Bing Lim, MD, PhD

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 667-5256
Fax: (617) 667-3299


blim@caregroup.harvard.edu

Bing Lim, MD, PhD

Beth Israel Deaconess Medical Center

EDUCATIONAL TITLES

  • Associate Professor, Medicine, Harvard Medical School
  • Associate Physician, Hematology/Oncology, Beth Israel Deaconess Medical Center

DF/HCC PROGRAM AFFILIATION

Research Abstract

The laboratory has three areas of research focus with an overall interest in the functional genomics of stem cell biology. One research focus is elucidating the function and regulation of the Rho/Rac/CDC42 sub-family of small GTP-binding proteins. We have cloned two novel GDP-Dissociation Inhibitors for Rho-GTPases. Function of these molecules are being studied by biochemical and genetic approach.

A second focus is the function of a novel lysosomal membrane protein, LAPTm5. The gene is expressed in embryonic and hematopoietic cells and appears to be involved in a novel regulatory function in proteolysis. A third focus is to develop strategies for using embryonal stem cells in functional genomics. We are also developing gene trap vectors to identify genes that are critical for ES cell differentiation.

Publications

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  • Loh KM, Lim B, Ang LT. Ex uno plures: molecular designs for embryonic pluripotency. Physiol. Rev. 2014; 95:245-95. PubMed
  • Tan HK, Toh CX, Ma D, Yang B, Liu TM, Lu J, Wong CW, Tan TK, Li H, Syn C, Tan EL, Lim B, Lim YP, Cook SA, Loh YH. Human Finger-Prick Induced Pluripotent Stem Cells Facilitate the Development of Stem Cell Banking. Stem Cells Transl Med 2014. PubMed
  • Loh KM, Ang LT, Zhang J, Kumar V, Ang J, Auyeong JQ, Lee KL, Choo SH, Lim CY, Nichane M, Tan J, Noghabi MS, Azzola L, Ng ES, Durruthy-Durruthy J, Sebastiano V, Poellinger L, Elefanty AG, Stanley EG, Chen Q, Prabhakar S, Weissman IL, Lim B. Efficient endoderm induction from human pluripotent stem cells by logically directing signals controlling lineage bifurcations. Cell Stem Cell 2014; 14:237-52. PubMed
  • Loh KM, Lim B. Stem cells: Close encounters with full potential. Nature 2013; 502:41-2. PubMed
  • Bartlett A, Buhlmann JE, Stone J, Lim B, Barrington RA. Multiple checkpoint breach of B cell tolerance in Rasgrp1-deficient mice. J Immunol 2013; 191:3605-13. PubMed
  • Tam WL, Lu H, Buikhuisen J, Soh BS, Lim E, Reinhardt F, Wu ZJ, Krall JA, Bierie B, Guo W, Chen X, Liu XS, Brown M, Lim B, Weinberg RA. Protein kinase C 留 is a central signaling node and therapeutic target for breast cancer stem cells. Cancer Cell 2013; 24:347-64. PubMed
  • Zhang L, Prak L, Rayon-Estrada V, Thiru P, Flygare J, Lim B, Lodish HF. ZFP36L2 is required for self-renewal of early burst-forming unit erythroid progenitors. Nature 2013; 499:92-6. PubMed
  • Arya SK, Lim B, Rahman AR. Enrichment, detection and clinical significance of circulating tumor cells. Lab Chip 2013; 13:1995-2027. PubMed
  • Loh KM, Lim B. Epigenetics: Actors in the cell reprogramming drama. Nature 2012; 488:599-600. PubMed
  • Liu TM, Ng WM, Tan HS, Vinitha D, Yang Z, Fan JB, Zou Y, Hui JH, Lee EH, Lim B. Molecular Basis of Immortalization of Human Mesenchymal Stem Cells by Combination of p53 Knockdown and Human Telomerase Reverse Transcriptase Overexpression. Stem Cells Dev 2012. PubMed
  • Orlov Y, Xu H, Afonnikov D, Lim B, Heng JC, Yuan P, Chen M, Yan J, Clarke N, Orlova N, Huss M, Gunbin K, Podkolodnyy N, Ng HH. Computer and statistical analysis of transcription factor binding and chromatin modifications by ChIP-seq data in embryonic stem cell. J Integr Bioinform 2012; 9:211. PubMed
  • Loh KM, Lim B. A precarious balance: pluripotency factors as lineage specifiers. Cell Stem Cell 2011; 8:363-9. PubMed
  • Zhang L, Flygare J, Wong P, Lim B, Lodish HF. miR-191 regulates mouse erythroblast enucleation by down-regulating Riok3 and Mxi1. Genes Dev 2011; 25:119-24. PubMed
  • Wang H, Zeng X, Fan Z, Lim B. RhoH modulates pre-TCR and TCR signalling by regulating LCK. Cell Signal 2010; 23:249-58. PubMed
  • Jayapal SR, Lee KL, Ji P, Kaldis P, Lim B, Lodish HF. Down-regulation of Myc is essential for terminal erythroid maturation. J Biol Chem 2010; 285:40252-65. PubMed
  • Chia NY, Chan YS, Feng B, Lu X, Orlov YL, Moreau D, Kumar P, Yang L, Jiang J, Lau MS, Huss M, Soh BS, Kraus P, Li P, Lufkin T, Lim B, Clarke ND, Bard F, Ng HH. A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity. Nature 2010; 468:316-20. PubMed
  • Loh KM, Lim B. Recreating pluripotency? Cell Stem Cell 2010; 7:137-9. PubMed
  • Wang H, Zeng X, Fan Z, Lim B. RhoH plays distinct roles in T-cell migrations induced by different doses of SDF1alpha. Cell Signal 2010; 22:1022-32. PubMed
  • Han J, Yuan P, Yang H, Zhang J, Soh BS, Li P, Lim SL, Cao S, Tay J, Orlov YL, Lufkin T, Ng HH, Tam WL, Lim B. Tbx3 improves the germ-line competency of induced pluripotent stem cells. Nature 2010; 463:1096-100. PubMed
  • Heng JC, Feng B, Han J, Jiang J, Kraus P, Ng JH, Orlov YL, Huss M, Yang L, Lufkin T, Lim B, Ng HH. The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent cells. Cell Stem Cell 2010; 6:167-74. PubMed
  • Sheik Mohamed J, Gaughwin PM, Lim B, Robson P, Lipovich L. Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells. RNA 2010; 16:324-37. PubMed
  • Jiang S, Lee BC, Fu Y, Avraham S, Lim B, Avraham HK. Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation. PLoS ONE 2010; 5:e9707. PubMed
  • Yuan P, Han J, Guo G, Orlov YL, Huss M, Loh YH, Yaw LP, Robson P, Lim B, Ng HH. Eset partners with Oct4 to restrict extraembryonic trophoblast lineage potential in embryonic stem cells. Genes Dev 2009; 23:2507-20. PubMed
  • Le MT, Xie H, Zhou B, Chia PH, Rizk P, Um M, Udolph G, Yang H, Lim B, Lodish HF. MicroRNA-125b promotes neuronal differentiation in human cells by repressing multiple targets. Mol Cell Biol 2009; 29:5290-305. PubMed
  • Liu TM,Wu YN,Guo XM,James Hoi Po H,Lee EH,Lim B. Effects of Ectopic Nanog and Oct4 Overexpression on Mesenchymal Stem Cells. Stem Cells Dev 2009; 18:1013-22. PubMed
  • Zhang J, Liu X, Datta A, Govindarajan K, Tam WL, Han J, George J, Wong C, Ramnarayanan K, Phua TY, Leong WY, Chan YS, Palanisamy N, Liu ET, Karuturi KM, Lim B, Miller LD. RCP is a human breast cancer-promoting gene with Ras-activating function. J Clin Invest 2009; 119:2171-83. PubMed
  • Le MT,Teh C,Shyh-Chang N,Xie H,Zhou B,Korzh V,Lodish HF,Lim B. MicroRNA-125b is a novel negative regulator of p53. Genes Dev 2009; 23:862-76. PubMed
  • Feng B,Jiang J,Kraus P,Ng JH,Heng JC,Chan YS,Yaw LP,Zhang W,Loh YH,Han J,Vega VB,Cacheux-Rataboul V,Lim B,Lufkin T,Ng HH. Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nat Cell Biol 2009; 11:197-203. PubMed
  • Dykxhoorn DM, Wu Y, Xie H, Yu F, Lal A, Petrocca F, Martinvalet D, Song E, Lim B, Lieberman J. miR-200 enhances mouse breast cancer cell colonization to form distant metastases. PLoS ONE 2009; 4:e7181. PubMed
  • Lim CY,Tam WL,Zhang J,Ang HS,Jia H,Lipovich L,Ng HH,Wei CL,Sung WK,Robson P,Yang H,Lim B. Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages. Cell Stem Cell 2008; 3:543-54. PubMed
  • Tay Y,Zhang J,Thomson AM,Lim B,Rigoutsos I. MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 2008; 455:1124-8. PubMed
  • Xiao S,Jin H,Korn T,Liu SM,Oukka M,Lim B,Kuchroo VK. Retinoic acid increases Foxp3+ regulatory T cells and inhibits development of Th17 cells by enhancing TGF-beta-driven Smad3 signaling and inhibiting IL-6 and IL-23 receptor expression. J Immunol 2008; 181:2277-84. PubMed
  • Tam WL,Lim CY,Han J,Zhang J,Ang YS,Ng HH,Yang H,Lim B. T-cell factor 3 regulates embryonic stem cell pluripotency and self-renewal by the transcriptional control of multiple lineage pathways. Stem Cells 2008; 26:2019-31. PubMed
  • Song CW, Chae JJ, Choi EK, Hwang TS, Kim C, Lim BU, Park HJ. Anti-cancer effect of bio-reductive drug beta-lapachon is enhanced by activating NQO1 with heat shock. Int J Hyperthermia 2008; 24:161-9. PubMed
  • Tay YM, Tam WL, Ang YS, Gaughwin PM, Yang H, Wang W, Liu R, George J, Ng HH, Perera RJ, Lufkin T, Rigoutsos I, Thomson AM, Lim B. MicroRNA-134 modulates the differentiation of mouse embryonic stem cells, where it causes post-transcriptional attenuation of Nanog and LRH1. Stem Cells 2007; 26:17-29. PubMed
  • Tarasov KV,Tarasova YS,Tam WL,Riordon DR,Elliott ST,Kania G,Li J,Yamanaka S,Crider DG,Testa G,Li RA,Lim B,Stewart CL,Liu Y,Van Eyk JE,Wersto RP,Wobus AM,Boheler KR. B-MYB is essential for normal cell cycle progression and chromosomal stability of embryonic stem cells. PLoS ONE 2008; 3:e2478. PubMed
  • Choi EK, Ji IM, Lee SR, Kook YH, Griffin RJ, Lim BU, Kim JS, Lee DS, Song CW, Park HJ. Radiosensitization of tumor cells by modulation of ATM kinase. Int J Radiat Biol 2006; 82:277-83. PubMed
  • Li X, Bu X, Lu B, Avraham H, Flavell RA, Lim B. The hematopoiesis-specific GTP-binding protein RhoH is GTPase deficient and modulates activities of other Rho GTPases by an inhibitory function. Mol Cell Biol 2002; 22:1158-71. PubMed
  • Gu H, Saito K, Klaman LD, Shen J, Fleming T, Wang Y, Pratt JC, Lin G, Lim B, Kinet JP, Neel BG. Essential role for Gab2 in the allergic response. Nature 2001; 412:186-90. PubMed
  • Cuervo AM, Hu W, Lim B, Dice JF. IkappaB is a substrate for a selective pathway of lysosomal proteolysis. Mol Biol Cell 1998; 9:1995-2010. PubMed
  • Guillemot JC, Kruskal BA, Adra CN, Zhu S, Ko JL, Burch P, Nocka K, Seetoo K, Simons E, Lim B. Targeted disruption of guanosine diphosphate-dissociation inhibitor for Rho-related proteins, GDID4: normal hematopoietic differentiation but subtle defect in superoxide production by macrophages derived from in vitro embryonal stem cell differentiation. Blood 1996; 88:2722-31. PubMed
  • Sansilvestri P, Cardoso AA, Batard P, Panterne B, Hatzfeld A, Lim B, L. Early CD34high cells can be separated into KIThigh cells in which transforming growth factor-beta (TGF-beta) downmodulates c-kit and KITlow cells in which anti-TGF-beta upmodulates c-kit. Blood 1995; 86:1729-35. PubMed
  • Adra CN, Kobayashi H, Rowley JD, Lim B. Assignment of the human GDID4 gene, a GDP/GTP-exchange regulator, to chromosome 12p12.3. Genomics 1994; 24:188-90. PubMed
  • Adra CN, Lelias JM, Kobayashi H, Kaghad M, Morrison P, Rowley JD, Lim B. Cloning of the cDNA for a hematopoietic cell-specific protein related to CD20 and the beta subunit of the high-affinity IgE receptor: evidence for a family of proteins with four membrane-spanning regions. Proc Natl Acad Sci U S A 1994; 91:10178-52. PubMed
  • Voso MT, Burn TC, Wulf G, Lim B, Leone G, Tenen DG. Inhibition of hematopoiesis by competitive binding of transcription factor PU.1. Proc Natl Acad Sci U S A 1994; 91:7932-6. PubMed
  • Wulf GM, Adra CN, Lim B. Inhibition of hematopoietic development from embryonic stem cells by antisense vav RNA. EMBO J 1993; 12:5065-74. PubMed
  • Adra CN, Ko J, Leonard D, Wirth LJ, Cerione RA, Lim B. Identification of a novel protein with GDP dissociation inhibitor activity for the ras-like proteins CDC42Hs and rac I. Genes Chromosomes Cancer 1993; 8:253-61. PubMed
  • Steinberg HN, Anderson J, Lim B, Chatis PA. Cytomegalovirus infection of the BS-1 human stroma cell line: effect on murine hemopoiesis. Virology 1993; 196:427-32. PubMed
  • Lelias JM, Adra CN, Wulf GM, Guillemot JC, Khagad M, Caput D, Lim B. cDNA cloning of a human mRNA preferentially expressed in hematopoietic cells and with homology to a GDP-dissociation inhibitor for the rho GTP-binding proteins. Proc Natl Acad Sci U S A 1993; 90:1479-83. PubMed
  • Scadden DT, Zeira M, Woon A, Wang Z, Schieve L, Ikeuchi K, Lim B, Groopman JE. Human immunodeficiency virus infection of human bone marrow stromal fibroblasts. Blood 1990; 76:317-22. PubMed
  • Lim B, Apperley JF, Orkin SH, Williams DA. Long-term expression of human adenosine deaminase in mice transplanted with retrovirus-infected hematopoietic stem cells. Proc Natl Acad Sci U S A 1989; 86:8892-6. PubMed
  • Williams DA, Lim B, Spooncer E, Longtine J, Dexter TM. Restriction of expression of an integrated recombinant retrovirus in primary but not immortalized murine hematopoietic stem cells. Blood 1988; 71:1738-43. PubMed
  • Tweeddale ME, Lim B, Jamal N, Robinson J, Zalcberg J, Lockwood G, Minden MD, Messner HA. The presence of clonogenic cells in high-grade malignant lymphoma: a prognostic factor. Blood 1987; 69:1307-14. PubMed
  • Williams DA, Lim B, Orkin SH. Transfer and expression of human ADA in murine hematopoietic stem cells. Prog Clin Biol Res 1986; 251:567-80. PubMed
  • Lim B, Izaguirre CA, Aye MT, Huebsch L, Drouin J, Richardson C, Minden MD, Messner HA. Characterization of reticulofibroblastoid colonies (CFU-RF) derived from bone marrow and long-term marrow culture monolayers. J Cell Physiol 1986; 127:45-54. PubMed
  • Denburg JA, Telizyn S, Messner H, Lim B, Jamal N, Ackerman SJ, Gleich GJ, Bienenstock J. Heterogeneity of human peripheral blood eosinophil-type colonies: evidence for a common basophil-eosinophil progenitor. Blood 1985; 66:312-8. PubMed
  • Denburg JA, Messner H, Lim B, Jamal N, Telizyn S, Bienenstock J. Clonal origin of human basophil/mast cells from circulating multipotent hemopoietic progenitors. Exp Hematol 1985; 13:185-8. PubMed
  • Lim B, Jamal N, Messner HA. Flexible association of hemopoietic differentiation programs in multilineage colonies. J Cell Physiol 1984; 121:291-7. PubMed
  • Lim B, Jamal N, Tritchler D, Messner HA. G6PD isoenzyme analysis of myeloid and lymphoid cells in human multilineage colonies. Blood 1984; 63:1481-7. PubMed
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