Associate ProfessorPhD, University of British Columbia
Toronto Medical Discovery Tower
101 College Street, Room 12-305
Toronto, Ontario M5G 1L7
Phone: (416) 581-7868
Lab Phone: (416) 581-7869
Email Dr. Laurie Ailles
At A Glance:
- Focus of the lab includes cancer stem cells, cancer-associated fibroblasts, clonal heterogeneity and epigenetics
- All work is done using primary patient-derived cancer tissue specimens, as well as patient-derived primary cultures and xenografts
- Diseases studied include head and neck squamous cell carcinoma, high-grade serous ovarian cancer and clear cell renal cell carcinoma
- We have established a “living biobank” of patient-derived xenografts that can be used to assay cancer stem cells, evaluate drug responses and development of drug resistance, and to perform a wide range of novel, clinically relevant studies.
- We collaborate extensively with other labs, clinicians and clinician scientists
Laurie Ailles is a Scientist at the Princess Margaret Cancer Centre, University Health Network, and Assistant Professor in the Dept. of Medical Biophysics at the University of Toronto. Dr. Ailles earned a Master’s Degree in Pathology from Queen’s University (Kingston, ON, Canada) and a Ph.D. Degree in Genetics from the University of British Columbia. She then went on to a postdoctoral fellowship in Turin, Italy, in the laboratory of Dr. Luigi Naldini, followed by a second post-doc at Stanford University in the laboratory of Dr. Irv Weissman. Dr. Ailles started her own laboratory in Toronto in 2008.
Dr. Ailles and her team are now focusing on two major research areas:
1. Intra-tumoral heterogeneity.
One focus is the identification and characterization of tumor-initiating cells (TICs) in solid tumors and the relationship between TICs and clonal evolution. We also study the role of cancer-associated fibroblasts in promoting malignant behaviors such as stemness and invasion. The cancers studied are head and neck squamous cell carcinoma, high-grade serous ovarian cancer, and clear cell renal cell carcinoma.
2. Epigenetics in clear cell renal cell carcinoma (ccRCC).
We are using primary patient-derived cultures and xenografts to gain a deep understanding of the epigenetic deregulation occurring in ccRCC, including identification of downstream effects on target genes and pathways and identification of small molecules with rapid clinical translational potential.
Dr. Ailles’ most recent scientific contributions include the identification of tumor-initiating cell populations in head and neck and ovarian cancer, and development of novel methods for generating patient-derived cultures from ccRCC patients with high efficiency.
Optimization of HSC transduction by lentiviral vectors. In Luigi Naldini’s lab in Torino, Italy, I contributed to the discovery that the addition of the HIV-1 polypurine tract to the lentiviral vector backbone greatly improved the efficiency of nuclear translocation of the pre-integration complex, and thus of lentiviral vector integration into non-dividing cells (published in Nature Genetics, 2000). This vector design is now used throughout the scientific community for a wide range of applications. In addition, I was the first to demonstrate by clonal analysis that the cells being transduced by lentiviral vectors were true self-renewing HSC, based on the ability of a single transduced clone to repopulate both primary and secondary NOD/SCID mice (published in Molecular Therapy, 2002).
Development of Wnt reporter lentiviral vectors. In Irving Weissman’s lab at Stanford University, I developed lentiviral vector reporters of activated Wnt signaling. These vectors contributed to two important publications from the Weissman lab; one showing that the Wnt pathway plays a role in mediating hematopoietic stem cell self-renewal (published in Nature, 2003), and one showing that the abnormal activation of the Wnt pathway in the myeloid progenitor compartment of chronic myeloid leukemia (CML) patients leads to their progession to acute phase of the disease (published in NEJM, 2004). The latter was the first demonstration (as well as a mechanism) of a normally non-self-renewing cell acquiring the properties of self-renewal, and leading to an aggressive malignant phenotype.
Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. I identified a subset of cells in human head and neck squamous cell carcinomas (HNSCC) that possess the unique properties of cancer stem cells (published in PNAS, 2007), and form unique histological microdomains that may provide a prognostic indicator for HNSCC patients. Identification of this subset of cells will allow further characterization at the molecular level, and should ultimately lead to cancer initiating cell-targeted therapies for HNSCC. More recently, we demonstrated that the frequency of cells with the phenotype of CICs correlates with disease-free survival (published in Head and Neck, 2012), demonstrating the clinical importance of CICs in this disease.
Identification of ovarian cancer initiating cells, and demonstration of their phenotypic heterogeneity and instability. In collaboration with the Neel Lab, we identified CD133 as a marker that allows isolation of cancer-initiating cells from several primary serous ovarian cancer (SOC) cases. However, in other cases, substantial TIC activity is found in both the CD133+ and CD133- fractions, whereas still other cases have exclusively CD133- TIC. Furthermore, the TIC phenotype can change in xenografts: primary tumors in which all TIC are CD133+ can give rise to xenografts that contain substantial numbers of CD133- TIC. Our results highlighted the need for quantitative rigor in the evaluation of TICs and for caution when using passaged xenografts for such studies. Furthermore, although our data suggest that while SOC conforms to the cancer stem cell hypothesis, the heterogeneity of the TIC phenotype may complicate its clinical application (Published in PNAS in 2011).
Development of a novel high-throughput flow cytometry platform for cell surface profiling. A platform for the systematic profiling of >360 cell surface proteins was developed and demonstrated to provide a sensitive, quantitative and highly reproducible resource for biomarker discovery, molecular classification of cancers, or identification of novel lineage-specific or stem cell markers (published in PLoS One in 2014).
List of Key Publications:Link to Pubmed Publications
Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA. 104:973-8, 2007. PMID: 17210912
Stewart, JM, Shaw PA, Gedye C, Bernardini M, Neel BJ, Ailles LE. Phenotypic Heterogeneity and Instability of Human Ovarian Tumor-Initiating Cells. Proc Natl Acad Sci USA, 108:6468-73, 2011. PMID: 21451132
Joshua B, Kaplan MJ, Doweck I, Pai R, Weissman IL, Prince ME, Ailles L. The Frequency of Cells Expressing CD44, a Head and Neck Cancer Stem Cell Marker, Correlates with Tumor Aggressiveness. Head and Neck, 34:42-9, 2012. PMID: 21322081
Significance Analysis of Prognostic Signatures. Beck AH, Knoblauch NW, Hefti MM, Kaplan J, Schnitt SJ, Culhane AC, Schroeder MS, Risch T, Quackenbush J, Haibe-Kains B. PLoS Comput Biol. 2013 Jan;9(1):e1002875. PMID: 23365551
Murillo-Sauca O, Chung MK, Shin JH, Karamboulas C, Kwok S, Jung YH, Oakley R, Tysome JR, Farnebo LO, Kaplan MJ, Sirjani D, Divi V, Holsinger CF, Tomeh C, Nichols A, Le QT, Colevas D, Kong CS, Uppaluri R, Lewis JS Jr., Ailles LE, and Sunwoo JB. CD271 is a functional and targetable marker of tumor-initiating cells in head and neck squamous cell carcinoma. Oncotarget, 5:6854-66, 2014. PMID: 25149537
Gedye C, Hussain A, Paterson J, Smrke H, Saini H, Sirskyj D, Pereira K, Lobo N, Stewart J, Go C, Ho J, Medrano M, Hyatt E, Yuan J, Lauriault S, Kondratyev M, van den Beucken T, Jewett M, Dirks P, Guidos CJ, Danska J, Wang J, Wouters B, Neel B, Rottapel R, Ailles LE. Cell surface profiling using high-throughput flow cytometry: a platform for biomarker discovery and analysis of cellular heterogeneity. PLOS ONE, 9(8):e105602, 2014. PMID: 25170899
Apostoli AJ, Ailles L. Clonal evolution and tumor-initiating cells: New dimensions in cancer patient treatment. Crit Rev Clin Lab Sci, Epub ahead of print, 2015. PMID: 26397062
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