

34. Shukla V, Coumoul X, Wang RH, Kim HS, Deng CX RNA interference and inhibition of MEK-ERK signaling prevent abnormal skeletal phenotypes in a mouse model of craniosynostosis. Nat Genet, 2007. [Full Text/Abstract]

35. Shukla V, Coumoul X, Deng CX RNAi-based conditional gene knockdown in mice using a U6 promoter driven vector. Int J Biol Sci(3): 91-9, 2007. [Full Text/Abstract]

36. Jia Q, McDill BW, Li SZ, Deng C, Chang CP, Chen F Smad signaling in the neural crest regulates cardiac outflow tract remodeling through cell autonomous and non-cell autonomous effects. Dev Biol(311): 172-84, 2007. [Full Text/Abstract]

37. Anthoni M, Wang G, Deng C, Wolff HJ, Lauerma AI, Alenius HT Smad3 signal transducer regulates skin inflammation and specific IgE response in murine model of atopic dermatitis. J Invest Dermatol(127): 1923-9, 2007. [Full Text/Abstract]

38. Karlsson G, Blank U, Moody JL, Ehinger M, Singbrant S, Deng CX, Karlsson S Smad4 is critical for self-renewal of hematopoietic stem cells. J Exp Med(204): 467-74, 2007. [Full Text/Abstract]

39. Ko SO, Chung IH, Xu X, Oka S, Zhao H, Cho ES, Deng C, Chai Y Smad4 is required to regulate the fate of cranial neural crest cells. Dev Biol(312): 435-47, 2007. [Full Text/Abstract]

40. Niwa Y, Masamizu Y, Liu T, Nakayama R, Deng CX, Kageyama R The initiation and propagation of hes7 oscillation are cooperatively regulated by fgf and notch signaling in the somite segmentation clock. Dev Cell(13): 298-304, 2007. [Full Text/Abstract]

41. Xiao C, Sharp JA, Kawahara M, Davalos AR, Difilippantonio MJ, Hu Y, Li W, Cao L, Buetow K, Ried T, Chadwick BP, Deng CX, Panning B The XIST Noncoding RNA Functions Independently of BRCA1 in X Inactivation. Cell(128): 977-89, 2007. [Full Text/Abstract]

42. Gautam D, Han SJ, Hamdan FF, Jeon J, Li B, Li JH, Cui Y, Mears D, Lu H, Deng C, Heard T, Wess J A critical role for beta cell M3 muscarinic acetylcholine receptors in regulating insulin release and blood glucose homeostasis in vivo. Cell Metab (3): 449-61, 2006. [Full Text/Abstract]

43. Shukla V, Coumoul X, Cao L, Wang RH, Xiao C, Xu X, Ando S, Yakar S, Leroith D, Deng C Absence of the full-length breast cancer-associated gene-1 leads to increased expression of insulin-like growth factor signaling axis members. Cancer Res (66): 7151-7, 2006. [Full Text/Abstract]

44. Cao L, Kim S, Xiao C, Wang RH, Coumoul X, Wang X, Li WM, Xu XL, De Soto JA, Takai H, Mai S, Elledge SJ, Motoyama N, Deng CX ATM-Chk2-p53 activation prevents tumorigenesis at an expense of organ homeostasis upon Brca1 deficiency. EMBO J (25): 2167-77, 2006. [Full Text/Abstract]

45. Park C, Lavine K, Mishina Y, Deng CX, Ornitz DM, Choi K Bone morphogenetic protein receptor 1A signaling is dispensable for hematopoietic development but essential for vessel and atrioventricular endocardial cushion formation. Development , 2006. [Full Text/Abstract]

46. Deng CX BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution. Nucleic Acids Res (34): 1416-26, 2006. [Full Text/Abstract]

47. Wang W, Huang XR, Canlas E, Oka K, Truong LD, Deng C, Bhowmick NA, Ju W, Bottinger EP, Lan HY Essential role of Smad3 in angiotensin II-induced vascular fibrosis. Circ Res (98): 1032-9, 2006. [Full Text/Abstract]

48. Smolen GA, Muir B, Mohapatra G, Barmettler A, Kim WJ, Rivera MN, Haserlat SM, Okimoto RA, Kwak E, Dahiya S, Garber JE, Bell DW, Sgroi DC, Chin L, Deng CX, Haber DA Frequent met oncogene amplification in a Brca1/Trp53 mouse model of mammary tumorigenesis. Cancer Res (66): 3452-5, 2006. [Full Text/Abstract]

49. Israelsson C, Lewen A, Kylberg A, Usoskin D, Althini S, Lindeberg J, Deng CX, Fukuda T, Wang Y, Kaartinen V, Mishina Y, Hillered L, Ebendal T Genetically modified bone morphogenetic protein signalling Alters traumatic brain injury-induced gene expression responses in the adult mouse. J Neurosci Res (84): 47-57, 2006. [Full Text/Abstract]

50. Kim SS, Cao L, Lim SC, Li C, Wang RH, Xu X, Bachelier R, Deng CX Hyperplasia and Spontaneous Tumor Development in the Gynecologic System in Mice Lacking the BRCA1-{Delta}11 Isoform. Mol Cell Biol (26): 6983-92, 2006. [Full Text/Abstract]

Page last updated: December 15, 2008

General inquiries may be addressed to: Office of Communications & Public Liaison
Building 31. Rm 9A06
31 Center Drive, MSC 2560
Bethesda, MD 20892-2560
For information about NIDDK programs: 301.496.3583

The National Institutes of Health   Department of Health and Human Services is the U.S. government's official web portal to all federal, state, and local government web resources and services.  HONcode Seal - Link to the Health on the Net Foundation