We all arose from one fertilized egg cell; in the precise and correct ratios, ~50 trillion cells arose from the division of one primitive cell. This requires incredible balance- too many divisions of the same clone equals cancer. The division of primitive cells that reside in human tissues must also strike this balance. By studying how molecules work together during the division of these cells, my group hopes to better detect, monitor, and treat the childhood and hereditary cancers that arise as a result of too many cell divisions and inflict 1,400 kids and 2,200 young adults each year in Canada.
Pathogenic BRCA1 variants disrupt PLK1-regulation of mitotic spindle orientation
Z He, R Ghorayeb, S Tan, K Chen, AC Lorentzian, J Bottyan, SM Musheer Aalam, MA Pujana, PF Lange, N Kannan, CJ Eaves, CA Maxwell
Modification of BRCA1-associated breast cancer risk by HMMR overexpression
F Mateo*, Z He*, L Mei*, G Ruiz de Garibay, C Herranz, N Garcia, A Lorentzian, A Baiges, E Blommaert, A Gomez, O Mirallas, A Garrido-Utrilla, L Palomero, R Espin, AI Extremera, MT Soler-Monso, A Petit, R Li, J Brunet, K Chen, S Tan, CJ Eaves, C McCloskey, R Hakem, R Khokha, PF Lange, C Lazaro, CA Maxwell** and MA Pujana** **senior authors
Proteogenomic analysis identifies the persistence of targetable lesions and proteomes through disease evolution in pediatric acute lymphoblastic leukemia
AC Lorentzian, M Guo, EK Ergin, NM Akella, N Rolf, C J Lim, GSD Reid, CA Maxwell** and PF Lange** **senior authors
A Model of Differential Mammary Growth Initiation by Stat3 and Asymmetric Integrin-a6 Inheritance.
Morris EJ**, Gillespie JA, Maxwell CA** and Dedhar S** **senior authors
FAM83D directs protein kinase CK1a to the mitotic spindle for proper spindle positioning.
Fulcher LJ, He Z, Mei L, Macartney TJ, Wood NT, Prescott AR, Whigham AJ, Varghese J, Gourlay R, Ball G, Clarke R, Campbell DG, Maxwell CA, Sapkota GP
Tumor Variant Identification That Accounts for the Unique Molecular Landscape of Pediatric Malignancies.
Jnci Cancer Spectrum
Lorentzian A, Biegel JA, Ostrow DG, Rolf N, Liu CC, Rassekh SR, Deyell RJ, Triche T, Schultz KR, Rozmus J, Reid GSD, Lim CJ, Lange PF** and Maxwell CA** **senior authors
The non-motor adaptor HMMR dampens Eg5-mediated forces to preserve the kinetics and integrity of chromosome segregation.
Molecular biology of the cell
Chen H, Connell M, Mei L, Reid GSD, Maxwell CA
HMMR acts in the PLK1-dependent spindle positioning pathway and supports neural development.
Connell M*, Chen H*, Jiang J, Kuan CW, Fotovati A, Chu TL , He Z, Lengyell TC, Li H, Kroll T, Li AM, Goldowitz D, Frappart L, Ploubidou A, Patel MS, Maxwell CA
Cell Cycle-Dependent Tumor Engraftment and Migration Are Enabled by Aurora-A.
Molecular cancer research : MCR
Chu TLH*, Connell M*, Zhou L, He Z, Won J, Chen H, Rahavi SMR, Mohan P, Nemirovsky O, Fotovati A, Pujana MA, Reid GSD, Nielsen TO, Pante N, Maxwell CA
Centrosome Amplification Is a Potential Molecular Target in Paediatric Acute Lymphoblastic Leukemia
Meiyun Guo and Jenna Rever and Phuong N. U. Nguyen and Neha M. Akella and Gregor S. D. Reid and Christopher A. Maxwell
A cross-standardized flow cytometry platform to assess phenotypic stability in B-ALL xenografts.
Cytometry. Part A : the journal of the International Society for Analytical Cytology
Rolf N, Liu LYT, Tsang A, Lange PF, Lim CJ, Maxwell CA, Vercauteren SM, Reid GSD
PDX models reflect the proteome landscape of pediatric acute lymphoblastic leukemia but divert in select pathways.
Journal of experimental & clinical cancer research : CR
Hyaluronan Mediated Motility Receptor (HMMR) Encodes an Evolutionarily Conserved Homeostasis, Mitosis, and Meiosis Regulator Rather than a Hyaluronan Receptor
Zhengcheng He and Lin Mei and Marisa Connell and Chris Maxwell
CD44-mediated hyaluronan binding marks proliferating hematopoietic progenitor cells and promotes bone marrow engraftment.
Lee-Sayer SSM, Dougan MN, Cooper J, Sanderson L, Dosanjh M, Maxwell CA, Johnson P
Hyaluronan-binding by CD44 reduces the memory potential of activated murine CD8 T cells.
European journal of immunology
Lee-Sayer SSM, Maeshima N, Dougan MN, Dahiya A, Arif AA, Dosanjh M, Maxwell CA, Johnson P
BRCA1 controls the cell division axis and governs ploidy and phenotype in human mammary cells.
He Z*, Kannan N*, Nemirovsky O, Chen H, Connell M, Taylor B, Jiang J, Pilarski LM, Fleisch MC, Niederacher D, Pujana MA, Eaves CJ** and Maxwell CA** **senior authors
Designing a broad-spectrum integrative approach for cancer prevention and treatment.
Seminars in cancer biology
Block KI and Gyllenhaal C and Lowe L and Amedei A and Amin ARMR and Amin A and Aquilano K and Arbiser J and Arreola A and Arzumanyan A and Ashraf SS and Azmi AS and Benencia F and Zollo M
Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition.
Seminars in cancer biology
Ferguson LR and Chen H and Collins AR and Connell M and Damia G and Dasgupta S and Malhotra M and Meeker AK and Amedei A and Amin A and Ashraf SS and Aquilano K and Azmi AS and Bhakta D and Maxwell CA
Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers.
Blanco I and Kuchenbaecker K and Cuadras D and Wang X and Barrowdale D and de Garibay GR and Librado P and Sánchez-Gracia A and Rozas J and Bonifaci N and McGuffog L and Pankratz VS and Pujana MA
YB-1 transforms human mammary epithelial cells through chromatin remodeling leading to the development of basal-like breast cancer.
Stem cells (Dayton, Ohio)
Davies AH and Reipas KM and Pambid MR and Berns R and Stratford AL and Fotovati A and Firmino N and Astanehe A and Hu K and Maxwell C and Mills GB and Dunn SE
Spatial regulation of Aurora A activity during mitotic spindle assembly requires RHAMM to correctly localize TPX2.
Cell cycle (Georgetown, Tex.)
Chen H and Mohan P and Jiang J and Nemirovsky O and He D and Fleisch MC and Niederacher D and Pilarski LM and Lim CJ and Maxwell CA
Tubers from patients with tuberous sclerosis complex are characterized by changes in microtubule biology through ROCK2 signalling.
The Journal of pathology
Ferrer I and Mohan P and Chen H and Castellsague J and Gómez-Baldó L and Carmona M and García N and Aguilar H and Jiang J and Skowron M and Nellist M and Ampuero I and Russi A and Pujana MA
The Generation, Detection, and Prevention of Genomic Instability During Cancer Progression and Metastasis
Genomic Instability and Cancer Metastasis
Helen Chen and Christopher Maxwell and Marisa Connell
The cytoskeletal protein RHAMM and ERK1/2 activity maintain the pluripotency of murine embryonic stem cells.
Jiang J and Mohan P and Maxwell CA
Genomic imbalance of HMMR/RHAMM regulates the sensitivity and response of malignant peripheral nerve sheath tumour cells to aurora kinase inhibition.
Mohan P and Castellsague J and Jiang J and Allen K and Chen H and Nemirovsky O and Spyra M and Hu K and Kluwe L and Pujana MA and Villanueva A and Mautner VF and Keats JJ and Dunn SE and Maxwell CA
Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer.
Maxwell CA and Benítez J and Gómez-Baldó L and Osorio A and Bonifaci N and Fernández-Ramires R and Costes SV and Guinó E and Chen H and Evans GJ and Mohan P and Català I and Petit A and Pujana MA
Exploring the link between MORF4L1 and risk of breast cancer.
Breast cancer research : BCR
Martrat G and Maxwell CM and Tominaga E and Porta-de-la-Riva M and Bonifaci N and Gómez-Baldó L and Bogliolo M and Lázaro C and Blanco I and Brunet J and Aguilar H and Pujana MA
YB-1 evokes susceptibility to cancer through cytokinesis failure, mitotic dysfunction and HER2 amplification.
Davies AH and Barrett I and Pambid MR and Hu K and Stratford AL and Freeman S and Berquin IM and Pelech S and Hieter P and Maxwell C and Dunn SE
Targeting tumour-initiating cells to improve the cure rates for triple-negative breast cancer.
Expert reviews in molecular medicine
Stratford AL and Reipas K and Maxwell C and Dunn SE
Multifunctional proteins bridge mitosis with motility and cancer with inflammation and arthritis.
Jiang J and Casalegno-Garduno R and Chen H and Schmitt A and Schmitt M and Maxwell CA
TACC3-TSC2 maintains nuclear envelope structure and controls cell division.
Cell cycle (Georgetown, Tex.)
Gómez-Baldó L and Schmidt S and Maxwell CA and Bonifaci N and Gabaldón T and Vidalain PO and Senapedis W and Kletke A and Rosing M and Barnekow A and Rottapel R and Capellá G and Pujana MA
Biological convergence of cancer signatures.
Solé X and Bonifaci N and López-Bigas N and Berenguer A and Hernández P and Reina O and Maxwell CA and Aguilar H and Urruticoechea A and de Sanjosé S and Comellas F and Capellá G and Pujana MA
Targeted and nontargeted effects of ionizing radiation that impact genomic instability.
Maxwell CA and Fleisch MC and Costes SV and Erickson AC and Boissière A and Gupta R and Ravani SA and Parvin B and Barcellos-Hoff MH
Aurora A kinase RNAi and small molecule inhibition of Aurora kinases with VE-465 induce apoptotic death in multiple myeloma cells.
Leukemia & lymphoma
Evans R and Naber C and Steffler T and Checkland T and Keats J and Maxwell C and Perry T and Chau H and Belch A and Pilarski L and Reiman T
Genetic and genomic analysis modeling of germline c-MYC overexpression and cancer susceptibility.
Solé X and Hernández P and de Heredia ML and Armengol L and Rodríguez-Santiago B and Gómez L and Maxwell CA and Aguiló F and Condom E and Abril J and Pérez-Jurado L and Estivill X and Pujana MA
Genetic interactions: the missing links for a better understanding of cancer susceptibility, progression and treatment.
Maxwell CA and Moreno V and Solé X and Gómez L and Hernández P and Urruticoechea A and Pujana MA
The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for multiple myeloma.
British journal of haematology
Evans RP and Naber C and Steffler T and Checkland T and Maxwell CA and Keats JJ and Belch AR and Pilarski LM and Lai R and Reiman T
Targeting aurora kinases as therapy in multiple myeloma.
Shi Y and Reiman T and Li W and Maxwell CA and Sen S and Pilarski L and Daniels TR and Penichet ML and Feldman R and Lichtenstein A
Geometric approach to segmentation and protein localization in cell culture assays.
Journal of microscopy
Raman S and Maxwell CA and Barcellos-Hoff MH and Parvin B
Intensity-based signal separation algorithm for accurate quantification of clustered centrosomes in tissue sections.
Microscopy research and technique
Fleisch MC and Maxwell CA and Kuper CK and Brown ET and Barcellos-Hoff MH and Costes SV
The pleiotropic roles of transforming growth factor beta in homeostasis and carcinogenesis of endocrine organs.
Fleisch MC and Maxwell CA and Barcellos-Hoff MH
Hyaluronan and hyaluronan synthases: potential therapeutic targets in cancer.
Current drug targets. Cardiovascular & haematological disorders
Adamia S and Maxwell CA and Pilarski LM
Receptor for hyaluronan-mediated motility correlates with centrosome abnormalities in multiple myeloma and maintains mitotic integrity.
Maxwell CA and Keats JJ and Belch AR and Pilarski LM and Reiman T
Overexpression of transcripts originating from the MMSET locus characterizes all t(4;14)(p16;q32)-positive multiple myeloma patients.
Keats JJ and Maxwell CA and Taylor BJ and Hendzel MJ and Chesi M and Bergsagel PL and Larratt LM and Mant MJ and Reiman T and Belch AR and Pilarski LM
RHAMM expression and isoform balance predict aggressive disease and poor survival in multiple myeloma.
Maxwell CA and Rasmussen E and Zhan F and Keats JJ and Adamia S and Strachan E and Crainie M and Walker R and Belch AR and Pilarski LM and Barlogie B and Shaughnessy J and Reiman T
Fluorescence imaging of multiple myeloma cells in a clinically relevant SCID/NOD in vivo model: biologic and clinical implications.
Mitsiades CS and Mitsiades NS and Bronson RT and Chauhan D and Munshi N and Treon SP and Maxwell CA and Pilarski L and Hideshima T and Hoffman RM and Anderson KC
RHAMM is a centrosomal protein that interacts with dynein and maintains spindle pole stability.
Molecular biology of the cell
Maxwell CA and Keats JJ and Crainie M and Sun X and Yen T and Shibuya E and Hendzel M and Chan G and Pilarski LM
In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression.
Keats JJ and Reiman T and Maxwell CA and Taylor BJ and Larratt LM and Mant MJ and Belch AR and Pilarski LM
The integration of tissue structure and nuclear function.
Biochemistry and cell biology = Biochimie et biologie cellulaire
Maxwell CA and Hendzel MJ
The objectives for my research program are to more completely understand cell division at a molecular level and apply that knowledge to the study of cells that maintain the growth and development of the human brain and breast. We focus on a small set of key genes and study how their products are involved in human development and cancer using a variety of systems, including cells that grow indefinitely in the lab, mice, flies, and human tissues from both healthy and diseased individuals.Grants
The Maxwell lab is a member of the Michael Cuccione Childhood Cancer Research program. We have received research funding support from the following organizations
Avon Foundation, Canadian Breast Cancer Foundation, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, and the Michael Cuccione Foundation. We are very grateful for their support.Honours & Awards
New Investigator, NIC category, CIHRResearch Group Members
Esther Choi, Clinical Research Associate, Ethics and Regulatory
Patrick Diaz, Lead Clinical Research Associate
Leili Ghazizadeh, Research Staff
Ryan Ghorayeb, Graduate Student
Amanda Lorentzian, Graduate student
Lin Mei, PhD Student
Jenna Rever, Research Technician
Agam Sodhi, co op clinical research assistant
Jeong Min Son, Co-op Research Assistant
Brenda Tse, Research Coordinator
Evan Zhou, Research Assistant (Tech 3)