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Hélène Paradis

BioMedical Sciences
B.Sc., Ph.D. Montreal

Professor of Vascular Molecular Biology/Pediatric Cancers

Room: 5360/5356, HSC

t: 709-864-6011
f: 709-864-6007
lab: lab: 709-864-6005

hparadis@mun.ca


From Development and Pediatric Cancers to Aging and Vascular Diseases

In the quest of identifying novel proteins regulating angiogenesis and cancer, our laboratory has characterized Tubedown-1 (Tbdn-1). Tbdn-1 is one of the mammalian homologues of the yeast acetyltransferase subunit NAT1 and co-purifies with an acetyltransferase activity. Tbdn-1 is highly expressed during embryogenesis, but postnatally, high levels become restricted to discrete cells of the bone marrow and to few specialized endothelial tissues including the atrial endocardium, ocular blood vessels and blood vessels of regressing ovarian follicles. Tbdn-1 is also present at high level in some pediatric cancers. For the past few years our research group has devoted its efforts to further characterize the role of Tbdn-1 in blood vessels and pediatric cancers.

Our recent studies have shown that Tbdn-1 inhibits angiogenesis in vitro and that its expression is specifically suppressed in retinal endothelial cells from patients suffering from proliferative diabetic retinopathy which is characterized by neovascular overgrowth. Our results suggest that Tbdn-1 is important for maintaining retinal blood vessel homeostasis and consequently for preventing vision loss resulting from neovascularization. Our current objectives are to gain further insights into the regulation and signaling pathway of this important protein with the overall goal of maintaining its expression or activity in retinal blood vessels during proliferative retinopathies. In doing so, better treatments and improved quality of life may be tangible for the millions of people world wide afflicted with proliferative retinopathies including diabetic retinopathy, macular degeneration (which occurs in older patients), and retinopathy of prematurity in newborns.

In another cellular context, Tbdn-1 is found at levels higher than normal in a subset of pediatric tumors (Figure 1). Current treatments for several pediatric cancers rely heavily on chemotherapeutic approaches that can be highly toxic and unsuccessful. Treatments targeting more specific molecular targets are needed to decrease the toxicity and improve the quality of life of the patients. Our current objectives are to gain further insights into the signaling pathway and the role of Tbdn-1 in pediatric cancers that express high levels of tbdn-1. Our characterization of the role of Tbdn-1 in pediatric bone tumor cells suggests that it regulates the growth and differentiation of these types of tumors and that it could represent a target for designing new and improved treatments.

Biographical Information:

Doctorate: 1986-1991, University of Montreal, Molecular Biology.

 Post-Doctoral Training: 1991-1994, Harvard Medical School, Dana Farber Cancer Institute, Signal Transduction.

RECENT INVITED PRESENTATIONS:

Paradis, H., Martin, D., Wall, D.S., Zwerdling, T., Martin, E., Inge, T., Collins, M., M.,Witte, D.P., Alonzo, T., Good, W.V., Lui, C.-Y., Kao, W.W.-Y., and Gendron, R.L. The role of Tubedown-1 in different cellular context, from retinal vessels to pediatric cancers. (2003) The Bascom Palmer Eye Institute, University of Miami, Miami, FL.

Paradis, H., Martin, D., Wall, D.S., Zwerdling, T., Martin, E., Inge, T., Collins, M., M.,Witte, D.P., Alonzo, T., Good, W.V., and Gendron, R.L. Tubedown-1, a key player in diabetic retinopathy and pediatric cancers. (2003) Biochemistry Seminars, Memorial University of Newfoundland, St.John's, NL.

PAST AND CURRENT GRANT SUPPORT:

1999 - 2002 National Institutes of Health, National Eye Institute, R01-EY12827 (PAR-98-096).

2000 - 2002 Children’s Oncology Group Chairman’s Award (National Institute of Health, National Cancer Institute, U10-CA13539).

2002 - 2005 Canadian Institutes of Health Research, Operating grant, Institute of Circulatory and Respiratory Health, MOP-53112.

2002 - 2005 Canadian Institutes of Health Research/Regional Partnership, Operating grant, Institute for Cancer Research, ROP-58913.

2002 - 2005 Foundation Fighting Blindness Canada Operating grant.

2003 - 2007 Canadian Foundation for Innovation; New Opportunities Fund.

2003 - 2005 Grant-in-Aid, Smith Kettlewell Eye Research Institute.
 


Current Members of our Research Group:

(Co-supervised with Dr. Robert Gendron)

Adam Green (Ph.D. Candidate Graduate Student)

Darryl Martin (Ph.D. Candidate Graduate Student)

Dana Wall (M.Sc. Candidate Graduate Student)

Karina LeBlanc M.Sc. (Research Assistant)

Ewa Miskiewicz, Ph.D. (Research Assistant)

Stephanie Tucker M.Sc. (Research Assistant)

 


SELECTED PUBLICATIONS:

Paradis, H., Arceci, R.J., Adams, L.C., and Gendron, R.L.

Differentiation responses of embryonic endothelium to leukemia inhibitory factor. (1998) Exp. Cell Res. 240, 7-15.

Gendron, R.L., Adams, L.C., and Paradis, H.

Tubedown-1: A novel acetyltransferase associated blood vessel development. (2000) Dev. Dyn. 218, 300-315.

Paradis, H., and Gendron, R.L.

LIF transduces contradictory signals on capillary outgrowth through induction of Stat3 and P41/43MAP kinase. (2000) J. Cell Sci. 113, 4331-4339.

Gendron, R.L., Good, W.V., Adams, L.C., and. Paradis, H.

Expression of tubedown-1 is suppressed in retinal neovascularization of proliferative diabetic retinopathy. (2001) Invest. Opthalmol. Vis. Sci. 42, 3000-3007.

Paradis, H., Liu, C.-Y., Saika, S., Azhar, M., Doetschman, T., Good, W.V., Nayak, R., Laver, N., Kao, C.W.-C., Kao, W.W.-Y, and Gendron, R.L.

Tubedown-1 in remodeling of the developing vitreal vasculature in vivo and regulation of capillary outgrowth in vitro. (2002) Dev. Biol. 249, 140-155.
 

 
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