Ryerson University
Department of Chemistry & Biology
350 Victoria Street
Toronto , ON
M5B-2K3
OFFICE
Telephone: 416-979-5000 Extension 4517;
Room: E328B, East Kerr Hall
Molecular Retrovirology Laboratory
Telephone: Extensions 4116 or 4117
E-mail: mestable@ryerson.ca

CROSS-APPOINTMENTS
Guelph University , School of Graduate studies (2005-Ongoing)
Guelph University Department of Chemistry (2005-Ongoing) Ryerson University School of Graduate Studies (2005-Ongoing) Ryerson University Molecular Sciences M.Sc. graduate program (2006-Ongoing)
Ryerson University Environmental Sciences Graduate program (2005-Ongoing)
IAF-INRS Visiting Scientist (2005-2007)
PEDECIBA, Grado IV Professor (2004-2007)

PEER-REVIEWING AND MEMBERSHIPS
Peer-reviewer for Nature Publishing Group (2007)
NSERC Grant reviewer (2005-2006)
Member of the AAAS
Member of the ASM
Member of SLS
Member of FUCLES

COMMITTEES
Departmental Separation Committee (2003)
Departmental Health and Safety Committee (2004)
NSERC USRA Committee (2004)
Departmental Planning Committee (2005)
Radiation Safety Committee (2005-Ongoing)  

RESEARCH GRANTS
CIHR FELLOW (1998-2001)
RU Seed Grant (2001)
RU Summer and winter Research Assistant Grants(multiple years)
CFI/OIT (2002)
Canfar (2004)
NSERC (2004-Ongoing)

After completing his Ph.D. at UBC, Dr. Estable trained in transcription research with Dr. Robert Roeder at the Rockefeller University in Manhattan , in the laboratory of Biochemistry & Molecular Biology, where he was a CIHR postdoctoral Fellow for three years.

The Molecular Retrovirology Laboratory of Dr. Estable, at Ryerson, is a P2 Laboratory, equipped for Molecular Biology, Biochemistry, Tissue Culture and DNA Sequencing. It is the only lab licensed to work with open sources of radioisotopes at Ryerson. Over his career, Dr. Estable has published work in the neurosciences, photosynthesis, microbiology, cancer, eukaryote gene regulation and virology. His current interests focus on the regulation of HIV-1 transcription. He has two active projects.

If you are a potential fourth year Thesis student, graduate student or PDF, interested in this type of research, please contact Dr. Estable at mestable@ryerson.ca , after reading the most recent publications, related to the project of interest to you (below).

If you would like to contribute financially to this type of research, please contact the Canadian Foundation for AIDS research at (http://www.canfar.com), which has funded Dr. Estable in the past; or visit the Ryerson University website for a link on how to contribute to the growth of our university.

MCEF PROJECT:

The first project is the structure/function analysis of MCEF, a protein discovered and named by Dr. Estable, for its ability to interact with a species-specific co-factor for HIV-1 transcription, termed P-TEFb. In addition to cloning the cDNA for MCEF, he has found that MCEF can repress HIV-1 replication, at the level of HIV-1 Tat-trans-activation of transcription. Current work in his lab, in 2008, focuses on mapping the repressor regions of MCEF, by mutagenesis. Dr. Estable's group also collaborates with a group at Harvard, interested in the normal function of MCEF.

TWO-TIER PEER REVIEWED PUBLICATIONS RELATED TO THE MCEF PROJECT

MCEF is localized to the nucleus by protein sequences encoded within three distinct exons, where it represses HIV-1 Tat-transactivation of LTR-directed transcription. Int J Biol Sci 2007; 3:225-236. http://www.biolsci.org/v03p0225.htm .

Mario Clemente Estable, M. Naghavi, H. Kato, H. Xiao, J. Qin, R. G. Roeder . MCEF, the newest member of the AF4 family of transcription factors involved in leukemia, is a P-TEFb-associated protein that can repress HIV-1. J. Biomed. Sciences, May-Jun. 9:234-245. 2002.

CONFERENCE ABSTRACTS RELATED TO THE MCEF PROJECT

Maksymillian Niedzielski, Robert Hopewell, Zohra Ismail, Mario C. Estable. MCEF is localized to the nucleus by protein sequences encoded by 3 exons, where it represses HIV-1 Tat-transactivation. (ASM Meeting, Abstract 07-GM-A-3631-ASM, Poster T-028, Viral Pathogenesis session. May 21-25, 2007, Toronto).

Niedzielski M., Hopewell R, Ismail Z. and Estable M.C. Full-length MCEF expresses poorly in HeLa cells, but localizes to the nucleus and down-regulates episomal HIV-1 LTR-directed transcription. CFBS meeting, Ottawa, Canada, October 2006, Poster # P12.

Niedzielski M., Mok G., Ismail Z., Azad L., Monteiro M., Liss S., Estable M.C. The MCEF nuclear localization domain and a putative PEST sequence (PPD4) map to highly conserved sequences within all AF4-family members (AFFs). AIDS 2006 - XVI International AIDS Conference, 2006 Abstract no. CDA0004

MFNLP Project:

The second project is to elucidate the function of an element within the HIV-1 LTR, named MFNLP by Dr. Estable. This region of the LTR contains a binding site, named RBEIII by Dr. Brendan Bell. RBEIII is required for full Ras-responsiveness of the HIV-1 LTR. In clinical samples from the long lasting VLAS study in Vancouver , Dr. Estable previously showed that the MFNLP recreates a binding site for a transcription factor, previously termed RBF2. Dr. Estable discovered that RBF2 is composed of USF and TFII-I, two transcription factors previously cloned in the lab of Dr. Roeder. Current work in his lab, in 2008, focuses on establishing if the RBEIII site is indeed important for live virus replication (in collaboration with a P3 facility) and designing a fusion protein strategy for blocking this site.

TWO-TIER PEER REVIEWED PUBLICATIONS RELATED TO THE MFNLP PROJECT

Mario C. Estable. In search of a function for the most frequent naturally-occurring length polymorphism (MFNLP) of the HIV-1 LTR: Retaining functional coupling of Nef and RBF-2 at RBEIII? is a target for USF and TFII-I (RBF2) cooperative binding. Int J Biol Sci 2007; 11;3(5):318-27. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17589566

J. Chen, T. Malcom, Mario C. Estable, R. G. Roeder et. al. TFII-I regulates induction of chromasomally integrated HIV-1 LTR in cooperation with USF. Journal of Virology, 2005 Apr;79(7):4396-406.

M. H. Naghavi, Mario C. Estable, S. Schwartz, R. G. Roeder , A. Vahlne. USF affects HIV-1 LTR-directed transcription in a cell-specific manner, independently of the HIV-1 subtype and core-NRE. J Gen Virol.. 82(Pt 3):547-59, Mar, 2001.

Mario Clemente Estable, et. al. Purification of RBF-2, a novel transcription factor with specificity for the most conserved cis-element of the HIV-1 LTR. J. Biomedical Sciences, Vol. 6, No. 5, 1999.

Mario Clemente Estable, et. al. A frequent naturally occurring length polymorphism of the HIV-1 LTR binds RBF-2 and represses transcription. J. Virology, Vol. 72, No. 8, 6465-74, 1998.

Mario Clemente Estable, et. al. HIV-1 LTR Variants from 42 patients representing all stages of infection display a wide range of sequence polymorphism and transcription activity. J. Virology, Vol.70, No. 6, p.4053-4062, 1996.

CONFERENCE ABSTRACTS RELATED TO THE MFNLP PROJECT

M. H. Naghavi1, M. C. Estable, S Schwartz1 , R. G. Roeder and A Vahlne. USF is a cell-specific, subtype-independent dual repressor/ activator of HIV-1 LTR-directed transcription. Keystone symposia, HIV Pathogenesis, March 28-April 3, 2001, Keystone, Colorado .

Mario Clemente Estable, et. al. HIV-1 5-LTR MFNLPs bind RBF-2 and correlate with the loss of RBF-1,2 or NFkB sites. VI Annual Canadian Conf. on HIV/AIDS, Ottawa , Ontario , May 1997.

Mario Clemente Estable, et. al. Subtypes and genetic distances for HIV-1 circulating in the VLAS and VIDUS cohorts. VI Annual Canadian Conference on HIV/AIDS Research, Ottawa , Ontario , May 1997.

M.C. Estable, et. al. HIV-1 LTRs from 42 patients representing all stages of infection, display a wide range of polymorphism in sequence, transcription potential and binding of factors but no clinical correlation. Mo.A.1023 p59, Vol 1, XI International AIDS Conference, Vancouver Canada , July 7-12 1996.

Merzouki, M.C. Estable, et. al. Sequence variability of HIV-1 ADCC epitopes in vivo V3 loop ADCC epitopes appear to be the major determinants for ADCC activity at different stages of infection. Abstract Tu.A.2056, p 274, Vol. 1, XI International AIDS Conference, Vancouver Canada , July 7-12 1996.

M.C. Estable, et. al. Polymorphic proviral Genotypes of HIV-1 5-LTR during the course of HIV-1 infection. VII International Conference of Comparative Virology Oct.12-17, 1994, Montreal , Canada . Program Synopsis p 2-20.

T. Mo, M. OShaughnessy, A. Merzouki, M. Estable, et. al. Accurate differential quantification of HIV-1 tat, rev, nef and pol mRNAs in patients with early stage infection. X International AIDS Conference. Yokohama Japan , 7-12 August, 1994. Abstract book Volume 1, p15: 354A.

Andrew E. Laursen, Charles F. Kulpa, Sophia Y. Dore, Maksymilian Niedzielski, and Mario C. Estable. Newly isolated thermotolerant and thermophilic bacteria capable of using methane as a sole source of carbon and energy. JEES, 2007, In Press.

EstherLeng, Georgia Tai, Mario Estable, et. al. Organization and expression of the Cyr61 gene in normal human fibroblasts. J. Biomedical Sciences, Jan-Feb;9 (1):59-67.2002.

Mario Clemente Estable, et. al. Distinct clustering of injection drug user-derived HIV-1 versus non-injection drug user-derived sequences in Vancouver . AIDS Research and Human Retroviruses, Vol. 14, No. 10. 917-9, 1998.

Juan F. Estable-Puig, Rosita Ferrero Estable-Puig, Mario Clemente Estable. Patologia de la enfermedad de Alzheimer (Spanish). Proceedings of the VII Panamarican Congress of Neurology, Montevideo Uruguay . p. 211-219, 1995.

Merzouki, et. al, Mario Estable, at. al. Accurate and differential quantitation of HIV-1 tat, rev and nef mRNAs by competitive PCR. J. Virological Methods 50: 115-128, 1994.

S. Cassol, Mario Estable, et. al. Monitoring genetic variation in HIV-1 field strains by direct sequencing of dried blood spot specimens: Implications for vaccine development. Retroviruses of Humans AIDS and Related Animal Diseases, Edited by Marc Girard, Louis Valette: I.D.M.M. press 6957 DARDILLY, Paris, France.p.75-78. Cent Gardes, 1994.

D. Bernier, et.al, M. Estable-Puig, et. al. Functional analysis of developmentally regulated Chromatin-Hypersensitive Domains Carrying the -Fetoprotein Gene Promoter and the Albumin/ -Fetoprotein Intergenic Enhancer. Molecular and Cellular Biology, Vol. 13, No. 3, p.1619-1633, 1993.

R.F.de Estable-Puig, J.F. Estable-Puig and M. C. Estable. Leptomeningeal Cysts after spot Freezing: Transmission and scanning Electron Microscopy Observations. Experimental Pathology, Vol.30. pp.181-188, 1987.

R.F. de Estable-Puig, J.F. Estable-Puig and M.C. Estable. Solitary Abscess in Rat Brain: Light and Electron Microscopy observations. Experimental Pathology, Vol.30, pp.47-50, 1986.

R.F.de Estable-Puig, J.F.Estable-Puig y M.C.Estable. Respuesta lesional de la superficie de los ventriculos laterales a la congelacion focal cerebral en la rata. Patologia 18:485-492,1985.

Mario Estable, Francois Paradis et Guy Bellemare. La sedimentation isopycnique sur gradient de Percoll: une nouvelle technique disolement des minicellules. (French) "Isopicnic sedimentation in Percoll gradients: a new technique for the isolation of minicells". Association Canadienne Francais pour l'Avancement de la Science. Universite de Chicoutimi. Annales de LACFAS. Volume 52-53, No.1, 1985.

Laursen, C.F. Kulpa, S.Y. Dore, M.F. Niedzielski, M.C. Estable. Bioprospecting for thermophilic or thermotolerant methanotrophs in Yellowstone National Park , USA ; CSM Poster. June 21, Annual 2006 CSM meeting, A37 Poster. Bacterial 16s rRNA

Mario Clemente Estable Ferrero . A cis-element absolutely required for HIV-1 pathogenesis and purification of its trans-acting factor RBF-2. Ph.D. Thesis, University of British Columbia, Department of Pathology 1998 (defense date 24th April 1998).

Mario Clemente Estable-Ferrero . Caracterisation, localisation et identification de Genes sur deux fragments de DNA Chloroplastique de C. M. (French). M.Sc. These, Universite Laval, 1987.

NEWS ARTICLE

Danielle Grogan. Slowing down a killer virus. Impact. January 2006.

Terry Schonberger. Ryerson looks to cure AIDS, The Eye Opener. Volume 39, Issue 25, 11/30/04.

Stephen Huebl . Ryerson ready for radiation. The Eye Opener, Volume 39, Issue 25, 01/22/03.

Diane Luckow. Power secure for researchers. SFU News., vol. 28, no. 7, 11/ 27/03.

Sutton Eaves. Life without Mother. The Eye Opener, Volume 39, Issue 25, 10/02/02.

NEWSLETTERS

Estable M. , Report from the lab. Catalyst CANFAR Newsletter, p1, 2004

Cassol S., Estable M. , MO T., Merzouki A., Vellani N., Pattulo A., Sy T., Edmeston J., Strumpfer A., OShaughnessy M. New insights into HIV-1 replication and transmission: implications for therapeutic intervention. Canadian Association of Clinical Microbiology and Infectious Disease Newsletter, No. 9, 1994.

Bellemare G., Estable M.C. , Paradis F. Minicell Isolation by Isopicnic sedimentation in gradients of silica: Protocol. Analects Pharmacia : Molecular Biology Division. Vol.14, pp1-4, 1986.

Mario C. Estable. Two Aspects of HIV-1 Transcription: The components of RBF2 and P-TEFb. Karolinska Institute, January 2001.

Mario C. Estable. Human DNA Sequence polymorphisms of the proviral HIV-1 LTR. Rockefeller University, June 1998.

Mario C. Estable. Human DNA Sequence polymorphisms of the proviral HIV-1 LTR. Invited speaker to the Salk Institute, May 1998.

Ivan J. Sadowski, Brendan Bell and Mario Estable. The HIV-1 proviral LTR and Transcription. Virology Study Group, UBC, 1995.

Mario Estable. The fluorescent DNA Laboratory: Automated DNA Sequencing and fragment sizing. Guest speaker representing ABI. Universities of Alberta, Calgary, McGill, Vancouver, Victoria, 1992.

Mario Estable. Automated Sequencing and Applied Biosystems: An overview. Guest Speaker, representing Applied Biosystems. University of Victoria CFBS Automated DNA Sequencing workshop, 1992.

Mario Estable. Automated capillary electrophoresis. Guest speaker representing Applied Biosystems. Universities of Alberta, Calgary, Vancouver, Montreal, Ottawa, Laval, Toronto and Connaught Laboratories, 1992.

Mario Estable. High performance Electrophoretic chromatography. Guest Speaker epresenting Applied Biosystems. Universities of Halifax, Alberta, Calgary, McGill, Laval, Toronto, Vancouver., 1991.

Mario C. Estable & Robert G. Roeder . MCEF, A NOVEL TRANSCRIPTION FACTOR. Filed in 2001, published in 2003 USPTO.

DNA SEQUENCES PUBLISHED IN GENBANK

GenBank DQ208687. Geobacillus stearothermophilus 16S ribosomal RNA gene.
GenBank DQ208686. Brevibacillus agri 16S ribosomal RNA gene.
GenBank DQ208685. Brevibacillus agri 16S ribosomal RNA gene.
AF213987.1 and AF213987.2 Homo sapiens MCEF protein (MCEF) mRNA, complete cds.
AF307860. Homo sapiens CYR61 protein (CYR61) gene, complete cds.
AF058090 to AF058173. Series of 83 sequences from Canadian patients.
U72074 to U72140. Series of 56 cloned sequences from Canadian patients.