Stephen Lee, Ph.D.
Ph.D.: McGill University, Montreal, Quebec - 1994
RGN, 451 Smyth Road, Rm. 3157, Ottawa ON K1H 8M5
IN THE NEWS
7/05/2012: Congratulation to Dr. James Uniacke and the team for our recent paper in Nature
An Oxygen-Regulated Switch in the Protein Synthesis Machinery
15/01/2012: Congratulation to Dr. Timothy Audas and the team for our recent paper in Molecular Cell
RNA Imprison Proteins in the Nucleolus
Our laboratory provides a vibrant bilingual environment for highly motivated students and post-doctoral Fellows. Members of my laboratory are part of a multi-discipline team trained in protein biochemistry, cell biology and molecular biology techniques to answer fundamental questions in modern biology. Successful trainees regularly publish in premier scientific journals, present their work at international forums and receive local as well as National honors and awards. The laboratory is very-well funded and equipped providing an excellent setting for creativity and productivity.
Les étudiants francophones qui sont à la recherche d’un environnement scientifique bilingue sont les bienvenus dans mon laboratoire
Laboratory Mantra: Fermentation is life without oxygen (Louis Pasteur 1861)
Statement of our Research "Science without oxygen": Louis Pasteur discovered fermentation in the 19th century and suggested that cells can live without oxygen. This is important since it suggests that our cells are equipped with an evolutionary program that enables an adaptive “switch” from an aerobic to anaerobic environment. Most of the scientific work of the 20th century has focused on our understanding of basic and specialized cellular mechanisms in the presence of oxygen. The question that we are asking is "how do cells adjust to low oxygen availability and how do they switch-on this adaptive program?"
This research has a far-reaching range of applications in the study of adaptation to high altitude, muscle exercise, development and disease. For example, a “switch-on” would facilitate subsistence of cells during an ischemic episode and a “switch-off” would prevent cancer cells from surviving in the core of a tumour.
Our laboratory has uncovered surprising and unforeseen cellular processes while studying cellular adaptation to anaerobic metabolism. Below are the two major Research Themes of the laboratory.
Theme 1: RNA imprisons proteins: a novel mechanism of post-translational regulation
We have discovered that anaerobic metabolism induces a novel class of non-coding RNA transcribed from the intergenic spacer (previously known as “untranscribed (!) spacer) of the nucleolus. The function of these non-coding RNAs is to immobilize and inactivate a large subset of proteins that cells we may not need during periods of reduced oxygen availability.
A recent paper from the laboratory on Theme 1.
Theme 2: Protein synthesis without oxygen: an unexpected way that cells use to synthesize protein in low oxygen tension.
We learn early on during our studies how cells produce proteins (i.e. protein synthesis). Oddly, the basic protein synthesis machinery is inoperative in low oxygen tension. So how do our cells make proteins during anaerobic metabolism? Our laboratory has just uncovered a remarkably interesting, and very unexpected, mechanism of translation initiation
A recent paper from the laboratory on Theme 2.
- See AACR Editorial (2012) "HIF-2a mediates hypoxia-inducible translation"
Our laboratory has been successful in securing several University and National Awards. Below is a chronological list of some of these Awards
2011- Dr. James Uniacke; Recipient of the 1st Prize for Best Poster, RiboClub Sherbrooke Quebec.
2010- Dr. James Uniacke; Recipient of a Post-Doctoral Scholarship from the National Cancer Institute of Canada.
2009- Dr. Aleksandra Franovic; Recipient of the Harold E. Johns Award from the Canadian Cancer Society for 1st Place in the National Doctoral Award Competition.
2008- Dr. Karim Mekhail; Recipient of NSERC Best Ph.D. Thesis of the Year in Canada Award
2007- Dr. Karim Mekhail; Recipient of the Governor General Gold Medal Award for Best Ph.D. Thesis at the University of Ottawa in the Natural Sciences.
2007- Ms. Aleksandra Franovic; Recipient of the Excellence in Research Award of the Faculty of Medicine of the University of Ottawa.
2007- Dr. Karim Mekhail; Represented the University of Ottawa for the National CAGS/UMI Distinguished Dissertation Award
2007- Mr. Luis Rivero; Nominated for Best M.Sc. Thesis at the University of Ottawa.
2005- Ms. Aleksandra Franovic; Recipient of the Best Poster Award in CMM .
2005- Dr. Karim Mekhail; Recipient of the Canada Award from NSERC.
2003- Ms. Natalie de Paulson; Recipient of the Best M.Sc. Thesis at the University of Ottawa.
2001- Ms. Marie-Eve Bonicalzi; Recipient of the Best M.Sc. Thesis at the University of Ottawa.
Stephen Lee, Ph.D.
- Published papers from his group in Mol. Cell, Nature and Nature Cell Biol.
- Funded by multiple grants from CIHR
- Recipient of the Harold E. Johns Award from the National Cancer Institute of Canada
- Joined the Department of Cellular and Molecular Medicine in 1998.
- Trained as a post-doctoral fellow in the laboratory of Dr. Richard Klausner at the National Cancer Institute, Bethesda MD.
- Received his Ph.D. from McGill University in 1994.
Josianne Payette - Laboratory Manager
- Established a productive, responsible and convivial training environment
- Published published several high profile manuscripts
- Attended multiple international scientific conference
- Graduated with a College Degree in Biotechnology from La Cite Collégiale in 2004
- Joined the Laboratory in 2004
Dr. Timothy Audas - Post Doctoral Fellow
2007: Ph.D Molecular and Cellular Biology, University of Guelph
2005: NSERC Postgraduate Student Scholarship
2002: B.Sc. (Hons) Molecular Biology and Genetics, University of Guelph
Dr. James Uniacke - Post Doctoral Fellow
- 2011: Best talk prize, fourth place. International Hypoxia Symposia. Lake Louise, Alberta
- 2010: Best poster prize, first place. Riboclub annual meeting. Mount-Orford, Qc
- 2009: The Terry Fox Foundation Postdoctoral Fellowship. Canadian Cancer Society, 3 years
- 2009: Ph.D. Biology, Concordia University. Supervisor: Dr. William Zerges
- 2009: Represented Concordia University as the NSERC Doctoral Prize nominee
- 2008: Best paper of the year. The Canadian Society of Plant Physiologists.
- 2008: Best seminar of the year. Riboclub monthly RNA meetings. University of Sherbrooke, Sherbrooke, Qc.
Dr. Taylor Mullineux - Post Doctoral Fellow
- 2011: Post-doctoral fellow at Université Libre de Bruxelles, Belgium.Supervisor: Dr. Denis Lafontaine
- 2010: Ph.D. Microbiology, University of Manitoba. Supervisor: Dr. Georg Hausner
- 2009: Manitoba Health Research Council Award
- 2006: University of Manitoba Graduate Fellowship
- 2005: Howard Lees Scholarship in Microbiology
- 2004: NSERC Postgraduate Scholarship M
- 2004: B.Sc. with distinction, University of Manitoba
Camille Francisco - Graduate Student
- 2010: Recipient of Ontario Graduate Scholarship
- 2009-2011: University of Ottawa Excellence Scholarship
- 2009: Graduated from Carleton University: Bachelor of Science Honours Major in Integrated Science: Concentration in Forensic
- Science and a Minor Psychology (Summa Cum Laude)
Gabriel Lachance - Graduate Student
- Present: Ph.D. in Cellular and Molecular Medicine, University of Ottawa.
- 2008: M.Sc. in Cellular and Molecular Biology, Sherbrooke University.
- 2005:B.Sc in Biochemistry, Université Laval
Mathieu Jacob - Graduate Student
- 2009: Present: PhD Cellular and Molecular Medicine, University of Ottawa
- 2008: Hon.B.Sc. in Genetics and Biotechnology, University of Toronto
- 2008: Manufacturing Technology intern, Sanofi Pasteur Ltd
- 2007-2008: Honours Student, Dept. of Molecular Genetics
- 2007: Research Assistant, Dept. of Chemistry
Tahmina Omar - Graduate Student
- 2009: Canadian Institute of Health Research Studentship Scholarship
- 2009: Bachelor of Science, Honours in Biopharmaceutical Sciences from the University of Ottawa.
Joseph Kishan Perera - Graduate Student
- 2011: Bsc. Honours in Biomedical Science (Summa Cum Laude)
- 2011: Ontario Graduate Scholarship
- 2011: University of Ottawa Excellence Scholarship
- 2010: endMS Studentship
- 2007-2011: University of Ottawa Admission Scholarship
- 2007-2011: Dean's Honour list
Dr. Aleksandra Franovic
- Published several high profile scientific manuscript as first author
- 2010: Post-doctoral Fellow, UCSD
- 2009: Ph.D. in Cellular and Molecular Medicine, University of Ottawa
- 2009: Recipient of the Harold E. Johns Award from the Canadian Cancer Society for 1st Place in the National Doctoral Award Competition.
- 2007: Research Excellence Award, Faculty of Medicine
- 2005: University of Ottawa Excellence Scholarship
- 2005: NSERC Postgraduate Student Scholarship
- 2004: B.Sc. Honors Biochemistry (Summa Cum Laude)
- 2004: B.A.Sc. Chemical Engineering, Biotechnology (Magna Cum Laude)
Mireille Khacho, Ph.D. Student
- Published several high profile scientific manuscript as first author2000: Honors Biochemistry, University of Ottawa
- 2010: Post-doctoral Fellow, University of Ottawa
- 2008: Ph.D. in Cellular and Molecular Medicine, University of Ottawa.
- 2003: M. Sc. in Cellular and Molecular Medicine, University of Ottawa.
Dr. Lakshman Gunaratnam, M.D., M.Sc.
- 2009: Assistant Professor, Western University
- 2007: Instructor, Harvard Medical School
- 2005: Canadian Institutes of Health Research Fellowship
- 2005: Royal college of Physicians and Surgeons of Canada-Canadian Research Award for Specialty Residents (Single National Award)
- 2005: Fellowship in Nephrology, Harvard Medical School/Brigham and Women’s Hospital-Massachusetts General Hospital Joint Program
- 2002: Doctorate in Medicine, University of Ottawa
- Selected Publications:
Franovic A, Gunaratnam L(equal first authorhip), Smith K, Robert I, Patten D, and Lee S. (2007) Translational up-regulation of the EGFR by tumor hypoxia provides a nonmutational explanation for its overexpression in human cancer. Proc Natl Acad Sci. 104:13092-13097.
Mekhail K, Gunaratnam L, Bonicalzi ME, Lee S. (2004) HIF activation by pH-dependent nucleolar sequestration of VHL. Nature Cell Biol. 6:642-647.
Gunaratnam L, Morley M, Franovic A, De Paulsen N, Mekhail K, Parolin DA, Nakamura E, Lorimer IA, and Lee S. (2003) HIF activates the TGF-alpha /EGF-R growth stimulatory pathway in VHL-/- renal cell carcinoma cells. J Biol Chem. 278:44966-44974.
Dr. Karim Mekhail, Ph.D.
- 2009: Assistant Professor, University of Toronto
- 2008: NSERC, Best Ph.D. Thesis in Canada
- 2007: Canadian Governor General’s Gold Medal in the Sciences (2007)
- 2006: Post-doctoral Fellow, Harvard University
- 2006: CIHR Post-doctoral Fellowship
- 2005: NSERC Canada Graduate Scholarship-Doctoral
- 2006: Ph.D. in Cellular and Molecular Medicine, University of Ottawa.
- Selected Publications:
Mekhail , K., Gunaratnam, L., Bonicalzi, M. E., and Lee, S. (2004) HIF activation by pH-dependent nucleolar sequestration of VHL. Nature Cell Biol.6:642-647.
Mekhail , K., Khacho, M., Carrigan, A., Hache, R. J., Gunaratnam, L., and Lee, S. (2005) Regulation of ubiquitin ligase dynamics by the nucleolus. J. Cell Biol. 170:733-744.
Mekhail , K., Rivero-Lopez, L., Al-Masri, A., Brandon, C., Khacho, M., and Lee, S. (2007) Identification of a common subnuclear localization signal. Mol. Biol. Cell 18:3966-3977.
- Uniacke, J., Holterman, C. E., Lachance, G., Franovic, A., Jacob, M. D., Fabian, M. R., Payette, J., Holcik, M., Pause, A., and Lee, S. (2012) An Oxygen-Regulated Switch in the Protein Synthesis Machinery. Nature 486:126
- Audas, T., Jacob, M., and Lee, S. (2011) Immobilization of proteins by non-coding RNA. Mol. Cell 45:147-157
-See "Translation under hypoxia" Nature Struct. Mol. Biol. 19:602
-See AACR Editorial (2012) "HIF-2a mediates hypoxia-inducible translation"
- Franovic, A., Holterman, C., and Lee, S. (2009) Human cancers converge at the HIF-2a oncogenic axis. Proc. Natl. Acad. Sci USA (track II) 106:21306-21311
- Citation in Faculty of 1000 for exceptional conceptual advance in the field
- Khacho, M., Mekhail, K., Pilon-Larose, K., Payette, J., and Lee, S. (2008) Cancer-causing mutations in the novel transcription-dependent nuclear export motif of VHL abrogates oxygen-dependent degradation of HIF. Mol. Cell. Biol. 28:302-314.
- Franovic, A., Gunaratnam, L., Smith, K., Robert, I., Patten, D., and Lee, S. (2007) Translation upregulation of EGFR by hypoxia provides a non-mutational explanation for its overexpression in human cancer. Proc. Natl. Acad. Sci USA (track II) 104:13092-13097.
- Mekhail, K., Khacho, M., Carrigan, A, Hache, R. J., Gunaratnam, L., and Lee, S. (2005) Regulation of ubiquitin ligase dynamics by the nucleolus. J. Cell. Biol. 170:733-744.
- Citation in Faculty of 1000 for exceptional conceptual advance in the field.
- See “Bound and Gagged” Nature 437:298.
- See “Hiding Proteins in the Nucleolus: J. Cell. Biol. 170:696.
- Mekhail, K., Gunaratnam, L., Bonicalzi, M. E. and Lee, S. (2004) HIF activation by pH-dependent nucleolar sequestration of VHL. Nature Cell. Biol. 6: 642-647.
- Four (4) citations in Faculty of 1000.
- Nature Paper of the Month in Stress Signaling.
- See "Policing Cells Under Stress: Noncoding RNAs Capture Proteins in Nucleolus Detention Centers" Mol. Cell 45:141-142
- Two Citations in Faculty of 1000 for exceptional conceptual advance in the field
Last updated on: June 11, 2012 9:08