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
akarsan@bccrc.ca
aly.karsan@ubc.ca
Lab Website: http://www.bcgsc.ca/faculty/dr-aly-karsan-md/

Current Positions

  • Medical Director, Cancer Genetics Laboratory, Pathology and Laboratory Medicine, BC Cancer Agency
  • Head, Clinical Diagnostic Genomics, Genome Sciences Centre, BC Cancer Agency
  • Professor, Pathology and Laboratory Medicine, UBC

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.

Publication

  1. Garside VC, Chang AC, Karsan A, Hoodless PA. Co-ordinating Notch, BMP, and TGF-β signaling during heart valve development. Cell Mol Life Sci. 2012 Nov 16.
  2. Venner CP, Wegrzyn Woltosz J, Nevill TJ, Deeg HJ, Caceres G, Platzbecker U, Scott BL, Sokol L, Sung S, List AF, Karsan A. Correlation of clinical response and response duration with miR-145 induction by lenalidomide in CD34+ cells from patients with del(5q) myelodysplastic syndrome. Haematologica. 2012 Aug 28.
  3. Vrljicak P, Cullum R, Xu E, Chang AC, Wederell ED, Bilenky M, Jones SJ, Marra MA, Karsan A, Hoodless PA. Twist1 transcriptional targets in the developing atrio-ventricular canal of the mouse. PLoS One. 2012;7(7):e40815.
  4. Chang L, Noseda M, Higginson M, Ly M, Patenaude A, Fuller M, Kyle AH, Minchinton AI, Puri MC, Dumont DJ, Karsan A. Differentiation of vascular smooth muscle cells from local precursors during embryonic and adult arteriogenesis requires Notch signaling. Proc Natl Acad Sci U S A. 2012 May 1;109(18):6993-8.
  5. Yip S, Butterfield YS, Morozova O, Chittaranjan S, Blough MD, An J, Birol I, Chesnelong C, Chiu R, Chuah E, Corbett R, Docking R, Firme M, Hirst M, Jackman S, Karsan A, Li H, Louis DN, Maslova A, Moore R, Moradian A, Mungall KL, Perizzolo M, Qian J, Roldan G, Smith EE, Tamura-Wells J, Thiessen N, Varhol R, Weiss S, Wu W, Young S, Zhao Y, Mungall AJ, Jones SJ, Morin GB, Chan JA, Cairncross JG, Marra MA. Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers. J Pathol. 2012 Jan;226(1):7-16. doi: 10.1002/path.2995. Epub 2011 Nov 10.
  6. Dauphinee SM, Voelcker V, Tebaykina Z, Wong F, Karsan A. Heterotrimeric Gi/Go proteins modulate endothelial TLR signaling independent of the MyD88-dependent pathway. Am J Physiol Heart Circ Physiol. 2011 Dec;301(6):H2246-53.
  7. Starczynowski DT, Lockwood WW, Deléhouzée S, Chari R, Wegrzyn J, Fuller M, Tsao MS, Lam S, Gazdar AF, Lam WL, Karsan A. TRAF6 is an amplified oncogene bridging the RAS and NF-κB pathways in human lung cancer. J Clin Invest. 2011 Oct;121(10):4095-105.
  8. Chang AC, Fu Y, Garside VC, Niessen K, Chang L, Fuller M, Setiadi A, Smrz J, Kyle A, Minchinton A, Marra M, Hoodless PA, Karsan A. Notch initiates the endothelial-to-mesenchymal transition in the atrioventricular canal through autocrine activation of soluble guanylyl cyclase. Dev Cell. 2011 Aug 16;21(2):288-300.
  9. Kuchenbauer F, Mah SM, Heuser M, McPherson A, Rüschmann J, Rouhi A, Berg T, Bullinger L, Argiropoulos B, Morin RD, Lai D, Starczynowski DT, Karsan A, Eaves CJ, Watahiki A, Wang Y, Aparicio SA, Ganser A, Krauter J, Döhner H, Döhner K, Marra MA, Camargo FD, Palmqvist L, Buske C, Humphries RK. Comprehensive analysis of mammalian miRNA* species and their role in myeloid cells. Blood. 2011 Sep 22;118(12):3350-8.
  10. Wegrzyn J, Lam JC, Karsan A. Mouse models of myelodysplastic syndromes. Leuk Res. 2011 Jul;35(7):853-62. Epub 2011 Apr 3.
  11. Fu Y, Chang AC, Fournier M, Chang L, Niessen K, Karsan A. RUNX3 maintains the mesenchymal phenotype after termination of the Notch signal. J Biol Chem. 2011 Apr 1;286(13):11803-13.
  12. Jädersten M, Karsan A. Clonal evolution in myelodysplastic syndromes with isolated del(5q): the importance of genetic monitoring. Haematologica. 2011 Feb;96(2):177-80.
  13. Starczynowski DT, Morin R, McPherson A, Lam J, Chari R, Wegrzyn J, Kuchenbauer F, Hirst M, Tohyama K, Humphries RK, Lam WL, Marra M, Karsan A. Genome-wide identification of human microRNAs located in leukemia-associated genomic alterations. Blood. 2011 Jan 13;117(2):595-607.
  14. Starczynowski DT, Kuchenbauer F, Wegrzyn J, Rouhi A, Petriv O, Hansen CL, Humphries RK, Karsan A. MicroRNA-146a disrupts hematopoietic differentiation and survival. Exp Hematol. 2011 Feb;39(2):167-178.e4.
  15. Starczynowski DT, Vercauteren S, Sung S, Brooks-Wilson A, Lam WL, Karsan A. Copy number alterations at polymorphic loci may be acquired somatically in patients with myelodysplastic syndromes. Leuk Res. 2011 Apr;35(4):444-7.
  16. Farinha P, Kyle AH, Minchinton AI, Connors JM, Karsan A, Gascoyne RD. Vascularization predicts overall survival and risk of transformation in follicular lymphoma. Haematologica. 2010 Dec;95(12):2157-60.
  17. Vercauteren SM, Sung S, Starczynowski DT, Lam WL, Bruyere H, Horsman DE, Tsang P, Leitch H, Karsan A. Array comparative genomic hybridization of peripheral blood granulocytes of patients with myelodysplastic syndrome detects karyotypic abnormalities. Am J Clin Pathol. 2010 Jul;134(1):119-26.
  18. Starczynowski DT, Karsan A. Innate immune signaling in the myelodysplastic syndromes. Hematol Oncol Clin North Am. 2010 Apr;24(2):343-59.
  19. Starczynowski DT, Karsan A. Deregulation of innate immune signaling in myelodysplastic syndromes is associated with deletion of chromosome arm 5q. Cell Cycle. 2010 Mar 1;9(5):855-6. Epub 2010 Mar 11.
  20. Murphy D, Parker J, Zhou M, Fadlelmola FM, Steidl C, Karsan A, Gascoyne RD, Chen H, Banerjee D. Constitutively overexpressed 21 kDa protein in Hodgkin lymphoma and aggressive non-Hodgkin lymphomas identified as cytochrome B5b (CYB5B). Mol Cancer. 2010 Jan 26;9:14.
  21. Patenaude A, Parker J, Karsan A. Involvement of endothelial progenitor cells in tumor vascularization. Microvasc Res. 2010 May;79(3):217-23.
  22. Vrljicak P, Chang AC, Morozova O, Wederell ED, Niessen K, Marra MA, Karsan A, Hoodless PA. Genomic analysis distinguishes phases of early development of the mouse atrio-ventricular canal. Physiol Genomics. 2010 Feb 4;40(3):150-7.

Education

  • Senior Research Fellow (Hematology), University of Washington, 1997
  • Residency, University of British Columbia, Canada, 1993
  • Intership, 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

Comments are closed, but trackbacks and pingbacks are open.