My research is aimed at understanding the molecular mechanisms governing cell adhesion and motility, in particular those involving white blood cell function in normal as well as in pathologic outcomes.

Circulating white blood cells represent the immune system’s front-line defense against infection. The successful and accurate targeting of white blood cells to inflamed tissues is facilitated by cell adhesion receptor proteins expressed on the surface of these cells. However, aberrant function of these receptor proteins and the cellular signals that regulate them can lead to diseases of the immune system, including leukemia, lymphoma and autoimmunity.

My laboratory is focused on understanding the differences in cellular signalling between healthy and diseased cells in order to explore and evaluate novel signalling targets for therapeutic intervention in blood diseases. We employ a multi-disciplinary approach that encompasses cell biology, protein biochemistry, molecular biology and immunology.


Autocrine IL-6/STAT3 signaling aids development of acquired drug resistance in Group 3 medulloblastoma
Cell Death & Disease
Lakshana Sreenivasan and Hui Wang and Shyong Quin Yap and Pascal Leclair and Anthony Tam and Chinten James Lim
DOI: 10.1038/s41419-020-03241-y

Switching Cyclic Nucleotide-Selective Activation of Cyclic Adenosine Monophosphate-Dependent Protein Kinase Holoenzyme Reveals Distinct Roles of Tandem Cyclic Nucleotide-Binding Domains
ACS Chemical Biology
Daniel He and Robin Lorenz and Choel Kim and Friedrich W. Herberg and Chinten James Lim
DOI: 10.1021/acschembio.7b00732

CD47-Independent Effects Mediated by the TSP-Derived 4N1K Peptide.
PloS one
DOI: 10.1371/journal.pone.0098358

Two modes of integrin activation form a binary molecular switch in adhesion maturation
Molecular Biology of the Cell
DOI: 10.1091/mbc.E12-09-0695

The membrane-proximal kxgffkr motif of a-integrin mediates chemoresistance
Molecular and Cellular Biology
DOI: 10.1128/MCB.00580-13

Integrins and ERp57 Coordinate to Regulate Cell Surface Calreticulin in Immunogenic Cell Death
Frontiers in Oncology
DOI: 10.3389/fonc.2019.00411

a4 Integrins are Type I cAMP-dependent protein kinase-anchoring proteins
Nature Cell Biology
DOI: 10.1038/ncb1561

CD47-ligation induced cell death in T-acute lymphoblastic leukemia
Cell Death & Disease
Pascal Leclair and Chi-Chao Liu and Mahdis Monajemi and Gregor S. Reid and Laura M. Sly and Chinten James Lim
DOI: 10.1038/s41419-018-0601-2

Integrin-mediated Protein Kinase A Activation at the Leading Edge of Migrating Cells
Molecular Biology of the Cell
DOI: 10.1091/mbc.E08-06-0564

a-Integrin expression and function modulates presentation of cell surface calreticulin
Cell Death Dis
DOI: 10.1038/cddis.2016.176

PDX models reflect the proteome landscape of pediatric acute lymphoblastic leukemia but divert in select pathways
Journal of Experimental & Clinical Cancer Research
Anuli C. Uzozie and Enes K. Ergin and Nina Rolf and Janice Tsui and Amanda Lorentzian and Samuel S. H. Weng and Lorenz Nierves and Theodore G. Smith and C. James Lim and Christopher A. Maxwell and Gregor S. D. Reid and Philipp F. Lange
DOI: 10.1186/s13046-021-01835-8

FAM13A as potential therapeutic target in modulating TGF-beta-induced airway tissue remodeling in COPD
American Journal of Physiology-Lung Cellular and Molecular Physiology
Anthony Tam and Pascal Leclair and Ling Vicky Li and Chen X Yang and Xuan Li and Dominik Witzigmann and Jayesh A Kulkarni and Tillie-Louise Hackett and Delbert R. Dorscheid and Gurpreet K Singhera and James C. Hogg and Pieter R Cullis and Don D. Sin and Chinten James Lim
DOI: 10.1152/ajplung.00477.2020

A cross-standardized flow cytometry platform to assess phenotypic stability in precursor B-cell acute lymphoblastic leukemia (B-ALL) xenografts
Cytometry Part A
Nina Rolf and Lorraine Y. T. Liu and Angela Tsang and Philipp F. Lange and Chinten James Lim and Christopher A. Maxwell and Suzanne M. Vercauteren and Gregor S. D. Reid
DOI: 10.1002/cyto.a.24473

CD47 (Cluster of differentiation 47): an anti-phagocytic receptor with a multitude of signaling functions
Animal Cells and Systems
Pascal Leclair and Chinten James Lim
DOI: 10.1080/19768354.2020.1818618

Co-culture of induced pluripotent stem cells with cardiomyocytes is sufficient to promote their differentiation into cardiomyocytes
Axel J. Chu and Eric Jiahua Zhao and Mu Chiao and Chinten James Lim
DOI: 10.1371/journal.pone.0230966

Peptide analogues PKHB1 and 4N1K induce cell death through CD47-independent mechanisms
Cancer Science
Pascal Leclair and Min Jung Kim and Chinten James Lim
DOI: 10.1111/cas.14310

Tailoring the homing capacity of human Tregs for directed migration to sites of Th1-inflammation or intestinal regions
American Journal of Transplantation
DOI: 10.1111/ajt.14936

Reactive oxygen species stress increases accumulation of tyrosyl-DNA phsosphodiesterase 1 within mitochondria
Scientific Reports
Hok Khim Fam and Kunho Choi and Lauren Fougner and Chinten James Lim and Cornelius F. Boerkoel
DOI: 10.1038/s41598-018-22547-8

Tumor Variant Identification That Accounts for the Unique Molecular Landscape of Pediatric Malignancies
JNCI Cancer Spectrum
DOI: 10.1093/jncics/pky079

Combination therapy with proteasome inhibitors and TLR agonists enhances tumour cell death and IL-1ß production
Cell Death & Disease
Anthony C Tang and Seyed M Rahavi and Shan-Yu Fung and Henry Y Lu and Hong Yang and Chinten J Lim and Gregor S Reid and Stuart E Turvey
DOI: 10.1038/s41419-017-0194-1

A magnetically actuated cellular strain assessment tool for quantitative analysis of strain induced cellular reorientation and actin alignment
Rev. Sci. Instrum.
F. Khademolhosseini and C.-C. Liu and C. J. Lim and M. Chiao
DOI: 10.1063/1.4960567

Magnetically actuated microstructured surfaces can actively modify cell migration behaviour
Biomedical Microdevices
DOI: 10.1007/s10544-016-0033-7

Janus films with stretchable and waterproof properties for wound care and drug delivery applications
RSC Advances
Ethan Lee and Hongbin Zhang and John K. Jackson and Chinten James Lim and Mu Chiao
DOI: 10.1039/C6RA16232K

Janus films with stretchable and waterproof properties for wound care and drug delivery applications
RSC Advances
DOI: 10.1039/c6ra16232k

Application of periodic loads on cells from magnetic micropillar arrays impedes cellular migration
2015 28th IEEE International Conference on Micro Electro Mechanical Systems (MEMS)
Farzad Khademolhosseini and Chi-Chao Liu and Chinten J. Lim and Mu Chiao
DOI: 10.1109/memsys.2015.7051033

Rational design of a PKA-based sensor for cGMP
BMC Pharmacology and Toxicology
Robin Lorenz and Daniel He and Choel Kim and Chinten J Lim and Friedrich W Herberg
DOI: 10.1186/2050-6511-16-s1-a64

Application of periodic loads on cells from magnetic micropillar arrays impedes cellular migration
Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS)
DOI: 10.1109/MEMSYS.2015.7051033

Arginase activity in alternatively activated macrophages protects PI3Kp110 delta deficient mice from dextran sodium sulfate induced intestinal inflammation
European Journal of Immunology
DOI: 10.1002/eji.201343981

Spatial regulation of Aurora A activity during mitotic spindle assembly requires RHAMM to correctly localize TPX2
Cell Cycle
DOI: 10.4161/cc.29270

Protein Tyrosine Phosphatase alpha Phosphotyrosyl-789 Binds BCAR3 To Position Cas for Activation at Integrin-Mediated Focal Adhesions
Molecular and Cellular Biology
DOI: 10.1128/MCB.00214-12

The Conserved Kxgffkr Motif of alpha-Integrin Cytoplasmic Tail Mediates Chemoresistance to Doxorubicin in T-Cell Leukemia

beta Integrin Tyrosine Phosphorylation Is a Conserved Mechanism for Regulating Talin-induced Integrin Activation
Journal of Biological Chemistry
DOI: 10.1074/jbc.M109.061275

RIAM activates integrins by linking talin to Ras GTPase membrane-targeting sequences
Journal of Biological Chemistry
DOI: 10.1074/jbc.M807117200

Slit2-Robo4 signalling promotes vascular stability by blocking Arf6 activity
Nature Cell Biology
DOI: 10.1038/ncb1976

On the yellow brick road to platelet GP IIb-IIIa (Integrin alpha IIb beta 3) activation.

Reconstructing and Deconstructing Agonist-Induced Activation of Integrin aIIbß3
Current Biology
DOI: 10.1016/j.cub.2006.08.035

Assignment of sockeye salmon (Oncorhynchus nerka) to spawning sites using DNA markers
Marine Biotechnology
DOI: 10.1007/s10126-004-4065-z

Loss of the Dictyostelium RasC protein alters vegetative cell size, motility and endocytosis
Experimental Cell Research
DOI: 10.1016/j.yexcr.2005.02.002

Chemoattractant-induced Ras activation during Dictyostelium aggregation
Embo Reports
DOI: 10.1038/sj.embor.7400151

RasC plays a role in transduction of temporal gradient information in the cyclic-AMP wave of Dictyostelium discoideum
Eukaryotic Cell
DOI: 10.1128/EC.3.3.646-662.2004

Cytoskeletal regulation by Dictyostelium Ras subfamily proteins
Journal of Muscle Research and Cell Motility
DOI: 10.1023/A:1024471527153

RasC is required for optimal activation of adenylyl cyclase and Akt/PKB during aggregation
Embo Journal
DOI: 10.1093/emboj/20.16.4490

Efficient detection of DNA polymorphisms by fluorescent RAPD analysis

Production of androgenetic zebrafish (Danio rerio)


Current Projects
Acute lymphoblastic leukemia (ALL) is the most common of pediatric cancers. ALL is caused by excessive proliferation of immature lymphocytes in the bone marrow, and their eventual dissemination to other organs. Acquired chemoresistance remains a serious limitation to the successful chemotherapeutic treatment of pediatric ALL, accounting for 20 per cent of all relapse. One mechanism contributing to chemoresistance is promotion of cell survival signaling mediated by lymphoblast cell adhesion to integrin ligands found in the bone marrow stromal environment.

The a4 integrins are cell adhesion receptors highly expressed in lymphocytes and are required for lymphocyte recruitment at inflammatory sites and engraftment in the bone marrow stroma. As such, dysregulated or aberrant a4 integrin function contributes to blood cancers including leukemias and myelomas. In blood cancers, a4-ligand interaction facilitates dissemination of tumor cells or contributes to the development of chemotherapeutic resistance and subsequent tumor relapse. Targeting of the a4-ligand interaction via a4-neutralizing antibodies can be an effective therapeutic strategy; however, complete abrogation of a4 function has led to the potentially fatal progressive multifocal leukoencephalopathy due to suppression of immuno-surveillance. Thus, novel strategies targeting a4 integrin signaling may be preferable to complete a4 blockade.

The adhesive and signaling function of a4 is mediated via interactions of effector proteins with the a4-cytoplasmic domain (a4-tail). Lymphocyte adhesion to substrate via a4 integrins confers enhanced chemotherapeutic resistance attributable to increased activation of cell survival pathways. We recently characterized a tail-truncated a4 mutant that conferred enhanced chemoresistance in an adhesion-independent manner in T-leukemia cells. The gain of chemoresistance effect does not require the extracellular ligand binding capacities of a4, nor of the contribution of ß1 integrin subunit. We are currently characterizing the proteins that interact with the truncated a4-tail, reasoning that the interaction/s may constitute the switch for activating the pro-survival signaling. We are also elucidating the moelcular mechanism responsible for the integrin adhesion-based promotion of chemoresistance. A detailed understanding of these mechanisms will reveal novel molecular targets for their targeting in abrogating cell adhesion mediated chemoresistance.

We are also attempting to understand the contribution of bone marrow stromal derived signals in activation of lymphocyte integrins, and assessing the outcomes on chemotherapeutic induced apoptosis. In that regard, we are evaluating if integrin activation with and without the accompanying cell adhesion have differential effects on either chemoresistance or drug-induced apoptosis.


The Lim laboratory is a member of the Michael Cuccione Childhood Cancer Research Program of BC Children's Hospital

Canadian Institutes of Health Research (CIHR) Operating Grant (2021-26)

Honours & Awards

The Leukemia and Lymphoma Society of Canada (LLSC) OG (2010-2012)

CFI/BCKDF – Leaders Opportunity Fund (2010)

The Leukemia and Lymphoma Society (U.S.A.) – Fellow, Career Development Program (2004–07)

Research Group Members

Tariq Bhat, Graduate Student
Madina Kagieva
Theodore Lam, Graduate Student
Pascal Leclair, Research Technician
Ling Li, Graduate Student
Lakshana Sreenivasan, PhD Student
Anthony Tam, Postdoctoral Fellow
Chau Truong, Graduate Student
Brenda Tse, Research Coordinator