Overview

A unifying focus of my laboratory-based research activities at BC Children's Hospital Research Institute is understanding both the desired and adverse effects of chemo and other therapies in pediatric cancers. The Lim laboratory employs a multi-disciplinary approach that encompasses cell biology, protein biochemistry, molecular biology, and immunology.

Publications

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
05/2018

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
12/2020

a-Integrin expression and function modulates presentation of cell surface calreticulin
Cell Death Dis
Liu, C. C. and Leclair, P. and Monajemi, M. and Sly, L. M. and Reid, G. S. and Lim, C. J.
DOI: 10.1038/cddis.2016.176
2016

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
12/2017

The membrane-proximal kxgffkr motif of a-integrin mediates chemoresistance
Molecular and Cellular Biology
Liu, C.-C. and Leclair, P. and Yap, S.Q. and Lim, C.J.
DOI: 10.1128/MCB.00580-13
2013

Integrins and ERp57 Coordinate to Regulate Cell Surface Calreticulin in Immunogenic Cell Death
Frontiers in Oncology
DOI: 10.3389/fonc.2019.00411
05/2019

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
06/2021

Proteomics and personalized patient-derived xenograft models identify treatment opportunities for a progressive malignancy within a clinically actionable timeframe and change care
Georgina D. Barnabas and Tariq A. Bhat and Verena Goebeler and Pascal Leclair and Nadine Azzam and Nicole Melong and Colleen Anderson and Alexis Gom and Seohee An and Enes K. Ergin and Yaoqing Shen and Andy J. Mungall and Karen L. Mungall and Christopher A. Maxwell and Gregor S.D. Reid and Martin Hirst and Steven Jones and Jennifer A. Chan and Donna L. Senger and Jason N. Berman and Seth J. Parker and Jonathan W. Bush and Caron Strahlendorf and Rebecca J. Deyell and Chinten J. Lim and Philipp F. Lange and PROFYLE Program
DOI: 10.1101/2024.07.04.24309923
07/2024

DDIT4L regulates mitochondrial and innate immune activities in early life
JCI Insight
Christina Michalski and Claire Cheung and Ju Hee Oh and Emma Ackermann and Constantin R. Popescu and Anne-Sophie Archambault and Martin A. Prusinkiewicz and Rachel Da Silva and Abdelilah Majdoubi and Marina Viñeta Paramo and Rui Yang Xu and Frederic Reicherz and Annette E. Patterson and Liam Golding and Ashish Arunkumar Sharma and Chinten J. Lim and Paul C. Orban and Ramon Klein Geltink and Pascal M. Lavoie
DOI: 10.1172/jci.insight.172312
02/2024

Targetable lesions and proteomes predict therapy sensitivity through disease evolution in pediatric acute lymphoblastic leukemia
Nature Communications
Amanda C. Lorentzian and Jenna Rever and Enes K. Ergin and Meiyun Guo and Neha M. Akella and Nina Rolf and C. James Lim and Gregor S. D. Reid and Christopher A. Maxwell and Philipp F. Lange
DOI: 10.1038/s41467-023-42701-9
11/2023

Hedgehog Signaling as a Therapeutic Target for Airway Remodeling and Inflammation in Allergic Asthma
Cells
Anthony Tam and Osei ET and Chung Y. Cheung and Michael R. Hughes and Chen X. Yang and Kelly McNagny and Delbert R. Dorscheid and Gurpreet Singhera and Teal S. Hallstrand and Stephanie Warner and James C. Hogg and Tillie-Louise Hackett and Chinten James Lim and Don Sin
DOI: 10.3390/cells11193016
09/2022

Targeting the gp130/STAT3 Axis Attenuates Tumor Microenvironment Mediated Chemoresistance in Group 3 Medulloblastoma Cells
Cells
Lakshana Sreenivasan and Ling Vicky Li and Pascal Leclair and Chinten James Lim
DOI: 10.3390/cells11030381
01/2022

Inflammatory Immune Responses Trigger Rejection of Allogeneic Fibroblasts Transplanted into Mouse Skin
Cell Transplantation
Ali Farrokhi and MohammadReza Rahavi and Sumin Jo and Reza Jalili and C. James Lim and Aziz Ghahsary and Gregor S. D. Reid
DOI: 10.1177/09636897221113803
01/2022

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
01/2022

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
12/2021

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
09/2020

Co-culture of induced pluripotent stem cells with cardiomyocytes is sufficient to promote their differentiation into cardiomyocytes
PLOS ONE
Axel J. Chu and Eric Jiahua Zhao and Mu Chiao and Chinten James Lim
DOI: 10.1371/journal.pone.0230966
04/2020

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
03/2020

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
01/2019

Tumor Variant Identification That Accounts for the Unique Molecular Landscape of Pediatric Malignancies.
JNCI cancer spectrum
DOI: 10.1093/jncics/pky079
PubMed: 30976750
10/2018

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
03/2018

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
02/2018

A magnetically actuated cellular strain assessment tool for quantitative analysis of strain induced cellular reorientation and actin alignment
Review of Scientific Instruments
F. Khademolhosseini and C.-C. Liu and C. J. Lim and M. Chiao
DOI: 10.1063/1.4960567
08/2016

Magnetically actuated microstructured surfaces can actively modify cell migration behaviour
Biomedical microdevices
Khademolhosseini, F. and Liu, C.-C. and Lim, C.J. and Chiao, M.
DOI: 10.1007/s10544-016-0033-7
2016

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
2016

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)
Khademolhosseini, F. and Liu, C.-C. and Lim, C.J. and Chiao, M.
DOI: 10.1109/MEMSYS.2015.7051033
2015

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
2015

Arginase activity in alternatively activated macrophages protects PI3Kp110d deficient mice from dextran sodium sulfate induced intestinal inflammation
European Journal of Immunology
Weisser, S.B. and Kozicky, L.K. and Brugger, H.K. and Ngoh, E.N. and Cheung, B. and Jen, R. and Menzies, S.C. and Samarakoon, A. and Murray, P.J. and Lim, C.J. and Johnson, P. and Boucher, J.-L. and van Rooijen, N. and Sly, L.M.
DOI: 10.1002/eji.201343981
2014

Spatial regulation of Aurora A activity during mitotic spindle assembly requires RHAMM to correctly localize TPX2
Cell Cycle
Chen, H. and Mohan, P. and Jiang, J. and Nemirovsky, O. and He, D. and Fleisch, M.C. and Niederacher, D. and Pilarski, L.M. and Lim, C.J. and Maxwell, C.A.
DOI: 10.4161/cc.29270
2014

CD47-independent effects mediated by the TSP-derived 4N1K peptide
PLoS ONE
Leclair, P. and Lim, C.J.
DOI: 10.1371/journal.pone.0098358
2014

Two modes of integrin activation form a binary molecular switch in adhesion maturation
Molecular Biology of the Cell
Lee, H.-S. and Anekal, P. and Lim, C.J. and Liu, C.-C. and Ginsberg, M.H.
DOI: 10.1091/mbc.E12-09-0695
2013

The Conserved Kxgffkr Motif of alpha-Integrin Cytoplasmic Tail Mediates Chemoresistance to Doxorubicin in T-Cell Leukemia
Blood
Liu, Chi-Chao and Leclair, Pascal and He, Daniel and Yap, Eva and Lim, Chinten James
2012

Protein tyrosine phosphatase a Phosphotyrosyl-789 binds BCAR3 to position cas for activation at integrin-mediated focal adhesions
Molecular and Cellular Biology
Sun, G. and Cheng, S.Y.S. and Chen, M. and Lim, C.J. and Pallen, C.J.
DOI: 10.1128/MCB.00214-12
2012

RIAM activates integrins by linking talin to Ras GTPase membrane-targeting sequences
Journal of Biological Chemistry
Lee, H.-S. and Lim, C.J. and Puzon-McLaughlin, W. and Shattil, S.J. and Ginsberg, M.H.
DOI: 10.1074/jbc.M807117200
2009

Slit2-Robo4 signalling promotes vascular stability by blocking Arf6 activity
Nature Cell Biology
Jones, C.A. and Nishiya, N. and London, N.R. and Zhu, W. and Sorensen, L.K. and Chan, A.C. and Lim, C.J. and Chen, H. and Zhang, Q. and Schultz, P.G. and Hayallah, A.M. and Thomas, K.R. and Famulok, M. and Zhang, K. and Ginsberg, M.H. and Li, D.Y.
DOI: 10.1038/ncb1976
2009

ß integrin tyrosine phosphorylation is a conserved mechanism for regulating talin-induced integrin activation
Journal of Biological Chemistry
Anthis, N.J. and Haling, J.R. and Oxley, C.L. and Memo, M. and Wegener, K.L. and Lim, C.J. and Ginsberg, M.H. and Campbell, I.D.
DOI: 10.1074/jbc.M109.061275
2009

Integrin-mediated protein kinase a activation at the leading edge of migrating cells
Molecular Biology of the Cell
Lim, C.J. and Kain, K.H. and Tkachenko, E. and Goldfinger, L.E. and Gutierrez, E. and Allen, M.D. and Groisman, A. and Zhang, J. and Ginsberg, M.H.
DOI: 10.1091/mbc.E08-06-0564
2008

a4 Integrins are Type I cAMP-dependent protein kinase-anchoring proteins
Nature Cell Biology
Lim, C.J. and Han, J. and Yousefi, N. and Ma, Y. and Amieux, P.S. and McKnight, G.S. and Taylor, S.S. and Ginsberg, M.H.
DOI: 10.1038/ncb1561
2007

On the yellow brick road to platelet GP IIb-IIIa (Integrin alpha IIb beta 3) activation.
Blood
Watanabe, Naohide and Han, Jaewon and Lim, C. James and Soriani, Alessandra and Puzon-McLaughlin, Wilma and LaFuente, Esther M. and Boussiotis, Vassiliki A. and Ginsberg, Mark H. and Shattil, Sanford J.
2006

Reconstructing and Deconstructing Agonist-Induced Activation of Integrin aIIbß3
Current Biology
Han, J. and Lim, C.J. and Watanabe, N. and Soriani, A. and Ratnikov, B. and Calderwood, D.A. and Puzon-McLaughlin, W. and Lafuente, E.M. and Boussiotis, V.A. and Shattil, S.J. and Ginsberg, MarkH.
DOI: 10.1016/j.cub.2006.08.035
2006

Assignment of sockeye salmon (Oncorhynchus nerka) to spawning sites using DNA markers
Marine Biotechnology
Corley-Smith, G.E. and Wennerberg, L. and Schembri, J.A. and Lim, C.J. and Cooper, K.L. and Brandhorst, B.P.
DOI: 10.1007/s10126-004-4065-z
2005

Loss of the Dictyostelium RasC protein alters vegetative cell size, motility and endocytosis
Experimental Cell Research
Lim, C.J. and Zawadzki, K.A. and Khosla, M. and Secko, D.M. and Spiegelman, G.B. and Weeks, G.
DOI: 10.1016/j.yexcr.2005.02.002
2005

Chemoattractant-induced Ras activation during Dictyostelium aggregation
EMBO Reports
Kae, H. and Lim, C.J. and Spiegelman, G.B. and Weeks, G.
DOI: 10.1038/sj.embor.7400151
2004

RasC plays a role in transduction of temporal gradient information in the cyclic-AMP wave of Dictyostelium discoideum
Eukaryotic Cell
Wessels, D. and Brincks, R. and Kuhl, S. and Stepanovic, V. and Daniels, K.J. and Weeks, G. and Lim, C.J. and Spiegelman, G. and Fuller, D. and Iranfar, N. and Loomis, W.F. and Soll, D.R.
DOI: 10.1128/EC.3.3.646-662.2004
2004

Cytoskeletal regulation by Dictyostelium Ras subfamily proteins
Journal of Muscle Research and Cell Motility
Lim, C.J. and Spiegelman, G.B. and Weeks, G.
DOI: 10.1023/A:1024471527153
2002

RasC is required for optimal activation of adenylyl cyclase and Akt/PKB during aggregation
EMBO Journal
Lim, C.J. and Spiegelman, G.B. and Weeks, G.
DOI: 10.1093/emboj/20.16.4490
2001

Efficient detection of DNA polymorphisms by fluorescent RAPD analysis
Biotechniques
CorleySmith, GE and Lim, CJ and Kalmar, GB and Brandhorst, BP
1997

Production of androgenetic zebrafish (Danio rerio)
Genetics
CorleySmith, GE and Lim, CTJ and Brandhorst, BP
1996

Research

Current Projects
We have several active projects in the following areas:
1. Understanding the molecular basis of cell adhesion receptors and associated proteins in modifying therapeutic response in pediatric acute lymphoblastic leukemia. This work encompasses the cell death and immunomodulatory effects of the integrin-associated ‘eat me’ protein calreticulin, and the ‘don’t eat me’ protein CD47.
2. Interrogating the tumour microenvironmental sources of stimulatory cytokines that promote the aggressive transformation and treatment resistance of the childhood brain tumor, medulloblastoma.
3. Modeling for precision oncology at BCCH. This project is a multi-investigator led initiative that encompasses a bedside-to-bench approach to molecularly characterize a child’s tumor to identify particular vulnerabilities for therapeutic intervention. The Lim lab employs the chick chorioallantoic membrane (CAM) model as for PDX generation and for testing particular drug susceptibilities.

For additional context, applicants are directed to the list of lab publications available here:
https://orcid.org/0000-0001-6381-7585

Grants

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

Cancer Research Society & CIHR Operating Grant (2022-2024)

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

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, PhD Candidate (Lim lab, Research Assistant)
Kailey Cheung, Volunteer
Mahlegha Ghavami, Postdoctoral Fellow
Natasha Kaprelova
Pascal Leclair, Research Technician
Ling Li, Graduate Student
Catherine Park, Undergraduate Student
Ami Truong, Graduate Student
Brenda Tse, Research Coordinator
Katie Tsung
Juliana Vieira, Graduate Student