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Richard Béliveau

Richard Béliveau

Professor, Department of Chemistry, UQAM; Adjoint professor, Department of Physiology, Université de Montréal
Director, Laboratory of Molecular Medicine, Hôpital Ste-Justine

Address
Department of Chemistry – Biochemistry
UQAM
P.O. Box 8888, Station Centre-Ville
Montreal, Quebec H3C 3P8

Tel.: 514-987-3000 ext. 8551
Fax: 514-987-0246
beliveau [dot] richard [at] uqam [dot] ca (Email)
Dr. Béliveau's Website

Expertise: Molecular Studies on Blood-Brain Solute Exchanges; Angiogenesis: molecular studies of tumor neovascularization; Matrix metalloproteinases (MMPs) and vascular diseases; Prevention and treatment of cancer by nutratherapy

Summary of Research Activities
Dr. Richard Béliveau obtained his PhD from Université Laval and went on to complete his post-doctoral training at Cornell University in New York. He holds the Chair for Cancer Prevention and Treatment at Université du Québec à Montréal and has been a Professor in its Biochemistry department since 1984. He is the author of over 300 communications and 183 scientific articles in several journals including Lancet, Blood, Journal of Biological Chemistry and Cancer Research. To date, he has mentored close to 30 PhD and 70 Master students. He is also an associate professor in the Department of Surgery at Université de Montréal.

Dr. Beliveau has been director of the Molecular Medicine Laboratory at Ste Justine Hospital since 1996. He is also a member of the Department of Hemato-Oncology at Ste Justine, of the Neurosurgery-Oncology division at the CHUM and of the MCETC at the SMBD-Jewish General Hospital.

Recipient of approximately forty grants throughout his career, he is currently funded by NSERC, CIHR, the Cancer Research Society, the Charles-Bruneau Foundation and the UQAM Foundation.

The fight against cancer is at the heart of Dr. Beliveau’s scientific and humanitarian concerns. His team, comprised of 35 people, works on 3 main projects: Brain tumors and the blood-brain barrier, tumor vascularization (angiogenesis) and the prevention of cancer through nutrition (nutraceuticals).

RESEARCH PROJECTS:
Brain Tumors and the Blood-Brain Barrier
Brain tumors, unfortunately, do not respond to any known treatment. The blood-brain barrier performs a neuroprotective function by tightly controlling access to the brain; consequently it also impedes access of proteins as well as pharmacological agents to cerebral tissues. In order to treat brain tumors, it is therefore imperative to find vectors that can penetrate the blood–brain barrier and permit medications to do their part. We have recently shown that melanotransferrin is one such vector. We are currently studying the possibility of employing melanotransferrin as a new delivery system to target drugs directly to the brain.

Another major obstacle in the treatment of all types of cancer is the phenomenon of multiple drug resistance associated with an increase in P-glycoprotein, a protein transporter which shuttles drugs out of the cell. This protein is strongly expressed in cerebral capillaries, thereby increasing the impermeability of the blood-brain barrier to pharmacological agents. Our laboratory studies P-glycoprotein’s mode of action and its interaction with other proteins, such as caveolin, in order to establish its biological function at the level of cerebral capillaries for the treatment of brain tumors.

Tumor Vascularization (Angiogenesis)
In order to develop, a tumor activates the proliferation of blood vessels. Angiogenesis is the formation of new blood vessels from pre-existing blood vessels. This phenomenon is essential for the survival of cancer cells. Once a tumor has reached 1mm in size, the cells in the center of the tumor die due to lack of oxygen and nutrients. The formation of new blood vessels permits the tumor to continue growing. It has now been established that the aggressive growth of a tumor and the formation of metastases are directly dependent upon angiogenesis. An anti-angiogenesis approach to cancer therapy is therefore of great interest. Our laboratory is currently studying 3 aspects of tumor angiogenesis: The regulation of signalling pathways dependant upon vascular endothelial growth factor (VEGF), the role of matrix metalloproteinases (MMPs) known to be activated upon angiogenesis and tumor invasion and finally, the identification, through proteomics, of endothelial proteins associated with tumor growth.

Cancer Prevention Through Nutrition (Nutraceuticals)
We currently estimate that lifestyle and nutrition are responsible for more than one third of newly diagnosed cancers. These statistics underline the importance of healthy eating for the reduction in the incidence, as well as the progression of cancer. Throughout the years, several fundamental clinical and epidemiological studies have shown that an increased intake of fruits and vegetables represents a key factor in the reduction of cancer risk. Indeed, these products contain important quantities of non-nutritive chemical compounds, phytochemicals, which seem to play an important role in this chemopreventive effect. Other than fruits and vegetables, recent research in our lab has shown that other foods, such as green tea and curcumin, possess large quantities of anticancer compounds. A diet consisting of a mix of fruits, vegetables and drinks, such as green tea, can lead to the absorption of up to 1-2g of anticancer phytochemicals per day. We, therefore, believe that daily consumption of these different foods is a simple and effective method to counter the development and progression of cancer.

Recent Publications
Desrosiers RR, Beaulieu E,Buchanan M, Beliveau R. Proteomic analysis of human plasma proteins by two-dimensional gel electrophoresis and by antibody arrays following depletion of high-abundance proteins. Cell Biochem Biophys. 2007;49(3):182-95. Epub 2007 Oct 9.

Michaud-Levesque J, Demeule M, Beliveau R. Plasminogen-dependent internalization of soluble melanotransferrin involves the low-density lipoprotein receptor-related protein and annexin II. Biol Chem. 2007 Jul;388(7):747-54.

Langlois S, Nyalendo C, Di Tomasso G, Labrecque L, Roghi C, Murphy G, Gingras D, Beliveau R. Membrane-type 1 matrix metalloproteinase stimulates cell migration through epidermal growth factor receptor transactivation. Mol Cancer Res. 2007 Jun;5(6):569-83. Epub 2007 May 31.

Ratel D, Mihoubi S, Beaulieu E, Durocher Y, Rivard GE, Gingras D, Beliveau R. VEGF increases the fibrinolytic activity of endothelial cells within fibrin matrices: Involvement of VEGFR-2, tissue type plasminogen activator and matrix metalloproteinases. Thromb Res. 2007 May 18; [Epub ahead of print]

Rolland Y, Demeule M, Michaud-Levesque J, Beliveau R. Inhibition of tumor growth by a truncated and soluble form of melanotransferrin. Exp Cell Res. 2007 Apr 14; [Epub ahead of print]

Boivin D, Blanchette M, Barrette S, Moghrabi A, Beliveau R. Inhibition of cancer cell proliferation and suppression of TNF-induced activation of NFkappaB by edible berry juice. Anticancer Res. 2007 Mar-Apr;27(2):937-48.

Nyalendo C, Michaud M, Beaulieu E, Roghi C, Murphy G, Gingras D, Beliveau R. Src-dependent phosphorylation of membrane-type 1 matrix metalloproteinase on cytoplasmic tyrosine 573: Role in endothelial and tumor cell migration. J Biol Chem. 2007 May 25;282(21):15690-15699. Epub 2007 Mar 27.

Barakat S, Demeule M, Pilorget A, Regina A, Gingras D, Baggetto LG, Beliveau R. Modulation of p-glycoprotein function by caveolin-1 phosphorylation. J Neurochem. 2007 Apr;101(1):1-8. Epub 2007 Feb 26.

Pilorget A, Demeule M, Barakat S, Marvaldi J, Luis J, Beliveau R. Modulation of P-glycoprotein function by sphingosine kinase-1 in brain endothelial cells. J Neurochem. 2007 Mar;100(5):1203-10.

Bertrand Y, Demeule M, Michaud-Levesque J, Béliveau R. Melanotransferrin induces human melanoma SK-Mel-28 cell invasion in vivo. Biochem Biophys Res Commun. 2007 Feb 9;353(2):418-423. Epub 2006 Dec 13.

Michaud-Levesque J, Demeule M, Béliveau R. In vivo inhibition of angiogenesis by a soluble form of melanotransferrin. Carcinogenesis. 2007 Feb;28(2):280-8. Epub 2006 Jul 20.

Lamy S, Lafleur R, Bedard V, Moghrabi A, Barrette S, Gingras D, Béliveau R. Anthocyanidins inhibit migration of glioblastoma cells: Structure-activity relationship and involvement of the plasminolytic system. J Cell Biochem. 2007 Jan 1;100(1):100-11.

McLaughlin N, Annabi B, Sik Kim K, Bahary JP, Moumdjian R, Béliveau R. The Response to Brain Tumor-Derived Growth Factors is Altered in Radioresistant Human Brain Endothelial Cells. Cancer Biol Ther. 2006 Nov;5(11):1539-45. Epub 2006 Nov 30.

McLaughlin N, Annabi B, Lachambre MP, Kim KS, Bahary JP, Moumdjian R, Béliveau R. Combined low dose ionizing radiation and green tea-derived epigallocatechin-3-gallate treatment induces human brain endothelial cells death. J Neurooncol. 2006 Nov;80(2):111-21. Epub 2006 May 19.

Annabi B, Currie JC, Moghrabi A, Béliveau R. Inhibition of HuR and MMP-9 expression in macrophage-differentiated HL-60 myeloid leukemia cells by green tea polyphenol EGCg. Leuk Res. 2006 Oct 31; [Epub ahead of print]

Bertrand Y, Demeule M, Rivard GE, Béliveau R. Stimulation of tPA-dependent provisional extracellular fibrin matrix degradation by human recombinant soluble melanotransferrin. Biochim Biophys Acta. 2006 Oct;1763(10):1024-30. Epub 2006 Aug 11

Annabi B, Currie JC, Bouzeghrane M, Dulude H, Daigneault L, Garde S, Rabbani SA, Panchal C, Wu JJ, Béliveau R. Contribution of the 37-kDa laminin receptor precursor in the anti-metastatic PSP94-derived peptide PCK3145 cell surface binding. Biochem Biophys Res Commun. 2006 Jul 21;346(1):358-66. Epub 2006 Jun 2.

Barthomeuf C, Demeule M, Grassi J, Saidkhodjaev A, Béliveau R. Conferone from Ferula schtschurowskiana enhances vinblastine cytotoxicity in MDCK- MDR1 cells by competitively inhibiting P-glycoprotein transport. Planta Med. 2006 Jun;72(7):634-9. Epub 2006 May 31.

Lamy S, Blanchette M, Michaud-Levesque J, Lafleur R, Durocher Y, Moghrabi A, Barrette S, Gingras D, Béliveau R. Delphinidin, a dietary anthocyanidin, inhibits vascular endothelial growth factor receptor-2 phosphorylation. Carcinogenesis. 2006 May;27(5):989-96. Epub 2005 Nov 23.

Rolland Y, Demeule M, Béliveau R. Melanotransferrin stimulates t-PA -dependent activation of plasminogen in endothelial cells leading to cell detachment. Biochim Biophys Acta. 2006 Apr;1763(4):393-401. Epub 2006 Apr 19.

Annabi B, Bouzeghrane M, Currie JC, Dulude H, Daigneault L, Garde S, Rabbani SA, Panchal C, Wu JJ, Béliveau R. Inhibition of MMP-9 secretion by the anti-metastatic PSP94-derived peptide PCK3145 requires cell surface laminin receptor signaling. Anticancer Drugs. 2006 Apr;17(4):429-38.