Assistant Professor, Department of Human Genetics
Phone: (514) 398-1784
740 Dr Penfield Ave, Room 4203
Montréal, Québec, Canada, H3A 0G1
While collaborating on genome characterization of different tumor entities, research in the lab is focused on following topics:
Comprehensive molecular understanding of renal cell carcinoma
Renal cell carcinoma (RCC) is the most common form of kidney tumors. RCC has different subtypes with clear cell (ccRCC; conventional) being the most frequently diagnosed subtype accounting for 75-80% of RCCs. The incidence of RCC is increasing worldwide, but there is no biological marker for routine clinical use. Furthermore, it is essential to identify novel therapies as RCCs are resistant to conventional chemo- and radio-therapy.
We have recently generated comprehensive genome, epigenome and transcriptome landscapes of ccRCC. In an integrative manner, our lab is dissecting these profiles in order to identify molecular aberrations that possess cancer-driving activities. We have also extended our research to characterize molecular aberrations of other subtypes of RCC including papillary and chromophobe tumors, whose genetic abnormalities are less understood.
Post-transcriptional regulatory programs in cancer
In parallel to analyzing (epi)genome patterns, as factors governing gene expression at transcriptional level, we are investigating role of non-coding transcripts including long non-coding RNAs and microRNAs (miRNAs) as well as RNA binding proteins (RBPs) in post-transcriptional deregulation of cancer transcriptome. Specifically, we combine cancer-associated gene expression patterns with regulatory networks of miRNAs and RBPs, and apply quantitative approaches to these profiles in order to predict factors whose aberrant function can explain the abnormal transcriptome of tumor samples. These potentially “master regulators” are then subjected to experimental verification for their driver activities.
Investigating intra-tumoral heterogeneity and its contribution to metastasis
Approaches to stratifying risk or tailoring therapy for individual cancer patients based on the molecular profile of their tumor biopsy are complicated by the existence of genetic heterogeneity (representing distinct populations of cancer cells with different sets of mutations; subclones) both within and across tumors. Furthermore, across tumor sites, genomes of disseminated cancer cells may have similarities at the onset of metastatic disease, but substantial changes in the genetic composition occur spatially and over time, supporting the suggestion that the expansion of aggressive driver clone(s) and the emergence of relevant subclones correlate with development of incurable disease and potential therapeutic resistance. Our lab has optimized protocols of NGS on minutes amount of DNA as well as on DNA isolated from Formalin-fixed, paraffin-embedded (FFPE) samples providing an opportunity to analyze archived primary tumors of patients affected with metastatic or recurrent disease. We analyze the heterogeneous clonal composition of primary and metastatic tumors in order to investigate genomic evolution of metastasis.
- Bailey, MH, Meyerson, WU, Dursi, LJ, Wang, LB, Dong, G, Liang, WW et al.. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples. Nat Commun. 2020;11 (1):4748. doi: 10.1038/s41467-020-18151-y. PubMed PMID:32958763 PubMed Central PMC7505971.
- Li, CH, Prokopec, SD, Sun, RX, Yousif, F, Schmitz, N, PCAWG Tumour Subtypes and Clinical Translation et al.. Sex differences in oncogenic mutational processes. Nat Commun. 2020;11 (1):4330. doi: 10.1038/s41467-020-17359-2. PubMed PMID:32859912 PubMed Central PMC7455744.
- Wang, Y, Park, JYP, Pacis, A, Denroche, RE, Jang, GH, Zhang, A et al.. A Preclinical Trial and Molecularly Annotated Patient Cohort Identify Predictive Biomarkers in Homologous Recombination-deficient Pancreatic Cancer. Clin Cancer Res. 2020;26 (20):5462-5476. doi: 10.1158/1078-0432.CCR-20-1439. PubMed PMID:32816949 .
- Mehvari, S, Larti, F, Hu, H, Fattahi, Z, Beheshtian, M, Abedini, SS et al.. Whole genome sequencing identifies a duplicated region encompassing Xq13.2q13.3 in a large Iranian family with intellectual disability. Mol Genet Genomic Med. 2020; :e1418. doi: 10.1002/mgg3.1418. PubMed PMID:32715656 PubMed Central PMC7549592.
- Saatci, O, Kaymak, A, Raza, U, Ersan, PG, Akbulut, O, Banister, CE et al.. Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer. Nat Commun. 2020;11 (1):2416. doi: 10.1038/s41467-020-16199-4. PubMed PMID:32415208 PubMed Central PMC7229173.
- Hornigold, N, Dunn, KR, Craven, RA, Zougman, A, Trainor, S, Shreeve, R et al.. Dysregulation at multiple points of the kynurenine pathway is a ubiquitous feature of renal cancer: implications for tumour immune evasion. Br J Cancer. 2020;123 (1):137-147. doi: 10.1038/s41416-020-0874-y. PubMed PMID:32390008 PubMed Central PMC7341846.
- ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium. Pan-cancer analysis of whole genomes. Nature. 2020;578 (7793):82-93. doi: 10.1038/s41586-020-1969-6. PubMed PMID:32025007 PubMed Central PMC7025898.
- Nikbakht, H, Jessa, S, Sukhai, MA, Arseneault, M, Zhang, T, Letourneau, L et al.. Latency and interval therapy affect the evolution in metastatic colorectal cancer. Sci Rep. 2020;10 (1):581. doi: 10.1038/s41598-020-57476-y. PubMed PMID:31953485 PubMed Central PMC6969060.
- Imai-Okazaki, A, Li, Y, Horpaopan, S, Riazalhosseini, Y, Garshasbi, M, Mosse, YP et al.. Heterozygosity mapping for human dominant trait variants. Hum Mutat. 2019;40 (7):996-1004. doi: 10.1002/humu.23765. PubMed PMID:31018026 PubMed Central PMC6617796.
- Bakadlag, R, Jandaghi, P, Hoheisel, JD, Riazalhosseini, Y. The potential of dopamine receptor D2 (DRD2) as a therapeutic target for tackling pancreatic cancer. Expert Opin Ther Targets. 2019;23 (5):365-367. doi: 10.1080/14728222.2019.1606904. PubMed PMID:30986128 .