Kirill V. Rosen

Education

• PhD, Moscow State University

Academic Positions

• Department member since 2002

Research Topics

Cancer, Cell Death, Cell Signalling

Research

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.

POSTDOCTORAL POSITIONS ARE AVAILABLE

Postdoctoral positions are available immediately for 2 years to identify novel targets for breast and colorectal cancer treatment. The laboratory works together with oncologists and pathologists at several cancer centres in Atlantic Canada, is well equipped for studies in cancer, molecular and cell biology and has access to state of the art genomic, proteomic, animal and imaging facilities.

Qualifications: Recent PhD with training documented by publications in international peer-reviewed journals. Background in cancer, molecular and cell biology is preferred.

Please send CV and contact information of three references to: Dr. Kirill Rosen, E-mail: kirill.rosen@dal.ca

RESEARCH ASSISTANT POSITION AVAILABLE

A position of a research assistant is available immediately for one year with an option to extend it further if mutually agreeable in a laboratory that studies molecular mechanisms of cancer (see Drucker A et al. Breast Cancer Res. 2020 22:105; Khan IA et al. Breast Cancer Res., 2018, 20:151; Yoo BH et al. Autophagy 2018, 14:134-151; Khan IA et al. Oncogene, 2016, 35:5759-5769 as well as Dr. Rosen's research interests at on this page). Research will be conducted within Atlantic Research Centre which is a division of Department of Pediatrics, Dalhousie University.

Qualifications: MSc degree in Biochemistry/Molecular Biology (or similar disciplines) and a demonstrated ability to work on a research project full time under supervision of the Principal Investigator.

Experimental skills: fluency in tissue culture, western blot, gene expression in mammalian cells and recombinant DNA techniques. Proficiency in cell proliferation and cell survival assays, fluorescence microscopy and mouse work is a definite asset. Salary is commensurate with qualifications and experience.

Please send CV and contact information of three references to: Dr. Kirill Rosen, E-mail: kirill.rosen@dal.ca

Keywords:

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

Current Lab Members

Publications

1. Chipurupalli, S., Jiang, P., Liu, X., Santos, J. L., Marcato, P., & Rosen, K. V. (2023). Three-dimensional growth sensitizes breast cancer cells to treatment with ferroptosis-promoting drugs. Cell Death Dis. 14(9):580. [PubMed] [Article]
2. Liu X, Chipurupalli S, Jiang P, Tavasoli M, Yoo BH, McPhee M, Mazinani S, Francia G, Kerbel RS, Rosen KV. (2022). ErbB2/Her2-dependent downregulation of a cell death-promoting protein BLNK in breast cancer cells is required for 3D breast tumor growth. Cell Death Dis. 13(8):687 [PubMed]
   
3. Surette A., Yoo BH., Younis T., Matheson K., Rameh, T., Snowdon, J., Bethune, G., and Rosen K.V. (2021) Tumor levels of the mediators of ErbB2-driven anoikis resistance correlate with breast cancer relapse after trastuzumab-based therapies. Breast Cancer Res. Treat. 2021 Mar 16. Online ahead of print. [Article] [PubMed]
   
4. Durcker A, Yoo BH, Khan IA, Choi D, Montermini L, Liu X, Jovanovic S, Younis T, Rosen KV., (2020) Trastuzumab-induced upregulation of a protein set in extracellular vesicles emitted by ErbB2-positive breast cancer cells correlates with their trastuzumab sensitivity. Breast Cancer Res. 22(1):105. [PubMed]
5. 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]
6. Khan IA, Yoo BH, McPhee M, Masson O, Surette A, Dakin-Hache K, Younis T, Bethune G, Rosen KV, (2018) ErbB2-driven downregulation of the transcription factor Irf6 in breast epithelial cells is required for their three-dimensional growth. Breast Cancer Research 20(1):151 [PubMed]
7. 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]
8. Klionsky D.J., ….Rosen K.V…et al. (multiple authors), (2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3d edition). Autophagy 12(1):1-222 [PubMed]
9. 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]
10. 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]
11. 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]
12. 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]
13. 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]
14. 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]
15. Klionsky DJ, ...Rosen KV,... (multiple authors), (2012) Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8:445-544 [PubMed]
16. 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]
17. 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]
18. 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]
19. 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]
20. 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]
21. 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]
22. 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]
23. 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]
24. 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]