Bing Lim, M.D. Ph.D.
Senior Group Leader
limb1@gis.a-star.edu.sg
RESEARCH FOCUS
 

Bing Lim's Laboratory
Genome Institute of Singapore, Stem Cell & Developmental Biology Group;
Harvard Medical School and Beth Israel Deaconess Medical Center, Division of Hematology/Oncology

Our laboratory has related research interests concerning embryonic stem cells, lineage reprogramming, microRNAs, and hematopoiesis. We exploit au courant technology platforms inherent to the Genome Institute of Singapore to complement our research efforts. Our principal investigator, Dr. Bing Lim, has dual appointments as both a Senior Group Leader at the Genome Institute of Singapore as well as a Associate Professor at Harvard Medical School.

I. Embryonic Stem Cells and Pluripotentiality
Pluripotent cells, such as embryonic stem (ES) cells, are the foundation of mammalian development - they may generate any of the hundreds of diverse cell types within the mammalian body. ES cells have since been exploited as a wellspring that may continually generate any bodily cell type (e.g. a neuron or a cardiomyocyte) that we might require for clinical, translational, or research purposes.

We are interested in two issues pertaining to the translational exploitation of ES cells: (1) What underlies the faculty of ES cells to differentiate into all fetal cell types? and (2) How do we direct the differentiation of ES cells into specific differentiated cell types of therapeutic relevance?

Embryonic, hematopoietic, and neural stem cells are transcriptionally dissimilar
Do ES cells rely on mechanisms similar to those exploited by multipotential neural stem cells (NSCs) and hematopoietic stem cells (HSCs) to differentiate into many different cell types? We resolved this long-standing question by demonstrating that ES cells, HSCs, and NSCs are transcriptionally divergent, thus demonstrating that separate stem cell populations likely dependent on different transcriptional contrivances to maintain their multilineage differentiation potential (Fortunel et al., 2003; Science).

Identifying Sall4 as a novel, bona fide pluripotency transcription factor
Next, we focused specifically on what maintains the multilineage differentiation potential of ES cells. We identified an transcription factor, Sall4, that is required for ES cell pluripotentiality (Zhang et al., 2006; Nature Cell Biology). We found that Sall4 maintains ES cells in an undifferentiated, uncommitted state by prohibiting trophectodermal differentiation. Moreover, we also found that Sall4 probably enables ES cells to differentiate into endodermal lineages. In subsequent studies, we found that Sall4 is expressed in both pluripotential ES cells as well as extraembryonic endoderm (XEN) cells and that unexpectedly, it is important for both pluripotential as well as extraembryonic cells (Lim et al., 2008; Cell Stem Cell). We confirmed that Sall4 has divergent functions in ES cells versus XEN cells by mapping its genome-wide binding sites in both cell types using chromatin immunoprecipitation coupled to microarrays (chIP-chip).

A basis for the unlimited multilineage differentiation potential of ES cells
Studies such as our own have identified transcription factors (e.g., Sall4) whose expression is required to maintain pluripotency; when bereft of these so-called "pluripotency factors", ES cells differentiate to specific lineages. These findings have led to the prevailing paradigm that pluripotency factors practice lineage-specific blockades on ES cell differentiation, and expression of a panoply of diverse pluripotency factors precludes ES cell differentiation to any downstream lineage, hence enabling undifferentiated stem cell self-renewal. Nevertheless, such a theoretical model does not provide an explanation for the most quintessenial property of an ES cell - its remarkable ability to liberally differentiate into any cell type within the mammalian body! To this end, we have recently averred that many classical pluripotency transcription factors expressed by ES cells (e.g., Oct4, Sox2, Nanog et al.) indeed serve as lineage specification factors that provide ES cells with the ability to differentiate to specific fetal lineages (Loh and Lim, 2011; Cell Stem Cell). Expression of these lineage specifiers within ES cells grants them with a representation of all the transcription factors necessary to prosecute differentiation into the major fetal lineages (definitive endoderm, mesoderm, and definitive ectoderm). Our proposal is substantiated by emergent studies that pluripotency factors genuinely appear to masquerade as bona fide lineage specifiers; for example, Nanog specifies the differentiation of human ES cells to definitive endoderm while precluding specification to either mesoderm or neuroectoderm. Moreover, we predict that pluripotency is highly unstable due to continual conflict between pluripotency factors that are seeking to direct ES cell differentiation to specific lineages.

MicroRNAs specifying ES cell lineage commitment
Having defined components of the transcriptional regime that maintains the multilineage differentiation potential of ES cells, next we attempted to try to identify what mechanisms underlie ES cell differentiation and lineage specification. We identified three novel microRNAs that target the Oct4, Sox2, and Nanog coding sequences and are upregulated upon ES cell differentiation (Tay et al., 2008; Nature). Thus, it appears that ES cell lineage specification relies on the upregulation of microRNAs to suppress ES cell transcription factors that would otherwise inhibit differentiation. We also found another microRNA, miR-134, that directly specifies neuroectodermal commitment of ES cells via inhibition of Nanog and Nr5a2 protein translation (Tay et al., 2008; Stem Cells).

Tcf3 is required to prosecute ES cell differentiation
Furthermore, we also found an unexpected role for the transcription factor Tcf3 (the terminal effector of Wnt/β-catenin signaling) in conferring ES cells with the ability to differentiate, as knockdown of Tcf3 prevents ES cells from differentiating (Tam et al., 2008; Stem Cells). Such results were unanticipated, given previous high profile reports that Wnt/β-catenin signaling directs the undifferentiated self-renewal of ES cells. We demonstrated that Tcf3 likely orchestrates differentiation by downregulating Oct4 and Nanog while concomitantly upregulating a plethora of genes associated with lineage commitment.

Enabling undifferentiated self-renewal of human ES cells
Moving from mouse ES cells to therapeutically relevant human ES cells, we used microarray analyses to identify growth factor receptors expressed on the surface of human ES cells that might be important for regulating their self-renewal (Soh et al., 2008; Stem Cells). From these analyses, we identified that the pleiotrophin receptor is expressed on human ES cells that it is necessary for their self-renewal. From a practical perspective, addition of exogenous pleiotrophin enhances human ES cell propagation, making it useful for long-term human ES cell culture.

II. Lineage Reprogramming
Parsimoniously speaking, what makes one cell type different from another is lineage-specific transcription factor regimes that impart unique lineages with their unique gene expression programs. Such a paradigm would suggest that a cell could be directly reprogrammed to an alternative lineage by simply substituting its current cadre of transcription factors and epigenetic regulators with those that are expressed by another cell type. Indeed, this appears to be the case, as fibroblasts may be directly reprogrammed into induced pluripotent stem (iPS) cells, cardiomyocytes, neurons, or myocytes by simple overexpression of transcription factors that are expressed in these target cell types. Given our experience with pluripotential cells, an ongoing research focus in our lab is to reprogram differentiated cells into pluripotential iPS cells.

Efficient generation of "high quality" mouse iPS cells with Tbx3
Despite the recent excitement over iPS cells, a word of caution comes from the fact that nearly the majority of present (mouse) iPS cell lines are incapable of tetraploid complementation and thus are not bona fide pluripotential cells (Loh and Lim, 2010; Cell Stem Cell). With such thinking in mind, we set out to try to devise a method by which we could homogenously generate “high quality” iPS cells that are authentically pluripotent and are capable of tetraploid and diploid complementation. We found that overexpression of transcription factor Tbx3 reproducibly enables the creation of high quality mouse iPS cells with an enhanced capacity for diploid complementation, germline transmission, as well as tetraploid complementation (Han et al., 2010; Nature). This was the first such demonstration that the “quality” of iPS cells could be deterministically enhanced by defined factors.

III. MicroRNAs
Our present understanding of cell fate and physiology, especially in regards to pluripotential stem cells, is heavily focused on transcription factors. In our laboratory, we have sought to explore further the role of microRNAs in specific cell types of interest. As aforementioned, we have defined novel roles for various microRNAs in ES cell differentiation (Tay et al., 2008; Nature and Tay et al., 2008; Stem Cells). We also developed a novel algorithm to find the targets of microRNAs, and through this, we found that many microRNAs may have thousands of target transcripts, far more than previously believed (Miranda et al., 2006; Cell).

We also identified the first microRNA known to regulate the tumor suppressor p53—miR-125b (Le et al., 2009; Genes & Development). miR-125b downregulation is essential for activation of p53-orchestrated stress responses, and we also found an unanticipated role for it in regulating neuronal differentiation, as it is specifically expressed in the brain (Le et al., 2009; Molecular and Cellular Biology).

IV. Hematopoiesis
Our principal investigator—Dr. Bing Lim—did his graduate training with Earnest McCulloch, co-discoverer of hematopoietic stem cells. Thus, we have a consequential interest in hematopoietic stem cells and various other aspects of the hematopoietic system. Through a screen for genes preferentially expressed in hematopoietic cells, we identified and cloned D4 GDI (GDID4/RhoGDIβ), a member of the family of Rho GTPase guanosine disassociation inhibitors (Lelias et al., 1993; Proc Natl Acad Sci). Gdid4 deletion does not impair hematopoietic differentiation, but rather, Gdid4—/— macrophages are impaired in their superoxide production (Guillemot et al., 1996; Blood). Later, we discovered a closely related homolog to GDID4, which we named RhoGDIγ (Adra et al., 1997; Proc Natl Acad Sci). During our investigations of Gdid4 function, we noticed that Gdid4—/— mice often developed an autoimmune disease similar to the human disease systemic lupus erythematosus (Layer et al., 2003; Immunity). We were surprised to find that this autoimmune disorder was not the consequence of Gdid4 deficiency, but rather that these Gdid4—/— mice developed autoimmunity due to a spontaneous and unrelated mutation in the Ras guanine exchange factor Rasgrp1. This Rasgrp1 mutation was found to block Ras signaling, and led to the activation of B cells and autoantibody production, thus providing an excellent murine model for the lupus disorder.

We have also recently found that downregulation of c-Myc is required for the terminal differentiation of erythroblasts during erythropoiesis (Jayapal et al., 2010; J. Biol Chem). c-Myc inhibits nuclear condensation and enucleation of erythrocytes, and thus its downregulation is required for proper terminal differentiation.

V. Collaborations
We take a collaborative approach in all our research enterprises, and many of the above research achievements would have been impossible if not for the collaboration and support tendered by various investigators at Singapore, the United States, and elsewhere. In addition, we have been pleased to help many other research groups in their own research efforts.

Our list of recent collaborators includes but is certainly not limited to—Dr. Harvey Lodish (MIT/Whitehead: Le et al., 2009; Genes & Development; Le et al., 2009; Molecular Cellular Biology), Dr. Ludovic Vallier (Cambridge: Soh et al., 2008; Stem Cells), Dr. Henry Yang (A*STAR: Lim et al., 2008; Cell Stem Cell; Han et al., 2010; Nature), Dr. Huck-Hui Ng (A*STAR: Chia et al., 2010; Nature; Heng et al., 2010; Cell Stem Cell; Feng et al., 2009; Nature Cell Biology), and Dr. Isidore Rigoutsos (IBM: Tay et al., 2008; Nature; Tay et al., 2008; Stem Cells).

 

EDUCATION

1974 M.D., University of Western Ontario, Ontario, Canada

1986 Ph.D., University of Western Ontario, Ontario, Canada



Postdoctoral Training

Internship and Residencies:

1974-1975 Resident in Medicine, McMaster University, Hamilton, Canada

1975 Resident in General Surgery, McMaster University, Hamilton, Canada

1976-1977 Medical Officer, Queen Elizabeth Hospital, Sabah, Malaysia

1977-1979 Resident in Medicine, University of Western Ontario, Ontario, Canada

1979-1981 Fellow in Hematology/Oncology, Princess Margaret Hospital, University of Toronto, Canada



Clinical and Research Fellowships:

1981-1985 Ph.D. Program, Princess Margaret Hospital, University of Toronto, Institute of Medical Science

1985-1988 Post-doctoral Research Fellow, Childrens Hospital, Harvard Medical School, Boston, MA



Licensure and Certification:

1980 American Board of Internal Medicine

1980 F.R.C.P. (C) Fellow of Royal College of Physicians

 

PROFESSIONAL APPOINTMENTS

  Academic Appointments

1988-1993 Instructor in Medicine, Harvard Medical School.

1993-1997 Assistant Professor of Medicine, Harvard Medical School

1998- Associate Professor of Medicine, Harvard Medical School

2002- Senior Group Leader, Genome Institute of Singapore



Hospital Appointments

1998- Associate Physician, Beth Israel Hospital, Harvard Medical School

 

HONORS AND AWARDS

1993-1998 Scholar of the Leukemia Society of America

1987-1988 Howard Hughes Postdoctoral Fellowship

1985-1987 M.R.C. Fellowship (Postdoctoral)

1981-1985 M.R.C. Fellowship (Ph.D.)

1974 Charles E. Frost Medal and Award (for clinical therapeutics and medicine)

1973 Alpha Omega Alpha

1969 William Wyatt Scholarship (for best undergraduate entering honors course)

1968-1974 Dean's Honors List (Every year)

1968-1974 Colombo Plan Scholarship (Medicine)

 

COMMITTEE AND ADVISORY BOARD

National and Regional

1995-2000 HEM-2 Study Section; Member of Ad Hoc Grant review Comitee for National Institute of Health, U.S.A.

2003- Blood Development Study Section Ad Hoc Grant review, NIH, U.S.A.

1994-1996 Drug, Hematology and Pharmacology Study Section; Member of Grant Review Committee for American Cancer Society.

1997- Leukemia and Blood Development Study Section; Member of Grant Reviw Committee, American Cancer Society

1998-2004 Editorial Board. BLOOD Journal

2004- Grant Review Committee, Basic Science Section, BMRC, Singapore



International

1994- Ad Hoc External Reviewer for Canadian Red Corss Reviewer Grants

1996- Ad Hoc External Reviewer, International Human Frontier Science Program

1998- External Reviewer, Italian University Grants Warrant Committee

2004 Steering Committee Member, International Regulome Consortium

 

COMPLETE PUBLICATION LIST

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 Jan 15 ; 25(2) : 119-24 Epub 2010 Dec 31
Abstract
 
Loh KM and Lim B* "A precarious balance: pluripotency factors as lineage specifiers." Cell Stem Cell 2011 Apr 8 ; 8(4) : 363-9
Abstract
 
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 Feb 25 ; 463(7284) : 1096-100 Epub 2010 Feb 7
Abstract
 
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 Feb 5 ; 6(2) : 167-74 Epub 2010 Jan 21
Abstract
 
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 Feb 22
Abstract
 
Loh KM and Lim B* "Recreating pluripotency?" Cell Stem Cell 2010 Aug 6 ; 7(2) : 137-9
Abstract
 
Xie Huangming, Lim Bing, Lodish Harvey F "MicroRNAs Induced during Adipogenesis That Accelerate Fat Cell Development Are Downregulated in Obesity." Diabetes 2009 Feb 2 ; :
Abstract
 
Feng Bo, Jiang Jianming, Kraus Petra, Ng Jia-Hui, Heng Jian-Chien Dominic, Chan Yun-Shen, Yaw Lai-Ping, Zhang Weiwei, Loh Yuin-Han, Han Jianyong, Vega Vinsensius B, Cacheux-Rataboul Valere, Lim Bing, Lufkin Thomas, Ng Huck-Hui "Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb." Nat. Cell Biol. 2009 Feb ; 11(2) : 197-203
Abstract
 
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 Apr 1 ; 23(7) : 862-76 Epub 2009 Mar 17
Abstract
 
Liu Tong Ming, Wu Ying Nan, Guo Xi Min, James Hoi Po Hui, Lee Eng Hin, Lim Bing "Effects of Ectopic Nanog and Oct4 Overexpression on Mesenchymal Stem Cells." Stem Cells Dev. 2008 Dec 22 ; :
Abstract
 
Tay Yvonne M-S, Tam Wai-Leong, Ang Yen-Sin, Gaughwin Philip M, Yang Henry, Wang Weijia, Liu Rubing, George Joshy, Ng Huck-Hui, Perera Ranjan J, Lufkin Thomas, Rigoutsos Isidore, Thomson Andrew M, Lim Bing "MicroRNA-134 modulates the differentiation of mouse embryonic stem cells, where it causes post-transcriptional attenuation of Nanog and LRH1." Stem Cells 2008 Jan ; 26(1) : 17-29
Abstract
 
Tam Wai-Leong, Lim Chin Yan, Han Jianyong, Zhang Jinqiu, Ang Yen-Sin, Ng Huck-Hui, Yang Henry, Lim Bing "T-cell factor 3 regulates embryonic stem cell pluripotency and self-renewal by the transcriptional control of multiple lineage pathways." Stem Cells 2008 Aug ; 26(8) : 2019-31
Abstract
 
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 Nov 6 ; 3(5) : 543-54 Epub 2008 Sep 18
Abstract
 
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 Oct 23 ; 455(7216) : 1124-8 Epub 2008 Sep 17
Abstract
 
Soh Boon Seng, Song Chun Meng, Vallier Ludovic, Li Pin, Choong Cleo, Yeo Boon Huat, Lim Elaine Hsuen, Pedersen Roger A, Yang Henry He, Rao Mahendra, Lim Bing "Pleiotrophin enhances clonal growth and long-term expansion of human embryonic stem cells." Stem Cells 2007 Dec ; 25(12) : 3029-37
Abstract
 
Miranda KC, Huynh T, Tay Y, Ang YS, Tam WL, Thomson AM, Lim B*, Rigoutsos I* "A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes." Cell 2006 Sep 22 ; 126(6) : 1203-17
Abstract
 
Zhang J, Tam WL, Tong GQ, Wu Q, Chan HY, Soh BS, Lou Y, Yang J, Ma Y, Chai L, Ng HH, Lufkin T, Robson P, Lim B* "Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1." Nat Cell Biol 2006 Oct ; 8(10) : 1114-23 Epub 2006 Sep 17
Abstract
 
Kocabas Arif Murat, Crosby Javier, Ross Pablo J, Otu Hasan H, Beyhan Zeki, Can Handan, Tam Wai-Leong, Rosa Guilherme J M, Halgren Robert G, Lim Bing*, Fernandez Emilio*, Cibelli Jose Bernardo* "The transcriptome of human oocytes." Proc. Natl. Acad. Sci. U.S.A. 2006 Sep 19 ; 103(38) : 14027-32
Abstract
 
Loh Yuin-Han, Wu Qiang, Chew Joon-Lin, Vega Vinsensius B, Zhang Weiwei, Chen Xi, Bourque Guillaume, George Joshy, Leong Bernard, Liu Jun, Wong Kee-Yew, Sung Ken W, Lee Charlie W H, Zhao Xiao-Dong, Chiu Kuo-Ping, Lipovich Leonard, Kuznetsov Vladimir A, Robson Paul, Stanton Lawrence W, Wei Chia-Lin, Ruan Yijun, Lim Bing, Ng Huck-Hui "The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells." Nat. Genet. 2006 Apr ; 38(4) : 431-40
Abstract
 
Chia Lin WEI, Miura T, Paul ROBSON, Sai Kiang LIM, Xu XQ, Lee MY, Sanjay GUPTA, Lawrence STANTON, Luo Y, Schmitt J, Thies S, Wang W, Khrebtukova I, Zhou D, Edison Tak-Bun LIU, Yijun RUAN, Rao M, Bing LIM (2005) "Transcriptome profiling of murine and human ES cells reveals divergent paths to maintenance of the stem cell state" Stem Cells 23 166-185
 
 
Que J, Out, H.H, Lian, Q.Z, Libermann, T.A, El Oakley R.M, Bing LIM, Sai Kiang LIM (2005 ) "Rapamycin-sensitive mTOR-mediated translational control is a pivotal component of endothelial differentiation (submitted)"
 
 
Lian, Q.Z, Lye, E, Yeo, KS, Que J, Liu T.M, Tan, E.K.W, Yu, F, Yin Y, El Oakley R.M, Bing LIM, Sai Kiang LIM (2005 ) "A model for directed ESC differentiation: deriving lineage-restricted progenitor cell lines (submitted)"
 
 
Joon-Lin Chew, Yuin-Han Loh, Paul ROBSON, Bing LIM, Ang Yen-Sin, Li Pin, Yeap Leng-Siew, Tam Wai-Leong, Chen Xi, Zhang Wensheng, Huck Hui NG (2005) "Reciprocal Transcriptional Regulation of Pou5f1 and Sox2 Via the Oct4/Sox2 Complex in Embryonic Stem Cells" Molecular & Cellular Biology 25 6031-6046
 
 
Salto-Tellez M, Tan E, Bing LIM (2005) "ARDS in SARS: cytokine mediators and treatment implications" Cytokine 29 92-94
 
 
Tan, E.L.C., Ooi, E.E, Lin Chin Yo, Tan H.C., Ling A.E., Bing LIM, Lawrence STANTON (2004) "Inhibition of SARS coronavirus in vitro with clinically approved anti-viral drugs" Emerg Infect Dis 10 (4) 581-86
 
 
Lisa K. Cherry, Xiaoyu Li, Bing LIM, Lloyd B. Klickstein (2004) "Genome-wide screen identified RhoH as a regulator of lymphpocyte LFA-1" Nature Immunology 5 961-96
 
 
Fortunel NO, Otu HH, Ng HH, Chen J, Mu X, Chevassut T, Li X, Joseph M, Bailey C, Hatzfeld JA, Hatzfeld A, Usta F, Vega VB, Long PM, Libermann TA, Lim B* "Comment on "Stemness: transcriptional profiling of embryonic and adult stem cells" and "A stem cell molecular signature"." Science 2003 Oct 17 ; 302(5644) : 393; author reply 393
Abstract
 
Layer K, Lin G, Nencioni A, Hu W, Schmucker A, Antov AN, Li X, Takamatsu S, Chevassut T, Dower NA, Stang SL, Beier D, Buhlmann J, Bronson RT, Elkon KB, Stone JC, Van Parijs L*, Lim B* "Autoimmunity as the consequence of a spontaneous mutation in Rasgrp1." Immunity 2003 Aug ; 19(2) : 243-55
Abstract
 
Timothy Chevassut, Bing LIM (2003) "Insights into the role of DNA methylation in murine embryonal stem cells using a modified tetracycline-inducible Gene Expression System" (In Press, Oncology Research 2003)
 
 
Fajun Yang, Xiaoyu Li, Manju Sharma, Carl Sasaki, Mark Zarnegar, Dan Lango, Bing LIM, Zijie Sun (2002) "Linking ?-catenin to Androgen Receptor Signaling pathway: Implications in prostate cancer progression ." J Biol Chem 277:11336-11344
 
 
Li X, Xia B, Lu B, Avraham H, Flavell R, Bing LIM (2002) "The hematopoietic-specific GTP-binding proteinRhoH is GTPase-deficient and modulates activities of other RhoGTPases by an inhibitory function" Mol & Cell Biol 22:1158-1171
 
 
Gu H, Klaman LD, Shen J, Fleming T, Wang Y, Pratt JC, Lin G, Bing LIM, Kinet J-P (2001) "Neel BG Essential Role of Gab2 in Allergic Response." Nature 412:186-190
 
 
Cuervo AM, Hu W, Bing LIM, Dice JF (1998) "IkB is a substrate for a selective pathway of lysosomal proteolysis." Mol Biol of Cell 8:1995-2010
 
 
Adra CN, Manor D, Ko J-L, Zhou S, Cerione RA, Bing LIM (1997) "RhoGDI?-A novel GDP-Dissociation Inhibitor for Rho subfamily of GTP binding proteins preferentially" Proc. Natl. Acad. Sci 94: 4279-4284
 
 
Adra CN, Rowley JD, Lelias J-M, Horiuchi T, Koyabashi H, Cuervo AM, Guillemot J-C, Ko J-L, Zhu S C, Bing LIM (1996) "LAPTm5: A novel lysosomal-associated multispanning membrane protein preferentially expressed in hematopoietic cells." Genomics 35: 328-337
 
 
Platko J, Leonard D, Adra CN, Reuben JS, Cerione RA, Bing LIM (1995) "The Carboxyl Terminal Domain of the Rho Subfamily GDP-Dissociation Inhibitor Is Responsible for Functional Specificity." Proc. Natl. Acad. Sci. U.S.A. 92: 2974-2978
 
 
Adra CN, Kobayashi H, Lelias J-M, Kaghad M, Morrisson P, Rowley J, Bing LIM (1994) "Cloning of the cDNA for a hematopoietic specific proteinrelated to Fc?RIB and CD20; evidence for a superfamily of 4-transmembrane spanning proteins" Proc. Natl. Acad. Aci. U.S.A 91:10178-10182
 
 
Lelias J M, Adra CN, Wulf GM, Khagad M, Caput D, Bing LIM (1993) "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. 90:1479-1483.
 
 
Wulf GM, Adra CN, Bing LIM (1993) "Inhibition of Hematopoietic Development from Embryonic Stem cells by Antisense-vav RNA." EMBO Journal 12:5065-5074
 
 
Bing LIM, Apperley JF, Orkin SH, Williams DA (1989) "Long-term expression of human Adenosine Deaminase in Mice Transplanted with Retroviral Vector-Infected Hematopoietic Stem Cells." Proc. Natl. Acad. Sci. 86:8892-8896
 
 
Bing LIM, Williams DA, Orkin SH (1987) "Expression of human adenosine deaminase in murine hematopoietic stem cells." Mol. Cell. Biol. 7:3459-3465.