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Kirill V. Rosen

PhD (Moscow State University)


Professor (Biochemistry & Pediatrics)

Department member since 2002

CRC
902-494-7088
kirill.rosen@dal.ca

Research:

Cancer, Cell Death, Cell Signalling


Research Areas

Our studies are focused on the mechanisms by which oncoproteins Ras and beta-catenin promote colorectal cancer and those by which an oncoprotein ErbB2/Her2 drives breast cancer. Normal epithelial cells (from which these cancers originate) are attached in vivo to a specialized scaffold called the extracellular matrix (ECM). Detachment from the ECM kills the indicated cells. In contrast, cancer cells can survive without attachment to the ECM. This survival is thought to be critical for the ability of respective tumors to grow as three-dimensional masses, invade other tissues and metastasize to distant organs. We are working on identification of the mechanisms by which the indicated oncoproteins promote survival of cancer cells without adhesion to the ECM. In addition, we investigating how disruption of these mechanisms can be used for the design of novel cancer therapies. In case of the ErbB2/Her2-positive breast cancer we are also testing whether elements of the indicated mechanisms can serve as the biomarkers of breast cancer sensitivity to ErbB2-targeted therapies.

GRADUATE STUDENT POSITIONS ARE AVAILABLE

Graduate student (Master or Ph.D.) positions are available immediately to study the regulation of programmed cell death and autophagy in breast and colorectal cancer. Qualifications: The candidate should be academically acceptable to the Department of Biochemistry and Molecular Biology graduate program. This requires GPA 3.5 (or respective equivalent) or higher and significant research experience. Background in cancer research, molecular and cell biology is preferred. Please send CV, transcripts with grades (applications that do not contain transcripts with grades will not be considered) and contact information of three references to: Dr. Kirill Rosen, Atlantic Research Centre, Rm C-304, CRC, 5849 University Avenue, PO Box 15000, Halifax, NS B3H 4R2, Canada, FAX: 902-494-1394, E-mail: kirill.rosen@dal.ca.

Keywords:
Colorectal cancer, breast cancer, apoptosis, autophagy, biomarkers, RAS, beta-catenin, ErbB2/Her2

Postdoctoral Fellows

Byong Yoo The University of Texas at Dallas

Lab Personnel

Rob Douglas Research Assistant

Publications

  1. Yoo BH, Khan IA, Koomson A, Gowda P, Sasazuki T, Shirasawa S, Gujar S, Rosen KV, (2018) Oncogenic RAS-induced downregulation of ATG12 is required for survival of malignant intestinal epithelial cells. Autophagy 14(1):134-151 [PubMed]
  2. Khan IA, Yoo BH, Rak J and Rosen KV, (2017) Mek activity is required for ErbB2 expression in breast cancer cells growing in a three-dimensional manner. Oncotarget 8(62):105383-105396 [PubMed]
  3. Klionsky D.J., .Rosen K.Vet al. (multiple authors), (2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3d edition). Autophagy 12(1):1-222 [PubMed]
  4. Khan IA, Yoo BH, Masson O, Corkery D, Dellaire G, Baron S, Attardi LD and Rosen KV, (2016) ErbB2-dependent downregulation of a pro-apoptotic protein Perp is required for oncogenic transformation of breast epithelial cells. Oncogene 35:5759-57 [PubMed]
  5. Yoo BH, Masson O, Li Y, Khan I, Gowda P and Rosen KV, (2015) Anoikis of colon carcinoma cells triggered by β-catenin loss can be enhanced by Tumor Necrosis Factor Receptor 1 antagonists. Oncogene 34(38):4939-51 [PubMed]
  6. Yoo BH, Zagryazhskaya A, Li Y, Koomson A, Khan IA, Sasazuki T, Shirasawa S, and Rosen KV, (2015) Upregulation of ATG3 contributes to autophagy induced by the detachment of intestinal epithelial cells from the extracellular matrix, but promotes autophagy-independent apoptosis of the attached cells. Autophagy 11(8):1230-46 [PubMed]
  7. Arsenault DJ, Yoo BH, Rosen KV, Ridgway ND, (2013) ras-Induced up-regulation of CTP:phosphocholine cytidylyltransferase α contributes to malignant transformation of intestinal epithelial cells. J. Biol. Chem. 288:633-43 [PubMed]
  8. Junkins RD, Shen A, Rosen K, McCormick C, Lin TJ, (2013) Autophagy Enhances Bacterial Clearance during P. aeruginosa Lung Infection PLoS One 8(8): [PubMed]
  9. Yoo B, Berezkin A, Wang Y, Zagryazhskaya A and Rosen KV, (2012) Tumor suppressor protein kinase Chk2 is a mediator of anoikis of intestinal epithelial cells Int J Cancer 131:357-66 [PubMed]
  10. Klionsky DJ, ...Rosen KV,... (multiple authors), (2012) Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8:445-544 [PubMed]
  11. Yoo B.H., Wang Y, Erdogan M, Sasazuki S, Shirasawa S , Corcos L., Sabapathy K. and Rosen K.V. , (2011) Oncogenic ras-induced downregulation of a pro-apoptotic protease caspase-2 is required for malignant transformation of intestinal epithelial cells. J Biol Chem 286:38894-903 [PubMed]
  12. Yoo B.H., Wu X., Li Y., Haniff M., Sasazuki T., Shirasawa S., Eskelinen E.-L. and Rosen K.V., (2010) Oncogenic ras-induced downregulation of autophagy mediator Beclin-1 is required for malignant transformation of intestinal epithelial cells. J. Biol. Chem. 285:5438-49 [PubMed]
  13. Li H., Ray G., Yoo B.H., Erdogan M. and Rosen K.V. , (2009) Downregulation of DAP kinase-2 is required for beta-catenin-induced anoikis resistance of malignant epithelial cells. J. Biol. Chem. 284:2012-2022 [PubMed]
  14. Yoo B.H., Wu X., Derouet M., Haniff M., Eskelinen E.-L. and Rosen K.V., (2009) Hypoxia-induced downregulation of autophagy mediator Beclin-1 reduces the susceptibility of malignant intestinal epithelial cells to hypoxia-dependent apoptosis. Autophagy 5:1166-79 [PubMed]
  15. Derouet M., Wu X., May L., Yoo BH, Sasazuki T., Shirasawa S., Rak J. and Rosen KV, (2007) Acquisition of anoikis resistance promotes the emergence of oncogenic K-ras mutations in colorectal cancer cells and stimulates their tumorigenicity in vivo. Neoplasia 9(7):536-545 [PubMed]
  16. Liu, Z., Li, H., Derouet, M., Berezkin, A., Sasazuki, T., Shirasawa, S., and Rosen, K. , (2006) Oncogenic Ras inhibits anoikis of intestinal epithelial cells by preventing the release of a mitochondrial pro-apoptotic protein Omi/HtrA2 into the cytoplasm. J. Biol. Chem. 281:14738-47 [PubMed]
  17. Liu, Z., Li, H., Wu, X., Yoo, B., Yan, S., Stadnyk, A., Sasazuki, T., Shirasawa, S., LaCasse, E., Korneluk, RG. and Rosen KV, (2006) Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal epithelial cells. Oncogene 25:7680-90 [PubMed]
  18. Liu Z, Li H, Derouet M, Filmus J, LaCasse EC, Korneluk RG, Kerbel RS, and Rosen KV , (2005) ras oncogene triggers upregulation of cIAP2 and XIAP in intestinal epithelial cells: EGF receptor-dependent and -independent mechanisms of ras-induced transformation. J. Biol. Chem. 280:37383-37392 [PubMed]
  19. Yan SR, Joseph RR, Rosen K, Reginato MJ, Jackson A, Allaire N, Brugge JS, Jobin C, Stadnyk AW, (2005) Activation of NF-kappaB following detachment delays apoptosis in intestinal epithelial cells. Oncogene 24:6482-91 [PubMed]