| Philippe
Brabet |
 |
Function
: CR1 INSERM
Academic and research
track :
I began my research activity in 1985 within
the Joël Bockaert’s laboratory at Montpellier
where I have participated, with Bruno Rouot and Vincent hamburger,
in studying GPCRs and G protein signal transduction in the
brain. In 1990, he have joined the team of Lutz Birnbaumer
in the Department of Cell Biology, Baylor College of Medicine,
Houston, Texas USA, where, with Uwe Rudolph, we developed
gene targeting technologies on Gi/o proteins. Back to Joël
Bockaert’s in 1992 after I was appointed by INSERM,
I have started with Françoise Jamen and Nieves Rodriguez-Henche,
working onto the VIP, PACAP receptor, generating a PACAP-preferring
receptor (PAC1R)-deficient mouse line and studying the transcriptional
regulation of PAC1R. In 2001, I have moved to Christian Hamel’s
team to discover visual cycle genes causing inherited diseases
of the retina. In 2003, he have joined the team "Genetics
and therapy of retinal blindness" and became the coordinator
of a research group onto “Inherited retinal dystrophies
and the visual cycle in the retinal pigment epithelium”.
Main achievements
:
In the late eighties, I have contributed
to the biochemical identification of G proteins in the nervous
system, and focused my interest on the most abundant Go protein,
getting insights into its cellular distribution, gene expression
patterns, metabolic regulation, and function (J neurosci.,
1988; JBC, 1989). Later, I have participated to the generation
of Gi2 and Go knockout mice, whose phenotypic analysis pointed
a role of Gi2 in immune responses and tumor suppression (Nature,
1995) and major role for Go in motor behavior and in pain
perception (PNAS, 1998). During my post-doc training and
later, I have contributed to the molecular cloning and characterization
of GPCR genes, such as the V2 receptor for the human antidiuretic
hormone, vasopressin (Nature and Am J Hum Genet, 1992), and
the PAC1 receptor for the the pituitary adenylate cyclase
activating polypeptide, PACAP (JBC and Genomics, 1996) and
I have generated other genetically modified mouse models
(JCI, 2000; J. Neurosci., 2001 and 2004; MCB, 2005).
Research interests
:
In this XXI century, I started working on the visual retinoid
cycle that is essential for regeneration of the chromophore,
11-cis retinal:
- Identifying new partners of RPE65, an enzyme catalyzing
the key step in the transformation of all-trans-retinal
to 11-cis-retinal, which is the isomerization
reaction.
- Getting insights into the molecular mechanisms that may
regulate the isomerization step.
- Developing original tools to tests gene mutation – induced
dysfunction of isomerization partners
- Supporting blind patient with mutation analysis in new
candidate genes
- Proposing new therapeutic strategies to cure inherited
retinal dystrophies
Selected publications
:
Senechal A, Humbert G, Surget MO, Bazalgette C, Bazalgette
C, Arnaud B, Arndt C, Laurent E, Brabet P, Hamel CP. Am
J Ophthalmol. 2006; 142(4):702-4.
Guignard T, Pequignot MO, Ayoub B, Weber A, Ripoll C, Hamel
C, Brabet P., ARVO 2006, abstract # 2030.
Kamei S, Chen-Kuo-Chang M, Cazevieille C, Lenaers G, Olichon
A, Belenguer P,Roussignol G, Renard N, Eybalin M, Michelin
A, Delettre C, Brabet P, Hamel CP. Invest Ophthalmol
Vis Sci. 2005; 46(11):4288-94.
Delprat B, Ruel J, Guitton MJ, Hamard G, Lenoir M, Pujol R, Puel JL, Brabet P, Hamel CP.. Mol Cell Biol. 2005; 25(2):847-53.
Jamen F, Persson K, Bertrand G, Rodriguez-Henche N, Puech
R, Bockaert J, Ahren B, Brabet P. J Clin Invest.
2000 May;105(9):1307-15.
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