Keywords
Last Name

Zhijun Luo, MD, PhD

TitleAssociate Professor
InstitutionBoston University School of Medicine
DepartmentBiochemistry
Address75 E. Newton St Evans Building
Boston MA 02118
Phone(617) 414-1033
ORCID ORCID Icon0000-0003-3509-4046
Other Positions
TitleGraduate Faculty (Primary Mentor of Grad Students)
InstitutionBoston University School of Medicine, Division of Graduate Medical Sciences

InstitutionBoston Medical Center

 Research Expertise & Professional Interests
Research Interests: Regulation of tumor cell growth and metabolism by protein phosphorylation

The overall research interest in my laboratory is to understand how protein phosphorylation regulates cell growth and metabolism, and how its alteration causes diseases such as cancer and metabolic disorders. Our ongoing research focuses on characterization of AMP-activated protein kinase and Raf kinase, both of which have been implicated in cancer and other disorders.

AMPK serves as a fuel-sensing enzyme that is activated by binding of 5’ AMP to the? gamma subunit and phosphorylation of the catalytic subunit at Thr 172 by upstream kinases such as LKB1 and CaMKK. The activation of AMPK has been shown to improve metabolic syndrome and to be implicated in control of cancer cell growth. One of our research interests is to test the hypothesis that AMPK functions as a metabolic tumor suppressor. Using microarray and proteomic approaches, we have identified several target molecules regulated by AMPK and are currently evaluating their functional relationship with AMPK and biological relevance.

Raf kinases, consisting of three isoforms, Raf-1, B-Raf and A-Raf, act as immediate downstream effectors of Ras. They are implicated in tumorigenesis, inasmuch as activating mutations of the ras genes have been found in 20-30% of overall human cancers and activated mutants of B-Raf frequently reported in human cancers. Although the linear relationship of the Ras/Raf/MEK/Erk signaling pathway has been delineated, the mechanism of Raf activation still remains elusive. We have a long standing interest in characterizing phosphorylation of Raf for its activation, and identifying kinases responsible for these phosphorylation events and downstream targets in addition to MEK1/2.

 Publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. He H, Liu D, Lin H, Jiang S, Ying Y, Chun S, Deng H, Zaia J, Wen R, Luo Z. Phosphatidylethanolamine binding protein 4 (PEBP4) is a secreted protein and has multiple functions. Biochim Biophys Acta. 2016 Jul; 1863(7 Pt A):1682-9. PMID: 27033522.
    View in: PubMed
  2. Huang D, He X, Zou J, Guo P, Jiang S, Lv N, Alekseyev Y, Luo L, Luo Z. Negative regulation of Bmi-1 by AMPK and implication in cancer progression. Oncotarget. 2016 Feb 2; 7(5):6188-200. PMID: 26717043.
    View in: PubMed
  3. Li NS, Zou JR, Lin H, Ke R, He XL, Xiao L, Huang D, Luo L, Lv N, Luo Z. LKB1/AMPK inhibits TGF-ß1 production and the TGF-ß signaling pathway in breast cancer cells. Tumour Biol. 2016 Jun; 37(6):8249-58. PMID: 26718214.
    View in: PubMed
  4. Yang Z, Xie C, Xu W, Liu G, Cao X, Li W, Chen J, Zhu Y, Luo S, Luo Z, Lu N. Phosphorylation and inactivation of PTEN at residues Ser380/Thr382/383 induced by Helicobacter pylori promotes gastric epithelial cell survival through PI3K/Akt pathway. Oncotarget. 2015 Oct 13; 6(31):31916-26. PMID: 26376616.
    View in: PubMed
  5. Lin H, Li N, He H, Ying Y, Sunkara S, Luo L, Lv N, Huang D, Luo Z. AMPK Inhibits the Stimulatory Effects of TGF-ß on Smad2/3 Activity, Cell Migration, and Epithelial-to-Mesenchymal Transition. Mol Pharmacol. 2015 Dec; 88(6):1062-71. PMID: 26424816.
    View in: PubMed
  6. Luo L, Jiang S, Huang D, Lu N, Luo Z. MLK3 phophorylates AMPK independently of LKB1. PLoS One. 2015; 10(4):e0123927. PMID: 25874865.
    View in: PubMed
  7. He H, Ke R, Lin H, Ying Y, Liu D, Luo Z. Metformin, an old drug, brings a new era to cancer therapy. Cancer J. 2015 Mar-Apr; 21(2):70-4. PMID: 25815846.
    View in: PubMed
  8. He G, Zhang YW, Lee JH, Zeng SX, Wang YV, Luo Z, Dong XC, Viollet B, Wahl GM, Lu H. AMP-activated protein kinase induces p53 by phosphorylating MDMX and inhibiting its activity. Mol Cell Biol. 2014 Jan; 34(2):148-57. PMID: 24190973.
    View in: PubMed
  9. Luo L, Huang W, Tao R, Hu N, Xiao ZX, Luo Z. ATM and LKB1 dependent activation of AMPK sensitizes cancer cells to etoposide-induced apoptosis. Cancer Lett. 2013 Jan 1; 328(1):114-9. PMID: 22960274.
    View in: PubMed
  10. Wang B, Zhang H, Zhu M, Luo Z, Peng Y. MEK1-ERKs signal cascade is required for the replication of Enterovirus 71 (EV71). Antiviral Res. 2012 Jan; 93(1):110-7. PMID: 22101247.
    View in: PubMed
  11. Chakrabarti P, English T, Karki S, Qiang L, Tao R, Kim J, Luo Z, Farmer SR, Kandror KV. SIRT1 controls lipolysis in adipocytes via FOXO1-mediated expression of ATGL. J Lipid Res. 2011 Sep; 52(9):1693-701. PMID: 21743036.
    View in: PubMed
  12. Zhou J, Yang Z, Tsuji T, Gong J, Xie J, Chen C, Li W, Amar S, Luo Z. LITAF and TNFSF15, two downstream targets of AMPK, exert inhibitory effects on tumor growth. Oncogene. 2011; 30(16):1892-900.
    View in: External Website
  13. Li Y, Xu S, Mihaylova MM, Zheng B, Hou X, Jiang B, Park O, Luo Z, Lefai E, Shyy JY, Gao B, Wierzbicki M, Verbeuren TJ, Shaw RJ, Cohen RA, Zang M. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 2011 Apr 6; 13(4):376-88. PMID: 21459323.
    View in: PubMed
  14. Li Y, Xu S, Giles A, Nakamura K, Lee JW, Hou X, Donmez G, Li J, Luo Z, Walsh K, Guarente L, Zang M. Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver. FASEB J. 2011 May; 25(5):1664-79. PMID: 21321189.
    View in: PubMed
  15. Li W, Zhou J, Chen L, Luo Z, Zhao Y. Lysyl oxidase, a critical intra- and extra-cellular target in the lung for cigarette smoke pathogenesis. Int J Environ Res Public Health. 2011 Jan; 8(1):161-84. PMID: 21318022.
    View in: PubMed
  16. Zhou J, Yang Z, Tsuji T, Gong J, Xie J, Chen C, Li W, Amar S, Luo Z. LITAF and TNFSF15, two downstream targets of AMPK, exert inhibitory effects on tumor growth. Oncogene. 2011 Apr 21; 30(16):1892-900. PMID: 21217782.
    View in: PubMed
  17. Luo Z, Zang M, Guo W. AMPK as a metabolic tumor suppressor: control of metabolism and cell growth. Future Oncol. 2010 Mar; 6(3):457-70. PMID: 20222801.
    View in: PubMed
  18. Zhang H, Feng H, Luo L, Zhou Q, Luo Z, Peng Y. Distinct effects of knocking down MEK1 and MEK2 on replication of herpes simplex virus type 2. Virus Res. 2010 Jun; 150(1-2):22-7. PMID: 20172001.
    View in: PubMed
  19. Tao R, Gong J, Luo X, Zang M, Guo W, Wen R, Luo Z. AMPK exerts dual regulatory effects on the PI3K pathway. J Mol Signal. 2010; 5(1):1. PMID: 20167101.
    View in: PubMed
  20. Ma T, Zhao Y, Kwak YD, Yang Z, Thompson R, Luo Z, Xu H, Liao FF. Statin's excitoprotection is mediated by sAPP and the subsequent attenuation of calpain-induced truncation events, likely via rho-ROCK signaling. J Neurosci. 2009 Sep 9; 29(36):11226-36. PMID: 19741129.
    View in: PubMed
  21. Zhou J, Huang W, Tao R, Ibaragi S, Lan F, Ido Y, Wu X, Alekseyev YO, Lenburg ME, Hu GF, Luo Z. Inactivation of AMPK alters gene expression and promotes growth of prostate cancer cells. Oncogene. 2009 May 7; 28(18):1993-2002. PMID: 19347029.
    View in: PubMed
  22. Chen Y, Zhou K, Wang R, Liu Y, Kwak YD, Ma T, Thompson RC, Zhao Y, Smith L, Gasparini L, Luo Z, Xu H, Liao FF. Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription. Proc Natl Acad Sci U S A. 2009 Mar 10; 106(10):3907-12. PMID: 19237574.
    View in: PubMed
  23. Zang M, Gong J, Luo L, Zhou J, Xiang X, Huang W, Huang Q, Luo X, Olbrot M, Peng Y, Chen C, Luo Z. Characterization of Ser338 phosphorylation for Raf-1 activation. J Biol Chem. 2008 Nov 14; 283(46):31429-37. PMID: 18775988.
    View in: PubMed
  24. Chakrabarti P, Anno T, Manning BD, Luo Z, Kandror KV. The mammalian target of rapamycin complex 1 regulates leptin biosynthesis in adipocytes at the level of translation: the role of the 5'-untranslated region in the expression of leptin messenger ribonucleic acid. Mol Endocrinol. 2008 Oct; 22(10):2260-7. PMID: 18653778.
    View in: PubMed
  25. Wang L, Persons KS, Jamieson D, Flanagan JN, Hsu HH, Holick MF, Luo Z, Sakaki T, Urushino N, Faller DV, Chen TC. Prostate 25-hydroxyvitamin D-1alpha-hydroxylase is up-regulated by suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor. Anticancer Res. 2008 Jul-Aug; 28(4A):2009-13. PMID: 18649740.
    View in: PubMed
  26. Guo W, Wong S, Xie W, Lei T, Luo Z. Palmitate modulates intracellular signaling, induces endoplasmic reticulum stress, and causes apoptosis in mouse 3T3-L1 and rat primary preadipocytes. Am J Physiol Endocrinol Metab. 2007 Aug; 293(2):E576-86. PMID: 17519282.
    View in: PubMed
  27. Ruderman NB, Keller C, Richard AM, Saha AK, Luo Z, Xiang X, Giralt M, Ritov VB, Menshikova EV, Kelley DE, Hidalgo J, Pedersen BK, Kelly M. Interleukin-6 regulation of AMP-activated protein kinase. Potential role in the systemic response to exercise and prevention of the metabolic syndrome. Diabetes. 2006 Dec; 55 Suppl 2:S48-54. PMID: 17130644.
    View in: PubMed
  28. Park S, Rath O, Beach S, Xiang X, Kelly SM, Luo Z, Kolch W, Yeung KC. Regulation of RKIP binding to the N-region of the Raf-1 kinase. FEBS Lett. 2006 Nov 27; 580(27):6405-12. PMID: 17097642.
    View in: PubMed
  29. Saha AK, Persons K, Safer JD, Luo Z, Holick MF, Ruderman NB. AMPK regulation of the growth of cultured human keratinocytes. Biochem Biophys Res Commun. 2006 Oct 20; 349(2):519-24. PMID: 16949049.
    View in: PubMed
  30. He M, Zhang J, Shao L, Huang Q, Chen J, Chen H, Chen X, Liu D, Luo Z. Upregulation of 14-3-3 isoforms in acute rat myocardial injuries induced by burn and lipopolysaccharide. Clin Exp Pharmacol Physiol. 2006 Apr; 33(4):374-80. PMID: 16620304.
    View in: PubMed
  31. Chadee DN, Xu D, Hung G, Andalibi A, Lim DJ, Luo Z, Gutmann DH, Kyriakis JM. Mixed-lineage kinase 3 regulates B-Raf through maintenance of the B-Raf/Raf-1 complex and inhibition by the NF2 tumor suppressor protein. Proc Natl Acad Sci U S A. 2006 Mar 21; 103(12):4463-8. PMID: 16537381.
    View in: PubMed
  32. Jin Y, Dai MS, Lu SZ, Xu Y, Luo Z, Zhao Y, Lu H. 14-3-3gamma binds to MDMX that is phosphorylated by UV-activated Chk1, resulting in p53 activation. EMBO J. 2006 Mar 22; 25(6):1207-18. PMID: 16511572.
    View in: PubMed
  33. Boden G, She P, Mozzoli M, Cheung P, Gumireddy K, Reddy P, Xiang X, Luo Z, Ruderman N. Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappaB pathway in rat liver. Diabetes. 2005 Dec; 54(12):3458-65. PMID: 16306362.
    View in: PubMed
  34. Zhu J, Balan V, Bronisz A, Balan K, Sun H, Leicht DT, Luo Z, Qin J, Avruch J, Tzivion G. Identification of Raf-1 S471 as a novel phosphorylation site critical for Raf-1 and B-Raf kinase activities and for MEK binding. Mol Biol Cell. 2005 Oct; 16(10):4733-44. PMID: 16093354.
    View in: PubMed
  35. Luo Z, Saha AK, Xiang X, Ruderman NB. AMPK, the metabolic syndrome and cancer. Trends Pharmacol Sci. 2005 Feb; 26(2):69-76. PMID: 15681023.
    View in: PubMed
  36. Hayne C, Xiang X, Luo Z. MEK inhibition and phosphorylation of serine 4 on B23 are two coincident events in mitosis. Biochem Biophys Res Commun. 2004 Aug 27; 321(3):675-80. PMID: 15358159.
    View in: PubMed
  37. Xiang X, Saha AK, Wen R, Ruderman NB, Luo Z. AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms. Biochem Biophys Res Commun. 2004 Aug 13; 321(1):161-7. PMID: 15358229.
    View in: PubMed
  38. Kelly M, Keller C, Avilucea PR, Keller P, Luo Z, Xiang X, Giralt M, Hidalgo J, Saha AK, Pedersen BK, Ruderman NB. AMPK activity is diminished in tissues of IL-6 knockout mice: the effect of exercise. Biochem Biophys Res Commun. 2004 Jul 23; 320(2):449-54. PMID: 15219849.
    View in: PubMed
  39. Tomas E, Kelly M, Xiang X, Tsao TS, Keller C, Keller P, Luo Z, Lodish H, Saha AK, Unger R, Ruderman NB. Metabolic and hormonal interactions between muscle and adipose tissue. Proc Nutr Soc. 2004 May; 63(2):381-5. PMID: 15294059.
    View in: PubMed
  40. Cai D, Iyer A, Felekkis KN, Near RI, Luo Z, Chernoff J, Albanese C, Pestell RG, Lerner A. AND-34/BCAR3, a GDP exchange factor whose overexpression confers antiestrogen resistance, activates Rac, PAK1, and the cyclin D1 promoter. Cancer Res. 2003 Oct 15; 63(20):6802-8. PMID: 14583477.
    View in: PubMed
  41. Song Y, Zhao L, Tao W, Laties AM, Luo Z, Wen R. Photoreceptor protection by cardiotrophin-1 in transgenic rats with the rhodopsin mutation s334ter. Invest Ophthalmol Vis Sci. 2003 Sep; 44(9):4069-75. PMID: 12939330.
    View in: PubMed
  42. Huang YZ, Zang M, Xiong WC, Luo Z, Mei L. Erbin suppresses the MAP kinase pathway. J Biol Chem. 2003 Jan 10; 278(2):1108-14. PMID: 12379659.
    View in: PubMed
  43. Xiang X, Zang M, Waelde CA, Wen R, Luo Z. Phosphorylation of 338SSYY341 regulates specific interaction between Raf-1 and MEK1. J Biol Chem. 2002 Nov 22; 277(47):44996-5003. PMID: 12244094.
    View in: PubMed
  44. Xu CW, Luo Z. Inactivation of Ras function by allele-specific peptide aptamers. Oncogene. 2002 Aug 22; 21(37):5753-7. PMID: 12173045.
    View in: PubMed
  45. Luo ZG, Wang Q, Zhou JZ, Wang J, Luo Z, Liu M, He X, Wynshaw-Boris A, Xiong WC, Lu B, Mei L. Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1. Neuron. 2002 Aug 1; 35(3):489-505. PMID: 12165471.
    View in: PubMed
  46. Tomás E, Lin YS, Dagher Z, Saha A, Luo Z, Ido Y, Ruderman NB. Hyperglycemia and insulin resistance: possible mechanisms. Ann N Y Acad Sci. 2002 Jun; 967:43-51. PMID: 12079834.
    View in: PubMed
  47. Xiang X, Yuan M, Song Y, Ruderman N, Wen R, Luo Z. 14-3-3 facilitates insulin-stimulated intracellular trafficking of insulin receptor substrate 1. Mol Endocrinol. 2002 Mar; 16(3):552-62. PMID: 11875115.
    View in: PubMed
  48. Zang M, Hayne C, Luo Z. Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1. J Biol Chem. 2002 Feb 8; 277(6):4395-405. PMID: 11733498.
    View in: PubMed
  49. Lin Y, Itani SI, Kurowski TG, Dean DJ, Luo Z, Yaney GC, Ruderman NB. Inhibition of insulin signaling and glycogen synthesis by phorbol dibutyrate in rat skeletal muscle. Am J Physiol Endocrinol Metab. 2001 Jul; 281(1):E8-E15. PMID: 11404218.
    View in: PubMed
  50. Lenz G, Gonçalves D, Luo Z, Avruch J, Rodnight R, Neary JT. Extracellular ATP stimulates an inhibitory pathway towards growth factor-induced cRaf-1 and MEKK activation in astrocyte cultures. J Neurochem. 2001 May; 77(4):1001-9. PMID: 11359865.
    View in: PubMed
  51. Zang M, Waelde CA, Xiang X, Rana A, Wen R, Luo Z. Microtubule integrity regulates Pak leading to Ras-independent activation of Raf-1. insights into mechanisms of Raf-1 activation. J Biol Chem. 2001 Jul 6; 276(27):25157-65. PMID: 11274179.
    View in: PubMed
  52. Avruch J, Khokhlatchev A, Kyriakis JM, Luo Z, Tzivion G, Vavvas D, Zhang XF. Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade. Recent Prog Horm Res. 2001; 56:127-55. PMID: 11237210.
    View in: PubMed
  53. Hayne C, Tzivion G, Luo Z. Raf-1/MEK/MAPK pathway is necessary for the G2/M transition induced by nocodazole. J Biol Chem. 2000 Oct 13; 275(41):31876-82. PMID: 10884385.
    View in: PubMed
  54. Tzivion G, Luo ZJ, Avruch J. Calyculin A-induced vimentin phosphorylation sequesters 14-3-3 and displaces other 14-3-3 partners in vivo. J Biol Chem. 2000 Sep 22; 275(38):29772-8. PMID: 10887173.
    View in: PubMed
  55. Lenz G, Gottfried C, Luo Z, Avruch J, Rodnight R, Nie WJ, Kang Y, Neary JT. P(2Y) purinoceptor subtypes recruit different mek activators in astrocytes. Br J Pharmacol. 2000 Mar; 129(5):927-36. PMID: 10696092.
    View in: PubMed
  56. Peng M, Li Y, Luo Z, Liu C, Laties AM, Wen R. Alpha2-adrenergic agonists selectively activate extracellular signal-regulated kinases in Müller cells in vivo. Invest Ophthalmol Vis Sci. 1998 Aug; 39(9):1721-6. PMID: 9699562.
    View in: PubMed
  57. Tzivion G, Luo Z, Avruch J. A dimeric 14-3-3 protein is an essential cofactor for Raf kinase activity. Nature. 1998 Jul 2; 394(6688):88-92. PMID: 9665134.
    View in: PubMed
  58. Marti A, Luo Z, Cunningham C, Ohta Y, Hartwig J, Stossel TP, Kyriakis JM, Avruch J. Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells. J Biol Chem. 1997 Jan 31; 272(5):2620-8. PMID: 9006895.
    View in: PubMed
  59. Luo Z, Diaz B, Marshall MS, Avruch J. An intact Raf zinc finger is required for optimal binding to processed Ras and for ras-dependent Raf activation in situ. Mol Cell Biol. 1997 Jan; 17(1):46-53. PMID: 8972184.
    View in: PubMed
  60. Luo Z, Tzivion G, Belshaw PJ, Vavvas D, Marshall M, Avruch J. Oligomerization activates c-Raf-1 through a Ras-dependent mechanism. Nature. 1996 Sep 12; 383(6596):181-5. PMID: 8774885.
    View in: PubMed
  61. Si J, Luo Z, Mei L. Induction of acetylcholine receptor gene expression by ARIA requires activation of mitogen-activated protein kinase. J Biol Chem. 1996 Aug 16; 271(33):19752-9. PMID: 8702681.
    View in: PubMed
  62. Luo ZJ, Zhang XF, Rapp U, Avruch J. Identification of the 14.3.3 zeta domains important for self-association and Raf binding. J Biol Chem. 1995 Oct 6; 270(40):23681-7. PMID: 7559537.
    View in: PubMed
  63. Singh IS, Luo Z, Kozlowski MT, Erlichman J. Association of USF and c-Myc with a helix-loop-helix-consensus motif in the core promoter of the murine type II beta regulatory subunit gene of cyclic adenosine 3', 5'-monophosphate-dependent protein kinase. Mol Endocrinol. 1994 Sep; 8(9):1163-74. PMID: 7838149.
    View in: PubMed
  64. Keryer G, Luo Z, Cavadore JC, Erlichman J, Bornens M. Phosphorylation of the regulatory subunit of type II beta cAMP-dependent protein kinase by cyclin B/p34cdc2 kinase impairs its binding to microtubule-associated protein 2. Proc Natl Acad Sci U S A. 1993 Jun 15; 90(12):5418-22. PMID: 8516283.
    View in: PubMed
  65. Luo Z, Singh IS, Fujihira T, Erlichman J. Characterization of a minimal promoter element required for transcription of the mouse type II beta regulatory subunit (RII beta) of cAMP-dependent protein kinase. J Biol Chem. 1992 Dec 5; 267(34):24738-47. PMID: 1332964.
    View in: PubMed
  66. Singh IS, Luo ZJ, Eng A, Erlichman J. Molecular cloning and characterization of the promoter region of the mouse regulatory subunit RII beta of type II cAMP-dependent protein kinase. Biochem Biophys Res Commun. 1991 Jul 15; 178(1):221-6. PMID: 2069562.
    View in: PubMed
  67. Luo Z, Shafit-Zagardo B, Erlichman J. Identification of the MAP2- and P75-binding domain in the regulatory subunit (RII beta) of type II cAMP-dependent protein kinase. Cloning and expression of the cDNA for bovine brain RII beta. J Biol Chem. 1990 Dec 15; 265(35):21804-10. PMID: 2254332.
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  68. Luo ZJ, Du CS, Tokunaga K, Omoto K. Genetic polymorphism of properdin factor B (BF) in a Chinese population: existence of two rare variants. Jinrui Idengaku Zasshi. 1987 Mar; 32(1):33-8. PMID: 3649419.
    View in: PubMed
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