中文版
 

Jianhua Yang

Jianhua Yang, Ph.D.

Associate Professor

Texas Children’s Cancer Center

Department of Pediatrics

Baylor College of Medicine

Houston, Texas 77030

Voice: 832-824-4572

Fax: 832-825-4732

Email:jianhuay@bcm.edu

 

EDUCATION AND TRAINING:

2000-2002                  Department of Immunology, Baylor College of Medicine, Houston, TX

         Postdoc in Dr. David Roth’s laboratory

        * DNA damage response and V(D)J recombination

1994-2000               Department of Immunology, MD Anderson Cancer Center, University of Texas-

                             Houston,Houston, TX

                             Ph.D. in Dr. Bing Su’s laboratory

                             *MAP kinase signaling

1990-1993           Department of Biology, Harbin Medical University, Harbin, P. R. China

                             M.S. in Dr. Guiyin Zhang’s laboratory

                            *Cytogenetic and biochemical diagnosis of human inherited disease

1983-1987              Department of Biology, Xinjiang University, Urumqi, P. R. China

        B.S. in biology

 

EXPERIENCE:

2012-present        Associate Professor, Texas Children’s Cancer Center, Department of Pediatrics,

                             Baylor College of Medicine, Houston, TX

2002-2012            Assistant Professor, Texas Children’s Cancer Center, Department of Pediatrics,

                             Baylor College of Medicine, Houston, TX

2002-2002                        Research Scientist, Tanox Biotechnology Inc., Houston TX

1987-1990            Research Assistant, Yining Medical School, Yining, P. R. China

 

AWARDS AND HONORS:

1997                    University of Texas-Houston, GSBS, John P. McGovern Award

2002                    The Leukemia & Lymphoma Society Postdoctoral Fellowship Award

2002                    American Cancer Society Postdoctoral Fellowship Award

 

FUNDING:

Ongoing

 

NIH-NINDS   R01  1R01NS072420-01    Yang  (PI)            03/01/11 – 02/31/15   

DUSP26: A Novel Therapeutic Target in Neuroblastoma  $218,750/$875,000

Major Goals of Project is: 1) to determine the role of DUSP26 in neuroblastoma development and chemoresistance in xenograft mouse models; 2) to determine the efficacy of DUSP26 small molecule inhibitor in the inhibition of neuroblastoma development in xenograft mouse model.

 

Role: PI

 

CPRIT: RP110187   Nuchtern (PI)     10/29/2010 – 09/31/12

Neuroblastoma-Derived Secretory Protein Receptor, a New Target for Neuroblastoma Therapy

$167,699/ $335,398

Major Goals of Project is: 1) to determine the role of NDSP in neuroblastoma development; 2) to identify and clone potential NDSP receptor in neurobloastoma.

 

Role: Co-Investigator

           

Completed

 

Dan Duncan Cancer Center Pilot Project  Yang (PI)

Ubiquitination Control of MYCN Oncogenic Activity in Neuroblastoma     $60,000   01/01/10-12/31/10

Major Goal of Project is to identify the deubiquitinase that control MYCN oncogenic activity in neuroblastoma.

Role: PI

 

The American Cancer Society   RSG-06-070-01-TBE      Yang  (PI)      01/01/06 – 12/31/10   

Analysis of a Neuroblastoma Specific Phosphatase             $149,167/$599,427

Major Goals of Project: 1) To determine the significance of NSP expression in neuroblastoma tumor progression, 2) To determine whether NSP is involved in regulating neuroblastoma proliferation and metastasis, and 3) To determine the function of NSP in regulating intracellular signaling cascades in neuroblastoma.

Role: PI

 

BCM Seed Fund     Yang (PI)                                                   01/03-12/03

Analysis of Deregulated Signaling Pathways in Neuroblastoma           $25,000

Major Goal of Project: To determine the role of MAPK signaling in neuroblastoma proliferation.

Role: PI

                                  

BCM Cancer Center     Yang  (PI)                                               07/01/04-06/30/06     

Analysis of a Novel Biomarker in High-Risk Neuroblastoma                        $30,000

Major Goal of Project: To determine whether NDSP is a novel biomarker for neuroblastoma prognosis and diagnosis.

Role: PI

Bear Necessities Pediatric Cancer Foundation       Yang  (PI)         09/01/04-08/31/06             

Characterization of a Novel Neuroblastoma Specific Phosphatase              $80,000

Major Goals of Project:To determine the NSP expression in neuroblastoma cell lines and tumor samples.

Role: PI

 

BCM Breast Center       Yang  (PI)                                                         12/01/04-11/30/05      

Significance of MEKK3 Amplification in Breast Carcinoma            $25,000

Major Goals of Project:  1) to test whether MEKK3 is required for breast cancer chemo-resistance,  2) to test whether MEKK3 is required for breast cancer progression in vitroand in vivo, and 3) to test whether MEKK3 is required for cellular oncogenic transformation in vitro.

Role: PI

 

Hope Street Kids      Yang  (PI)                               07/01/05-06/30/07  

The Role of a Novel Phosphatase in Neuroblastoma Progression                $35,000/$70,000

The major goal of this project is to determine whether NSP is involved in regulating neuroblastoma development.

Role: PI

 

NIH-NCI   R21 1R21CA106513-01A2  Yang  (PI)                           

Analysis of a Novel Secreted Protein in Neuroblastoma              $86,000 / $172,000   07/01/05 – 08/30/07                                                                                            

Major Goals of Project:  1) To determine whether NDSP is a potential biomarker for neuroblastoma; and 2) to determine whether NDSP is involved in regulating meuroblastoma tumor formation and dissemination.

Role: PI

 

Duncan Inter-Institutional Pilot Project (PI)

Fullerene Peptides in the Treatment of Neuroblastoma         $70,000   01/01/08-12/31/08

Major Goals of Project is to establish the fullerene peptides as a type of therapeutic agent to cure neuroblstoma.

Role: PI

 

Virginia and L. E.  Simmons Foundation Collaborative Project (PI)

Fullerene Peptides in the Treatment of Neuroblastoma         $46,500   01/01/09-12/31/09

Major Goals of Project is to establish the fullerene peptides as a type of therapeutic agent to cure neuroblstoma.

Role: PI

 

PUBLICATIONS:

 

1.    Yang J,  New L, Jiang Y, Han J, Su B. (1998) Molecular cloning and characterization of a human protein kinase that specifically activates c-Jun N- terminal kinase. Gene 212: 95-102. PMID: 9661668.

2.    Lee L, Jiang F, Nicosia SV, Yang J, Su B, Bai W. (2000) MEKK1 activating human estrogen receptor    alpha and stimulation of the agonistic activity of 4-hydoxytamoxifen in endometrial and ovarian cancer cells. Mol Endocrinol.  14:1882-1896. PMID: 11075819.

3.    Xia Y, Makris C, Su B, Li E, Yang J, Nemerow GR, Karin M. (2000) MEK kinase 1 is critically required for c-Jun N-terminal kinase activation by proinflammatory stimuli and growth factor-induced cell migration. Proc Natl Acad Sci U S A 97: 5243-5248. PMID: 10805784.

4.    Yang J, Cheng J,  Xia Y, Karin M,  Su B. (2000) Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation. Mol Cell Biol. 20: 2334-2342. PMID: 10713157.

5.    Yang J, Boerm M, McCarty M, Bucana C, Fidler IJ, Zhang Y, Su B. (2000) Mekk3 is essential for early embryonic cardiovascular development. Nature Genetics  24: 309-313. PMID: 10700190.

6.    Su B, Cheng J, Yang J, Guo Z. (2001) MEKK2 is required for T-cell receptor signals in JNK activation and Interleukin-2 gene expression. J Biol Chem.276: 14784-14790. PMID: 11278622.

7.    Yang J, Lin Y, Guo Z, Cheng J, Huang J, Deng L, Liao W, Chen Z, Liu Z, Su B. (2001) The essential role of MEKK3 in TNF-induced NF-kappaB activation. Nature Immunology  2: 620-624. PMID: 11429546.

8.    Yang J, Hu G, Wang S, Li Y, Martin R, Li K, Yao Z.  (2003) Calcineurin/Nuclear Factors of Activated T cells (NFAT)-activating and Immunoreceptor Tyrosine-based Activation Motif (ITAM)-containing protein that activates Calcineurin/NFAT signaling pathway. J Biol Chem.  278: 16797-16801. PMID: 12615919.

9.    Huang Q, Yang J, Lin Y, Walker C, Cheng J, Liu ZG, Su B. (2004) Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3. Nature Immunology 5: 98-103. PMID: 14661019.

10.  Vasudevan SA, Skoko J, Wang K, Burlingame SM, Patel PN, Lazo JS, NuchternJG, Yang J*. (2005)  MKP- 8, a novel MAPK phosphatase that inhibits p38 kinase. Biochem Biophys Res Commun330: 511-518. PMID: 15796912.

11.  Abbasi S, Su B, Kellems RE, Yang J, Xia Y. (2005) The essential role of MEKK3 signaling in angiotensin-II-induced calcineurin/NFAT activation. J Biol Chem.280: 36737-36746. PMID: 16126726.

12.  Abbasi S, Lee JD, Su B, Chang X, Alcon J, Yang J, Kellems RE, Xia Y. (2006) Protein kinase mediated regulation of calcineurin through the phosphorylation of modulatory calcineurin interacting protein 1. J Biol Chem. 281: 7717-7726. PMID: 16415348.

13.  Deng M, Chen WL, Takatori A, Peng Z, Zhang L, Mongan M, Parthasarathy R, Sartor M, Miller M, Yang J, Su B, Kao WW, Xia Y. (2006) A role for the mitogen-activated protein kinase kinase kinase 1 in epithelial wound healing. Mol Biol Cell. 8: 3446-3455. PMID: 16760432.

14.  Yang J, Wang K, Driver J, Yang J and Barron AR. (2007) The use of fullerene substituted

       phenylalanine amino acid as a passport for peptides through cell membranes. Org. Biomol.

      Chem. 5: 260-266.PMID: 17205169.

15.  Vasudevan SA, Russell HV, Okcu MF, Burlingame SM, Liu ZJ, Yang J*, Nuchtern JG*.

       (2007) Neuroblastoma-derived secretory protein messenger RNA levels correlate with high-risk

       neuroblastoma.J  Pediatr Surg. 42:148-152. PMID: 17208556.

16.  Deng Y, Yang J, McCarty M, Su B. (2007)MEKK3 is required for endothelium function but is

       not essential for tumor growth and angiogenesis. Am J Physiol Cell Physiol.293:C1404-1411. 

      PMID: 17687003.

17.  Shu Q, Wong KK, Su JM, Adesina AM, Yu LT, Tsang YT, Antalffy BC, Baxter P, Perlaky L,    

      Yang J, Dauser RC, Chintagumpala M, Blaney SM, Lau CC, Li XN. (2008) Direct orthotopic  

      transplantation of fresh surgical specimen preserves CD133+ tumor cells in clinically relevant

       mouse models of medulloblastoma and glioma. Stem Cells.26:1414-1424. PMID: 18403755.

18.  Yu Y, Ge N, Xie M, Sun W, Burlingame S, Pass AK, Nuchtern JG, Zhang D, Fu S, Schneider

      MD, Fan J, Yang J*. (2008) Phosphorylation of Thr-178 and Thr-184 in the TAK1 T-loop is

       required for interleukin (IL)-1-mediated optimal NFkappaB and AP-1 activation as well as IL-6

       gene expression.J Biol Chem. 283: 24497-24505. PMID: 18617512.

19.  Sun W, Yu Y, Dotti G, Shen T, Tan X, Savoldo B, Pass AK, Chu M, Zhang D, Lu X, Fu S, Lin X,

      Yang J*.(2009) PPM1A and PPM1B act as IKKβ phosphatases to terminate TNFα-induced

      IKKβ-NF-κB activation. Cell Signal.  21:95-102. PMID: 18930133.

20.  Sun W, Li H, Yu Y, Fan Y, Grabiner BC, Mao R, Ge N, Zhang H, Fu S, Lin X, Yang J*.(2009)

       MEKK3 is required for lysophosphatidic acid-induced NF-kappaB activation. Cell Signal. 

      21:1488-1494. PMID: 19465115.

21.  Shi Z, Cai Z, Wen S, Chen C, Gendron C, Sanchez A, Patterson K, Fu S, Yang J, Wildman  

       DE, Finnell RH, Zhang D. (2009) Transcriptional regulation of the novel toll-like receptor

       TLR13. J Biol Chem. 284:20540-20547. PMID: 19487701.

22.  Shang X, Burlingame SM, Okcu MF, Ge N, Russell HV, Egler RA, David RD, Vasudevan SA,

      Yang J, Nuchtern JG. (2009) Aurora A is a negative prognostic factor and a new therapeutic

      target in human neuroblastoma. Mol Cancer Ther. 8: 2461-2469. PMID: 19671766.

23.  Vasudevan SA, Shang X, Chang S, Ge N, Diaz-Miron JL, Russell HV, Hicks MJ, Ludwig AD,

       Wesson CL, Burlingame SM, Kim ES, Khan J, Yang J*, Nuchtern JG*. (2009) Neuroblastoma-

       derived secretory protein is a novel secreted factor overexpressed in neuroblastoma.Mol

      Cancer Ther.8: 2478-2489. PMID: 19671756.

24.  Fan Y, Mao R, Zhao Y, Yu Y, Sun W, Song P, Shi Z, Zhang D, Yvon E, Zhang H, Fu S, Yang

       J*.(2009) Tumor necrosis factor-alpha induces RelA degradation via ubiquitination at lysine

      195 to prevent excessive nuclear factor-kappaB activation. J Biol Chem.  284: 29290-29297.

      PMID: 19706600.

25.  Zhang X, Lin L, Guo H, Yang J, Jones SN, Jochemsen A, Lu X. (2009) Phosphorylation and 

       degradation of MdmX is inhibited by Wip1 phosphatase in the DNA damage response. Cancer

       Research. 69: 7960-7968. PMID: 19808970.

26.  Cai Z, Shi Z, Sanchez A, Zhang T, Liu M, Yang J, Wang F, Zhang D. (2009) Transcriptional  

       regulation of TLR11 gene expression in epithelial cells. J Biol Chem.284:33088-33096. PMID:

       19801549.

27.  Sun W, Tan X, Shi Y, Xu G, Mao R, Gu X, Fan Y, Yu Y, Burlingame S, Zhang H, Rednam SP,

       Lu X, Zhang T, Fu S, Cao G, Qin J, Yang J*. (2010) USP11 negatively regulates TNFalpha-

       induced NF-kappaB activation by targeting on IkappaBalpha. Cell Signal.22: 386-394. PMID:

       19874889.

28.  Xu G, Tan X, Wang H, Sun W, Shi Y, Burlingame S, Gu X, Cao G, Zhang T, Qin J, Yang J*.

       (2010) Ubiquitin specific peptidase 21 inhibits tumor necrosis factor alpha-induced nuclear  

       factor-kappaB activation via binding to and deubiquitinating receptor-interacting protein 1. J Biol

      Chem.285: 969-978. PMID: 19910467.

29.  Fan Y, Yu Y, Shi Y, Sun W, Xie M, Ge N, Mao R, Zhang A, Xu G, Schneider MD, Zhang H, Fu  

      S, Qin J, Yang J*. (2010) Lysine 63-linked polyubiquitination of TAK1 at lysine 158 is required

       for tumor necrosis factor alpha- and interleukin-1 beta-induced IKK/NF-kappaB and JNK/AP-1

       activation. J Biol Chem. 285: 5347-5360. PMID: 20038579.

30.  Sun W, Ge N, Yu Y, Burlingame S, Li X, Zhang M, Ye S, Fu S, Yang J*. (2010) Phosphorylation

       of Thr-516 and Ser-520 in the kinase activation loop of MEKK3 is required for lysophosphatidic

       acid-mediated optimal IkappaB kinase beta (IKKbeta)/nuclear factor-kappaB (NF-kappaB)

       activation. J Biol Chem. 285:7911-7918. PMID:20068038.

31.  Sun W, Wang H, Zhao X, Yu Y, Fan Y, Wang H, Wang X, Lu X, Zhang G, Fu S, Yang J*. (2010)

       Protein phosphatase 2A acts as a mitogen-activated protein kinase kinase kinase 3 (MEKK3)

       phosphatase to inhibit lysophosphatidic acid-induced IkappaB kinase beta/nuclear factor-kappaB

       activation. J Biol Chem.285: 21341-21348. PMID: 20448038.

32.  Sun W, Yang J* (2010) Molecular basis of lysophosphatidic acid-Induced NF-kappaB activation.

      Cell Signal. 22: 1799-1803. PMID: 20471472.

33.  Shang X, Vasudevana SA, Yu Y, Ge N, Ludwig AD, Wang K, Burlingame S, Zhao YJ, Rao PH,  

       Lu X, Russell HV, Okcu MF, Hicks MJ, Shohet JM, Donehower LA, Nuchtern JG*and Yang

       J*. (2010) Dual-specificity phosphatase 26 is a novel p53 phosphatase and inhibits p53 tumor

      suppressor functions in human neuroblastoma. Oncogene.29: 4938-4946.  PMID: 20562916.

34.  Mao R, Fan Y, Mou Y, Zhang H, Fu S, Yang J*. (2011) TAK1 lysine 158 is required for TGF-β-

       induced TRAF6-mediated Smad-independent IKK/NF-κB and JNK/AP-1 activation.Cell Signal.

       23: 222-227. PMID: 20837137.

35.  Shi Z, Cai Z, Sanchez A, Zhang T, Wen S, Wang J, Yang J, Fu S, Zhang D. (2011) A novel

       toll-like receptor that recognizes vesicular stomatitis virus. J Biol Chem. 286:4517-4524.  

       PMID: 21131352.

36.  Fan Y, Yu Y, Mao R, Zhang H, Yang J*. (2011) TAK1 Lys-158 but not Lys-209 is required for

       IL-1β-induced Lys63-linked TAK1 polyubiquitination and IKK/NF-κB activation. Cell Signal. 23:  

       660-665. PMID: 21130870.

37.  Yu L, Baxter PA, Zhao X, Liu Z, Wadhwa L, Zhang Y, Su JM, Tan X, Yang J, Adesina A,

       Perlaky L, Hurwitz M, Idamakanti N, Police SR, Hallenbeck PL, Blaney SM, Chintagumpala M,

       Hurwitz RL, Li XN. (2011) A single intravenous injection of oncolytic picornavirus SVV-001

       eliminates medulloblastomas in primary tumor-based orthotopic xenograft mouse models.  

       Neuro Oncol. 13: 14-27. PMID: 21075780.

38.  Fan YH, Yu Y, Mao RF, Tan XJ, Xu GF, Zhang H, Lu XB, Fu SB, Yang J*. (2011) USP4

       targets TAK1 to downregulate TNFalpha-induced NF-kappaB activation. Cell Death Differ.

       18: 1547-1560. PMID: 21331078.

 

39.  Zhang X, Berger FG, Yang J, Lu X. (2011) USP4 inhibits p53 through deubiquitinating and

       stabilizing ARF-BP1. EMBO J. 30: 2177-2189. PMID:21522127.

40.  Fan Y, Shi Y, Liu S, Mao R, An L, Zhao Y, Zhang H, Zhang F, Xu G, Qin J, Yang J*. (2012)

       Lys48-linked TAK1 polyubiquitination at lysine-72 downregulates TNFα-induced NF-κB activation

       via mediating TAK1 degradation. Cell Signal. 24:1381-1389. PMID:22406003.

41.  Zhao Y, Liang L, Fan Y, Sun S, An L, Shi Z, Cheng J, Jia W, Sun W, Mori-Akiyama Y, Zhang H,

       Fu S, Yang J*. (2012) PPM1B negatively regulates antiviral response via dephosphorylating

       TBK1. Cell Signal. 24: 2197–2204. PMID: 22750291.

42.  Liang L, Fan Y, Cheng J, Cheng D, Zhao Y, Cao B, Ma L, An L, Jia W, Su X, Yang J*, Zhang H*.

       (2012) TAK1 ubiquitination regulates doxorubicin-induced NF-κB activation.Cell Signal. 25: 247-

       254. PMID: 22981905.

43.  Ernst A, Avvakumov G, Tong J, Fan Y, Zhao Y, Alberts P, Persaud A, Walker JR, Neculai AM,

       Neculai D, Vorobyov A, Garg P, Beatty L, Chan PK, Juang YC, Landry MC, Yeh C, Zeqiraj E,

       Karamboulas K, Allali-Hassani A, Vedadi M, Tyers M, Moffat J, Sicheri F, Pelletier L, Durocher D,

       Raught B, Rotin D, Yang J, Moran MF, Dhe-Paganon S, Sidhu SS. (2013) A Strategy for

       Modulation of Enzymes in the Ubiquitin System. Science339:590-595. PMID: 23287719.

44.   Fan Y, Cheng J, Vasudevan SA, Patel RH, Liang L, Xu X, Zhao Y, Jia W, Lu F, Zhang H,

Nuchtern JG, Kim ES, Yang J*.2013TAK1 inhibitor 5Z-7-oxozeaenol sensitizes neuroblastoma to chemotherapy. Apoptosis. 2013 May 23. [Epub ahead of print].

 

      

* Corresponding author (21 papers).

 

Invited talk at meeting

 

AACR-NCI-EORTC international conference on molecular targets and cancer therapeutics, Hynes Center, Boston, MA, Nov 17-21, 2003.

 

Identification of molecular targets in neuroblastoma, Translational Genomics in Neuroblastoma, Gaithersberg, MD, Oct. 16-18, 2005

 

Overexpression of MKP-8 contributes to chemoresistance in human neuroblastoma cells, Harry and Elsa Jiler-American Cancer Society Professors Meeting, Nov 8-11, 2007.

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