Academic Rank:
Professor
Affiliation(s):
BC Cancer Research Centre
Location:
BC Cancer Research Centre

Short Bio:
  • Head, Clinical Diagnostic Genomics and Distinguished Scientist, Genome Sciences Centre, BC Cancer Agency
  • Medical Director, Cancer Genetics Lab, BC Cancer Agency
  • Hematopathologist, Pathology and Laboratory Medicine, BC Cancer Agency
  • Professor, Pathology and Laboratory Medicine, University of British Columbia (UBC)
  • Founding Member, Centre for Blood Research, University of British Columbia (UBC)
  • Member, Stem Cell Network

 

I make use of both, my clinical and research expertise in teaching. I teach Pathology and Internal Medicine residents and students clinical aspects of Hematology/Hematopathology. As well I give resident (Hematology/ Hematopathology, Oncology) seminars on tumor angiogenesis.

I teach graduate student courses using my expertise derived from my research interests in endothelial biology, apoptosis, angiogenesis and tumor biology, and stem cell differentiation. Currently much of my teaching time is spent on grad students, undergrads and high school students who are rotate through my laboratory.

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.

Academic Backgrounds:
  • BA, Magna Cum Laude, Queen’s University, Kingston, ON, Life Sciences
  • University of St. Andrews, Scotland, Exchange scholarship (Queen’s University)
  • MD, Queen’s University, Faculty of Medicine, Medicine
  • Fellow of the Royal College of Physicians and Surgeons of Canada – Hematological Pathology
Selected Publications
  • B.S. Sheffield MD, I.E. Bosdet PhD, R.H. Ali MD, S.S. Young PhD, B.K. McNeil BSc, C. Wong BSc, K. Dastur RT, A. Karsan MD, D.N. Ionescu MD. Relationship of TTF-1 to EGFR status in non-small cell lung cancer. Curr Oncol. 2014 Dec;21(6):305-8. doi: 10.3747/co.21.2148. PMID: 25489257.
  • Lai CK, Moon Y, Kuchenbauer F, Starzcynowski DT, Argiropoulos B, Yung E, Beer P, Schwarzer A, Sharma A, Park G, Leung M, Lin G, Vollett S, Fung S, Eaves CJ, Karsan A, Weng AP, Humphries RK, Heuser M. Cell fate decisions in malignant hematopoiesis: leukemia phenotype is determined by distinct functional domains of the MN1 oncogene. PLoS One. 2014 Nov 17;9(11):e112671. doi: 10.1371/journal.pone.0112671. eCollection 2014.
  • Wilson IM, Vucic EA, Enfield KSS, Thu KL, Zhang YA, Chari R, Lockwood WW, Radulovich N, Starczynowski DT, Banáth JP, Zhang M, Pusic A, Fuller M, Lonergan KM, Rowbotham D, Yee J, English JC, Buys TPH, Selamat SA, Laird-Offringa IA, Liu P, Anderson M, You M, Tsao MS, Brown CJ, Bennewith KL, MacAulay CE, Karsan A, Gazdar AF, Lam S, and Lam WL. EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk. Oncogene. 2014 Sep 4;33(36):
  • Cutz JC, Craddock KJ, Torlakovic E, Brandao G, Carter RF, Bigras G, Deschenes J, Izevbaye I, Xu Z, Greer W, Yatabe Y, Ionescu D, Karsan A, Jung S, Fraser RF, Blumenkrantz M, Lavoie J, Fortin F, Bojarski A, Cote GB, van den Berghe JA, Rashid-Kolvear F, Trotter M, Sekhon HS, Albadine R, Tran-Thanh D, Gorska I, Knoll JHM, Xu J, Blencowe B, Iafrate AJ, Hwang DM,Pintilie M, Gaspo R, Couture C, and Tsao MS . Canadian Anaplastic Lymphoma Kinase (ALK) study: A model for multi-centre standardization and Sep 2014
  • Gerrie A, Huang S.J,T, Bruyere H, Chinmay D, Hrynchak M, Karsan A, Ramadan K.M, Smith A.C, Tyson C, Toze C.L, Gillian T.L. Population-based characterization of the genetic landscape of chronic lymphocytic leukemia patients referred for cytogenetic testing in British Columbia, Canada: the role of provincial laboratory standardization. Cancer Genet. 2014 Jul-Aug;207(7-8):316-25. doi: 10.1016/j.cancergen.2014.08.006. Epub 2014 Aug 29. PMID: 25441686.
  • Patenaude A, Fuller M, Chang L, Wong F, Paliouras G, Shaw R, Kyle AH, Umlandt P, Baker JH, Diaz E, Tong J, Minchinton AI, Karsan A. Endothelial-specific Notch blockade inhibits vascular function and tumor growth through an eNOS-dependent mechanism. Cancer Res. 2014 May 1;74(9):2402-11. PMID:24599126.
  • Chang ACY, Garside VC, Fournier M, Smrz J, Vrljicak P, Umlandt P, Fuller M, Robertson G, Zhao Y, Tam A, Jones SJM,. Marra MA, Hoodless PA, Karsan A. A Notch-dependent transcriptional hierarchy promotes mesenchymal transdifferentiation in the cardiac cushion. Dev Dyn. 2014 Jul;243(7):894-905. doi: 10.1002/dvdy.24127. Epub 2014 Apr 17. PMID:24633789.
  • Mariano C, Bosdet I, Karsan A, Ionescu D, Murray N, Laskin JJ, Zhai Y, Melosky B, Sun S, Ho C. A population-based review of the feasibility of platinum-based combination chemotherapy after tyrosine kinase inhibition in EGFR mutation positive non-small cell lung cancer patients with advanced disease for consideration for publication in lung cancer. Lung Cancer. 2014 Jan;83(1):73-7. PMID:24192511.
  • Wilson IM, Vucic EA, Enfield KSS, Thu KL, Zhang YA, Chari R, Lockwood WW, Radulovich N, Starczynowski DT, Banáth JP, Zhang M, Pusic A, Fuller M, Lonergan KM, Rowbotham D, Yee J, English JC, Buys TPH, Selamat SA, Laird-Offringa IA, Liu P, Anderson M, You M, Tsao MS, Brown CJ, Bennewith KL, MacAulay CE, Karsan A, Gazdar AF, Lam S, and Lam WL. EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk. Oncogene. 2013 Oct 7. doi: 1
  • El-Sehemy A, Chang A, Azad AK, Gupta N, Xu Z, Steed H, Karsan A, Fu YX. Notch activation augments nitric oxide/soluble guanylyl cyclase signaling in immortalized ovarian surface epithelial cells and ovarian cancer cells. Cell Signal. 2013 Dec;25(12):2780-7.
Research:
  • Myelodysplastic syndromes and myeloid malignancies
  • Innate immune signaling in vascular and hematopoietic function
  • Genomics for clinical diagnostics
  •  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, Sash1, 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 results in perinatal death. Currently, we are generating a conditional gene-targeted mouse model to gain a better understanding of the physiologic role of Sash1.
  • 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.
  • Over the last few years my clinical interest has shifted to using genomics methodologies to deliver clinical diagnostic testing. We were the first clinical lab in Canada to use next-generation sequencing techniques to deliver clinical testing. We are currently developing various gene panels as well as genome-wide tests with the intention of taking these into the clinic.