Aly Karsan

Contact Information
British Columbia Cancer Research Centre
Rm 9-111, 675 West 10th Ave, Vancouver, British Columbia, Canada V5Z1L3
Tel: 1-604-675-8033
Fax: 1-604-675-8049
Email: akarsan@bccrc.ca
Email: aly.karsan@ubc.ca
Email:  akarsan@bcgsc.ca
Lab Website: http://www.bcgsc.ca/faculty/dr-aly-karsan-md/

Current Positions

  • Head, Clinical Diagnostic Genomics, Genome Sciences Centre, BC Cancer Agency.
  • Medical Director, Centre for Clinical Genomics, Michael Smith Genome Sciences Centre, BC Cancer Agency.
  • Medical Director, Cancer Genetics Laboratory, Pathology and Laboratory Medicine, BC Cancer Agency.
  • Professor, Pathology and Laboratory Medicine, University of British Columbia.
  • Member, Experimental Medicine, University of British Columbia.
  • Founding Member, Centre for Blood Research, University of British Columbia.
  • Member, Stem Cell Network.

Research Interests

  • Myelodysplastic syndromes.
  • Innate immune signaling in vascular and hematopoietic function.
  • Role of Notch in cardiovascular development and angiogenesis.

My lab focuses on two major areas:
(1) Understanding the molecular basis of the preleukemic bone marrow failure conditions called myelodysplastic syndromes (MDS); and
(2) Determining the role of the endothelium in the development of the hematopoietic system. With respect to both areas we have been studying the role of two pathways: innate immune signaling as represented by the Toll-like receptor (TLR) pathways, and the Notch signaling pathway.

We have recently demonstrated that microRNAs that reside on the long arm of chromosome 5 act to regulate innate immune signaling. Deletion of chromosome arm 5q is the commonest structural anomaly seen in MDS, and our current work is centred around establishing the function of these microRNAs and deregulated innate immune signaling in the manifestations of MDS. We are using a variety of in vivo transplantation assays, in vitro cell biology and cell signaling studies as well as genomic approaches to answer these questions.

In other work related to innate immune signaling, we have identified a novel protein by differential proteomic analysis that appears to act as a scaffold protein in a MyD88-independent TLR signal transduction pathway. Expression analyses indicate that this molecule is highly expressed in the microvasculature. Molecular and cellular studies to elucidate the mechanisms of action of this protein are ongoing. As well we have generated a gene-targeted mouse model that demonstrates that loss of this protein is incompatible with life past mid-gestation. Currently, we are generating a conditional gene-targeted mouse model to gain a better understanding of the physiologic role of this protein.

My lab has also had a long-standing interest in the role of Notch signaling in the endothelium. We have generated a conditional, inducible mouse model in which we are able to regulate Notch signaling. Using this and other models we are studying how endothelial cells contribute to hematopoietic development both at the initial stages of intraembryonic hematopoiesis where hematopoietic stem cells are thought to derive from the endothelium, as well as during fetal liver and adult hematopoiesis, where the endothelium may act as a niche to regulate stem cell self renewal and/or differentiation.

Key Papers

  1. Lam J, Van Den Bosch M, Wegrzyn-Woltosz J, Parker J, Ibrahim R, Slowski K, Chang L,Martinez-Hoyer S, Umlandt P, Fuller M, Karsan A. Loss of miR-143 and miR-145 inhibithematopoietic stem cell activity but enhance progenitor activity through activation of TGFβ signaling. Nature Communications volume 9, Article number: 2418 (2018).
  2. Agrahari R, Foroushani A, Docking TR, Chang L, Duns G, Hudoba M, Karsan A*, Zare H*. Applications of Bayesian network models in predicting types of hematological malignancies. *co-senior authors. Sci Rep. 2018 May 3;8(1):6951. doi: 10.1038/s41598-018-24758-5. PMID: 29725024.

Selected Publications

  1. Alcaide M, Cheung M, Bushell K, Arthur SE, Wong HL, Karasinska J, Renouf D, Schaeffer DF, McNamara S, Tertre MCD, Batist G, Kennecke HF, Karsan A, Morin RD.A Novel Multiplex Droplet Digital PCR Assay to Identify and Quantify KRAS Mutations in Clinical Specimens. J Mol Diagn. 2018 Nov 23. pii: S1525-1578(18)30114-4. doi: 10.
  2. Haase D, Stevenson KE, Neuberg D, Maciejewski JP, Nazha A, Sekeres MA, Ebert BL, Garcia-Manero G, Haferlach C, Haferlach T, Kern W, Ogawa S, Nagata Y, Yoshida K, Graubert TA, Walter MJ, List AF, Komrokji RS, Padron E, Sallman D, Papaemmanuil E, Campbell PJ, Savona MR, Seegmiller A, Adès L, Fenaux P, Shih LY, Bowen D, Groves MJ, Tauro S, Fontenay M, Kosmider O, Bar-Natan M, Steensma D, Stone R, Heuser M, Thol F, Cazzola M, Malcovati L, Karsan A, Ganster C, Hellström-Lindberg E, Boultwood J, Pellagatti A, Santini V, Quek L, Vyas P, Tüchler H, Greenberg PL, Bejar R; International Working Group for MDS Molecular Prognostic Committee. TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups.Leukemia. 2019 Jan 11. doi: 10.1038/s41375-018-0351-2.
  3. Hui T, O’Neil K, Wegrzyn-Woltosz J, Laks E, Mingay M, Moksa M, Aparicio S, Karsan A, Hirst M. High-Resolution Single-Cell DNA Methylation Measurements Reveal Epigenetically Distinct Hematopoietic Stem Cell Subpopulations. Stem Cell Reports. 2018 Jul 27. pii: S2213-6711(18)30308-4. doi: 10.1016/j.stemcr.2018.07.003. 11: 578-592. PMID: 30078558.
  4. Blais J, Giroux S, Caron A, Clément V, Dionne-Laporte A, Jouan L, Gauthier J, MacLeod T, Moore R, Parker J, Swanson L, Zhao Y, Rouleau G, Karsan A, Langlois S, Rousseau F. Non-invasive prenatal aneuploidy testing: Critical diagnostic performance parameters predict sample z-score values. Clin Biochem. 2018 Jun 26. pii: S0009-9120(18)30491-0. doi: 10.1016/j.clinbiochem.2018.06.015. 59: 69-77.. PMID: 29958880.
  5. Lam J, Van Den Bosch M, Wegrzyn-Woltosz J, Parker J, Ibrahim R, Slowski K, Chang L,Martinez-Hoyer S, Umlandt P, Fuller M, Karsan A. Loss of miR-143 and miR-145 inhibit hematopoietic stem cell activity but enhance progenitor activity through activation of TGFβ signaling. Nature Communications volume 9, Article number: 2418 (2018).
  6. Bidshahri R, Fakhfakh K, McNeil K, Karsan A, Won JR, Wolber R, Hughesman C, Haynes C. Quantitative analysis of KRAS G12/G13 status in colorectal cancer using a novel wild-type negative assay that unequivocally differentiates missense and synonymous alleles. J Mol Diagn. Accepted.
  7. Agrahari R, Foroushani A, Docking TR, Chang L, Duns G, Hudoba M, Karsan A*, Zare H*. Applications of Bayesian network models in predicting types of hematological malignancies. *co-senior authors. Sci Rep. 2018 May 3;8(1):6951. doi: 10.1038/s41598-018-24758-5. PMID: 29725024.
  8. Stockley T,  Souza C, Cheema P, Melosky B,  Kamel-Reid S, Tsao M,  Spatz A, Karsan A. Evidence-Based Best Practices for EGFR-T790M Testing in Lung Cancer in Canada.. Curr Oncol. 2018 Apr; 25(2): 163–169. Published online 2018 Apr 30. doi:  10.3747/co.25.4044 PMID: 29719432.
  9. Cremin C, Howard S, Le L, Karsan A, Schaeffer DF, Renouf D, Schrader KA. CDKN2A founder mutation in pancreatic ductal adenocarcinoma patients without cutaneous features of Familial Atypical Multiple Mole Melanoma (FAMMM) syndrome. Hered Cancer Clin Pract. 2018 Mar 7;16:7. doi: 10.1186/s13053-018-0088-y. eCollection 2018. PMID:29541281.
  10. Liu K, Lu XJ, Cheng Y, Klieb H, Ng S, McNeil K, Karsan A, Poh C. An actionable test using loss of heterozygosity in identifying high-risk oral premalignant lesions. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Dec 18. pii: S2212-4403(17)31208-7. doi: 10.1016/j.oooo.2017.10.019. PMID: 29428696.
  11. Zhao EY, Shen Y, Pleasance E, Kasaian K, Leelakumari S, Jones M, Bose P, Ch’ng C, Reisle C, Eirew P, Corbett R, Mungall KL, Thiessen N, Ma Y, Schein JE, Mungall AJ, Zhao Y, Moore RA, Den Brok W, Wilson S, Villa D, Shenkier T, Lohrisch C, Chia S, Yip S, Gelmon K, Lim H, Renouf D, Sun S, Schrader KA, Young S, Bosdet I, Karsan A, Laskin J, Marra MA, Jones SJM. Homologous Recombination Deficiency and Platinum-Based Therapy Outcomes in Advanced Breast Cancer. Clin Cancer Res. 2017 Dec 15;23(24):7521-7530. doi: 10.1158/1078-0432.CCR-17-1941. PMID 29246904.
  12. Enfield K,  Marshall E,  Ng K, Anderson C,  Rahmati S, Lam S,  Macaulay C,  Lockwood W, Karsan A,  Jurisica I,  Lam W. Inhibition of the Novel Oncogene ELF3 Abolishes Lung Adenocarcinoma Growth. Journal of Thoracic Oncology. November 2017 Volume 12, Issue 11, Supplement 2, Page S1763 DOI: http://dx.doi.org/10.1016/j.jtho.2017.09.366.
  13. Tsao M, Zhang T, Cheema P, Laskin J, Karsan A, Barnes T, Liu G, Owen S, Rothenstein J, Burkes R,  Iqbal M, Spatz A, Izevbaye I, Kempen L, Kamel-Reid S, Leighl N. Canadian Multicenter Validation Study of Plasma Circulating Tumor DNA for Epidermal Growth Factor (EGFR) T790M Testing. Journal of Thoracic Oncology, November 2017, Volume 12, Issue 11, Supplement 2, Page S2207 DOI: http://dx.doi.org/10.1016/j.jtho.2017.09.1460.
  14. Grewal JK, Eirew P, Jones M, Chiu K, Tessier-Cloutier B, Karnezis AN, Karsan A, Mungall A, Zhou C, Yip S, Tinker AV, Laskin J, Marra M, Jones SJM. Detection and Genomic Characterization of a mammary-like adenocarcinoma. Cold Spring Harb Mol Case Stud. 2017 Nov 21;3(6). pii: a002170. doi: 10.1101/mcs.a002170. PMID: 28877932.
  15. Lai CK, Norddahl GL, Maetzig T, Rosten P, Lohr T, Sanchez Milde L, von Krosigk N, Docking TR, Heuser M, Karsan A, Humphries RK. Meis2 as a critical player in MN1-induced leukemia. Blood Cancer J. 2017 Sep 29;7(9):e613. doi: 10.1038/bcj.2017.86. PMID: 28960191.
  16. Yi Y, Tsai SH, Cheng JC, Wang EY, Anglesio MS, Cochrane DR, Fuller M, Gibb EA, Wei W, Huntsman DG, Karsan A, Hoodless PA. APELA promotes tumour growth and cell migration in ovarian cancer in a p53-dependent manner. Gynecol Oncol. 2017 Dec;147(3):663-671. doi: 10.1016/j.ygyno.2017.10.016. December 2017. PMID: 29079036.
  17. Wong HL, Yang KC, Shen Y, Zhao EY, Loree JM, Kennecke HF, Kalloger SE, Karasinska JM, Lim HJ, Mungall AJ, Feng X, Davies JM, Schrader K, Zhou C, Karsan A, Jones SJ, Laskin J, Marra MA, Schaeffer DF, Gorski SM, Renouf DJ. Molecular characterisation of metastatic pancreatic neuroendocrine tumours (PNETs) using whole genome and transcriptome sequencing. Cold Spring Harb Mol Case Stud. 2017 Nov 1. pii: mcs.a002329. doi: 10.1101/mcs.a002329. PMID:29092957.
  18. Chang KTE, Goytain A, Tucker T, Karsan A, Lee CH, Nielsen TO, Ng TL. Development and Evaluation of a Pan-Sarcoma Fusion Gene Detection Assay Using the NanoString nCounter Platform. J Mol Diagn. 2017 Nov 17. pii: S1525-1578(17)30314-8. doi:10.1016/j.jmoldx.2017.09.007. PMID: 29104083.
  19. Hout DR, Schweitzer BL, Lawrence K, Morris SW, Tucker T, Mazzola R, Skelton R, McMahon F, Handshoe J, Lesperance M, Karsan A, Saltman DL.Performance of a RT-PCR Assay in Comparison to FISH and Immunohistochemistry for the Detection of ALK in Non-Small Cell Lung Cancer. Cancers (Basel). 2017 Aug 1;9(8). pii: E99. doi: 10.3390/cancers9080099 PMID: 28763012.
  20. Lebo MS, Zakoor KR, Chun K, Speevak MD, Waye JS, McCready E, Parboosingh JS, Lamont  RE, Feilotter H, Bosdet I, Tucker T, Young S, Karsan A, Charames GS, Agatep R, Spriggs EL, Chisholm C, Vasli N, Daoud H, Jarinova O, Tomaszewski R, Hume S, Taylor S, Akbari MR, Lerner-Ellis J; Canadian Open Genetics Repository Working Group. Data sharing as a national quality improvement program: reporting on BRCA1 and BRCA2 variant-interpretation comparisons through the Canadian Open Genetics Repository (COGR). Genet Med. 2017 Jul 20. doi: 10.1038/gim.2017.80. PMID:28726806.
  21. Cabanero M, Sangha R, Sheffield BS, Sukhai M, Pakkal M, Kamel-Reid S, Karsan A, Ionescu D, Juergens RA, Butts C, and Tsao MS. Management of EGFR Mutated NSCLC: Practical Implications from a Clinical and Pathology Perspective. Curr Oncol. 2017 Apr;24(2):111-119. doi: 10.3747/co.24.3524. PMID: 28490925.
  22. Weymann D, Laskin J, Roscoe R, Schrader I, Chia S, Yip S, Cheung W, Gelmon K, Karsan A, Renouf D, Marra M, Regier D. The cost and cost-trajectory of whole-genome analysis guiding treatment of  patients with advanced cancers. Clin Genet. 2017 Mar 12;5(3):251-260. doi: 10.1002/mgg3.281. PMID: 28546995.
  23. Thibodeau ML, Reisle C, Zhao E, Martin LA, Alwelaie Y, Mungall KL, Ch’ng C, Thomas R, Ng T, Yip S, J Lim H, Sun S, Young SS, Karsan A, Zhao Y, Mungall AJ, Moore RA, J Renouf D, Gelmon K, Ma YP, Hayes M, Laskin J, Marra MA, Schrader KA, Jones SJM. Genomic profiling of pelvic genital type leiomyosarcoma in a woman with a germline CHEK2:c.1100delC mutation and a concomitant diagnosis of metastatic invasive ductal breast carcinoma. Cold Spring Harb Mol Case Stud. 2017 Sep 1;3(5). pii: a001628. doi: 10.1101/mcs.a001628. Print 2017 Sep. PMID: 28514723.
  24. Goy J, Gillan T, Huang S, Karsan A, Ramadan K, Bruyere H, Toze C, Gerrie A, Hrynchak M and Connors J. Chronic lymphocytic leukemia patients with deletion 11q have a short time to requirement of first-line therapy, but long overall survival: results of a population-based cohort in British Columbia, Canada. Clin Lymphoma Myeloma Leuk. 2017 Jun;17(6):382-389. pii: S2152-2650(17)30205-7. doi: 10.1016/j.clml.2017.04.001. PMID: 28559149.
  25. O’Neill K, Hills M, Gottlieb M, Karsan A and Lansdorp P. Assembling Draft Genomes using contiBAIT. Bioinformatics. 2017 Sep 1;33(17):2737-2739. doi: 10.1093/bioinformatics/btx281.PMID: 28475666.
  26. Foroushani A, Agrahari R, Docking R, Chang L, Duns G, Hudoba M, Karsan A*, Zare H* (co-senior authors). Large-scale gene network analysis reveals the significance of extracellular matrix pathway and homeobox genes in acute myeloid leukemia: an introduction to the Pigen gene package and its applications. BMC Med Genomics. 2017 Mar 16;10(1):16. PMID: 28298217.
  27. Huang SJ, Lee LJ, Gerrie AS, Gillan TL, Bruyere H, Hrynchak M, Smith AC, Karsan A, Ramadan KM, Jayasundara KS, and Toze CL. Characterization of treatment and outcomes in a population-based cohort of patients with chronic lymphocytic leukemia referred for cytogenetic testing in British Columbia, Canada. Leuk Res. 2017 Jan 15;55:79-90. PMID: 28157628.
  28. Huang S, Gerrie A, Bergin K, Gillan T, Bruyere H, Smoth A, Ramadan K, Karsan A, Dalal C, Toze C, Azue K. Clonal evolution as detected by interphase fluorescence in situ hybridization is associated with worse Overall survival in a population-based analysis of patients with chronic lymphocytic leukemia in British Columbia, Canada. Cancer Genet. 2017 Jan: 210:1-8. http://dx.doi.org/10.1016/j.cancergen.2016.10.006. PMID: 28212806.
  29. Young S, Tucker T, Bosdet I, Karsan A. Estimating deep molecular responses in chronic myelogenous leukemia: a Bayesian approach. Leukemia. 2016 Jul;30(7):1628-9. PMID: 26952806.
  30. Parker J, Shen Y, Pleasance E,  Li Y, Schein J, Zhao Y, Moore R, Wegrzyn-Woltosz J, Savage K, Weng A, Gascoyne R, Jones S, Marra M, Laskin J, Karsan A. Molecular etiology of an indolent lymphoproliferative disorder determined by whole-genome sequencing. Cold Spring Harb Mol Case Stud. 2016 March 2. Stud  2: a000679. PMID: 27148583.

Education

  • Senior Research Fellow (Hematology), University of Washington, 1997.
  • Residency, University of British Columbia, Canada, 1993.
  • Internship, Lions Gate Hospital, Canada, 1987.
  • M.D., Queen’s University at Kingston, Canada, 1986.
  • B.A. (Life Science), Queen’s University at Kingston, Canada, 1983.