Photo of Hongbo R. Luo,  PhD

Hongbo R. Luo, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2303
Fax: (617) 730-0885


Hongbo.Luo@childrens.harvard.edu

Hongbo R. Luo, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Associate Professor, Pathology, Harvard Medical School
  • Associate professor, Lab Medicine, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our research focuses on signaling pathways triggered by inositol phospholipid PtdIns(3,4,5)P3, which has been implicated in various cellular processes such as proliferation, growth, apoptosis, polarity, chemotaxis and cytoskeletal rearrangement. PtdIns(3,4,5)P3 exerts its function by mediating protein translocation via binding to their pleckstrin homolog (PH)-domains. Membrane translocation of PH-domains was previously thought to be dependent solely upon concentrations of PtdIns(3,4,5)P3 in the membrane which is regulated by PI3K and PTEN. Recently, we discovered that two intracellular inositol phosphates InsP7 and Ins(1,3,4,5)P4 compete with PtdIns(3,4,5)P3 for binding to the PH domains, and thereby attenuate their membrane translocation. This result provides another level of regulation for PH domain translocation, namely relative levels of InsP7 and PtdIns(3,4,5)P3. Our lab will continue to elucidate the molecular mechanism and the physiological consequence of the inositol phosphate-mediated suppression of PtdIns(3,4,5)P3 signaling in a variety of cellular processes. #p Our lab is also interested in the role of neutrophils and innate immunity in hematopoiesis and leukemogenesis. Neutrophils in the bone marrow and circulation release various factors that can modulate hematopoiesis and myelopoiesis. We are currently exploring the role of ROS and proteases in infection-induced myelopoiesis. We are also interested in the molecular and cellular mechanisms that govern the release (mobilization) of neutrophils from the bone marrow during the course of inflammation. Similar mechanisms may also be involved in mobilization of leukemia cells.

Publications

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  • Qi Q, Li DY, Luo HR, Guan KL, Ye K. Netrin-1 exerts oncogenic activities through enhancing Yes-associated protein stability. Proc Natl Acad Sci U S A 2015; 112:7255-60. PubMed
  • Kaunisto A, Henry WS, Montaser-Kouhsari L, Jaminet SC, Oh EY, Zhao L, Luo HR, Beck AH, Toker A. NFAT1 promotes intratumoral neutrophil infiltration by regulating IL8 expression in breast cancer. Mol Oncol 2015. PubMed
  • Luo HR, Mondal S. Molecular control of PtdIns(3,4,5)P3 signaling in neutrophils. EMBO Rep. 2015; 16:149-63. PubMed
  • Kwak HJ, Liu P, Bajrami B, Xu Y, Park SY, Nombela-Arrieta C, Mondal S, Sun Y, Zhu H, Chai L, Silberstein LE, Cheng T, Luo HR. Myeloid cell-derived reactive oxygen species externally regulate the proliferation of myeloid progenitors in emergency granulopoiesis. Immunity 2015; 42:159-71. PubMed
  • Loison F, Zhu H, Karatepe K, Kasorn A, Liu P, Ye K, Zhou J, Cao S, Gong H, Jenne DE, Remold-O'Donnell E, Xu Y, Luo HR. Proteinase 3-dependent caspase-3 cleavage modulates neutrophil death and inflammation. J Clin Invest 2014; 124:4445-58. PubMed
  • Jo H, Loison F, Luo HR. Microtubule dynamics regulates Akt signaling via dynactin p150. Cell Signal 2014. PubMed
  • Hongbo R. Luo. A dual regulator of neutrophil recruitment Blood 2014; 123:1983.
  • Liang OD, Lu J, Nombela-Arrieta C, Zhong J, Zhao L, Pivarnik G, Mondal S, Chai L, Silberstein LE, Luo HR. Deficiency of lipid phosphatase SHIP enables long-term reconstitution of hematopoietic inductive bone marrow microenvironment. Dev Cell 2013; 25:333-49. PubMed
  • Jo H, Mondal S, Tan D, Nagata E, Takizawa S, Sharma AK, Hou Q, Shanmugasundaram K, Prasad A, Tung JK, Tejeda AO, Man H, Rigby AC, Luo HR. Small molecule-induced cytosolic activation of protein kinase Akt rescues ischemia-elicited neuronal death. Proc Natl Acad Sci U S A 2012; 109:10581-6. PubMed
  • Sakai, J., Li, J., Subramanian, K.K., Mondal, S., Bajrami, B., Hattori, H., Jia, Y., Dickinson, B.C., Zhong, J., Ye, K., Chang, C.J., Ho, Y.S., Zhou, J., and Luo, H.R. Reactive oxygen species (ROS)-induced actin glutathionylation and its modulation by glutaredoxin 1 are key physiological regulatory mechanisms controlling actin dynamics in neutrophils Immunity 2012; 37:1037-1049.
  • Jo H, Lo PK, Li Y, Loison F, Green S, Wang J, Silberstein LE, Ye K, Chen H, Luo HR. Deactivation of Akt by a small molecule inhibitor targeting pleckstrin homology domain and facilitating Akt ubiquitination. Proc Natl Acad Sci U S A 2011. PubMed
  • Prasad, A., Y. Jia, A. Chakraborty, Y. Li, S.K. Jain, J. Zhong, S.G. Roy, F. Loison, S. Mondal, J. Sakai, C. Blanchard, S.H. Snyder, and H.R. Luo. Inositol hexakisphosphate kinase 1 regulates neutrophil function in innate immunity by inhibiting phosphatidylinositol-(3,4,5)-trisphosphate signaling Nat Immunol 2011; 12:752.
  • Carbo C, Duerschmied D, Goerge T, Hattori H, Sakai J, Cifuni SM, White GC, Chrzanowska-Wodnicka M, Luo HR, Wagner DD. Integrin-independent role of CalDAG-GEFI in neutrophil chemotaxis. J Leukoc Biol 2010; 88:313-9. PubMed
  • Yu H, Li Y, Gao C, Fabien L, Jia Y, Lu J, Silberstein LE, Pinkus GS, Ye K, Chai L, Luo HR. Relevant mouse model for human monocytic leukemia through Cre/lox-controlled myeloid-specific deletion of PTEN. Leukemia 2010; 24:1077-80. PubMed
  • Simarro M, Giannattasio G, De la Fuente MA, Benarafa C, Subramanian KK, Ishizawar R, Balestrieri B, Andersson EM, Luo HR, Orduña A, Boyce J, Anderson P. Fas-activated serine/threonine phosphoprotein promotes immune-mediated pulmonary inflammation. J Immunol 2010; 184:5325-32. PubMed
  • Hattori H, Subramanian KK, Sakai J, Luo HR. Reactive oxygen species as signaling molecules in neutrophil chemotaxis. Commun Integr Biol 2010; 3:278-81. PubMed
  • Hattori H, Subramanian KK, Sakai J, Jia Y, Li Y, Porter TF, Loison F, Sarraj B, Kasorn A, Jo H, Blanchard C, Zirkle D, McDonald D, Pai SY, Serhan CN, Luo HR. Small-molecule screen identifies reactive oxygen species as key regulators of neutrophil chemotaxis. Proc Natl Acad Sci U S A 2010; 107:3546-51. PubMed
  • Xu Y, Loison F, Luo HR. Neutrophil spontaneous death is mediated by down-regulation of autocrine signaling through GPCR, PI3Kgamma, ROS, and actin. Proc Natl Acad Sci U S A 2010; 107:2950-5. PubMed
  • Jo H, Loison F, Hattori H, Silberstein LE, Yu H, Luo HR. Natural product Celastrol destabilizes tubulin heterodimer and facilitates mitotic cell death triggered by microtubule-targeting anti-cancer drugs. PLoS ONE 2010; 5:e10318. PubMed
  • Kasorn A, Alcaide P, Jia Y, Subramanian KK, Sarraj B, Li Y, Loison F, Hattori H, Silberstein LE, Luscinskas WF, Luo HR. Focal adhesion kinase regulates pathogen-killing capability and life span of neutrophils via mediating both adhesion-dependent and -independent cellular signals. J Immunol 2009; 183:1032-43. PubMed
  • Sarraj B,Massberg S,Li Y,Kasorn A,Subramanian K,Loison F,Silberstein LE,von Andrian U,Luo HR. Myeloid-specific deletion of tumor suppressor PTEN augments neutrophil transendothelial migration during inflammation. J Immunol 2009; 182:7190-200. PubMed
  • Li Y,Jia Y,Pichavant M,Loison F,Sarraj B,Kasorn A,You J,Robson BE,Umetsu DT,Mizgerd JP,Ye K,Luo HR. Targeted deletion of tumor suppressor PTEN augments neutrophil function and enhances host defense in neutropenia-associated pneumonia. Blood 2009; 113:4930-41. PubMed
  • Jia Y,Schurmans S,Luo HR. Regulation of innate immunity by inositol 1,3,4,5-tetrakisphosphate. Cell Cycle 2008; 7:2803-8. PubMed
  • Jo H, Jia Y, Subramanian KK, Hattori H, Luo HR. Cancer Cell-Derived Clusterin Modulates the PI3K-Akt Pathway through Attenuation of IGF-1 during Serum Deprivation. Mol Cell Biol 2008; 28:4285-99. PubMed
  • Luo HR, Loison F. Constitutive neutrophil apoptosis: mechanisms and regulation. Am J Hematol 2007; 83:288-95. PubMed
  • Liu Z, Jang SW, Liu X, Cheng D, Peng J, Yepes M, Li XJ, Matthews S, Watts C, Asano M, Hara-Nishimura I, Luo HR, Ye K. Neuroprotective actions of PIKE-L by inhibition of SET proteolytic degradation by asparagine endopeptidase. Mol Cell 2008; 29:665-78. PubMed
  • Jia Y, Loison F, Hattori H, Li Y, Erneux C, Park SY, Gao C, Chai L, Silberstein LE, Schurmans S, Luo HR. Inositol trisphosphate 3-kinase B (InsP3KB) as a physiological modulator of myelopoiesis. Proc Natl Acad Sci U S A 2008; 105:4739-44. PubMed
  • Le Y, Zhu BM, Harley B, Park SY, Kobayashi T, Manis JP, Luo HR, Yoshimura A, Hennighausen L, Silberstein LE. SOCS3 protein developmentally regulates the chemokine receptor CXCR4-FAK signaling pathway during B lymphopoiesis. Immunity 2007; 27:811-23. PubMed
  • Jia Y, Subramanian KK, Erneux C, Pouillon V, Hattori H, Jo H, You J, Zhu D, Schurmans S, Luo HR. Inositol 1,3,4,5-tetrakisphosphate negatively regulates phosphatidylinositol-3,4,5- trisphosphate signaling in neutrophils. Immunity 2007; 27:453-67. PubMed
  • Marechal Y, Pesesse X, Jia Y, Pouillon V, Perez-Morga D, Daniel J, Izui S, Cullen PJ, Leo O, Luo HR, Erneux C, Schurmans S. Inositol 1,3,4,5-tetrakisphosphate controls proapoptotic Bim gene expression and survival in B cells. Proc Natl Acad Sci U S A 2007; 104:13978-83. PubMed
  • Hattori H, Zhang X, Jia Y, Subramanian KK, Jo H, Loison F, Newburger PE, Luo HR. RNAi screen identifies UBE2D3 as a mediator of all-trans retinoic acid-induced cell growth arrest in human acute promyelocytic NB4 cells. Blood 2007; 110:640-50. PubMed
  • Luo HR, Hattori H, Hossain MA, Hester L, Huang Y, Lee-Kwon W, Donowitz M, Nagata E, Snyder SH. Akt as a mediator of cell death. Proc Natl Acad Sci U S A 2003; 100:11712-7. PubMed
  • Luo HR, Huang YE, Chen JC, Saiardi A, Iijima M, Ye K, Huang Y, Nagata E, Devreotes P, Snyder SH. Inositol pyrophosphates mediate chemotaxis in Dictyostelium via pleckstrin homology domain-PtdIns(3,4,5)P3 interactions. Cell 2003; 114:559-72. PubMed
  • Luo HR, Saiardi A, Yu H, Nagata E, Ye K, Snyder SH. Inositol pyrophosphates are required for DNA hyperrecombination in protein kinase c1 mutant yeast. Biochemistry 2002; 41:2509-15. PubMed
  • Luo HR, Saiardi A, Nagata E, Ye K, Yu H, Jung TS, Luo X, Jain S, Sawa A, Snyder SH. GRAB: a physiologic guanine nucleotide exchange factor for Rab3A, which interacts with inositol hexakisphosphate kinase. Neuron 2001; 31:439-51. PubMed
  • Fabien Loison1,2, Haiyan Zhu3, Kutay Karatepe1, Anongnard Kasorn1.4, Peng Liu3, Keqiang Ye5, Dieter E. Jenne6, Eileen Remold-O’Donnell7, Yuanfu Xu3, Hongbo R. Luo. Regulation of neutrophil death and inflammation by Proteinase 3 J Clin Invest 2014.
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