Jérôme Lamartine : MELODI
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Jérôme Lamartine : jerome.lamartine@univ-lyon1.fr
Leading
the
research
group:
Collaborators:
Epiderm,
Stress
and
Differen1a1on
group
Michèle
Mar4n
(Evry)
(CGMC,
CNRS
UMR5534-‐
Univ
Lyon
I)
Walid
Rachidi
(Grenoble)
Ingrid
Masse
Xavier
Gidrol
(Grenoble)
Odile
Berthier-‐Vergnes
Slimane
Ait-‐Si-‐Ali
(Paris)
Lae44a
Barbollat
Odile
Damour
(Lyon)
Choua
Ya
Nicolas
Foray
(Lyon)
Gweltaz
Agaesse
Yves
Poumay
(Lowen,
Bel)
Aurora
Pignata
Taku
Tadeshi
(Tokyo,
Jap)
Morgane
Monchanin
Jérôme
Lamar1ne
Financial
supports:
A research group part of the CGphiMC institute Center for Molecular and Cellular Gene1cs & Physiology (CGphiMC) 14 research groups, more than 120 staff scien1sts and students Various model of study : human cells and 4ssues, mouse, drosophila, nematode …
Understanding the effect of ionizing radiations (IR) in skin
Epidermis: main target of radiocarcinogenesis
squamous Basal cell
cell
carcinoma
carcinoma
angiosarcoma
trichoepithelioma fibrosarcoma
trichoblastic carcinoma
Epidermal cells (keratinocytes) strongly respond to
low dose IR
10
mGy
2
Gy
213
270
369
Genes
responding
to
ionizing
radia4ons
(3h-‐72h)
FC
>
1.5
pvalue
Identifying biomarkers of radiation exposure easily
detectable in human skin
Non-‐invasive
cell
sampling
Over-‐exposi4on
(Tape
Stripping)
detec4on
Biomarker
analysis
Personalized follow-up of irradiated patients
Our model of study : 2D or 3D human epidermis
2D-‐culture
3D-‐culture
Ca
diff
Reconstructed
skin
Skin biopsies x25
Primary human
keratinocytes &
fibroblasts
Normal skin Hyper-radiosensitive
patients
Normal vs reconstructed skin
Normal
human
skin
Reconstructed
skin
Epidermis
DEJ
Dermis
x25 x25
The
3-‐D
model
is
very
similar
to
the
normal
4ssue
Engineering skin cells with specific gene modulation
leading to radiation sensitivity
from hypersensitive patients …
…to genes of hypersensitivity
Patched1, Gli1/2
Collabora4on
Michèle
Mar4n’s
lab
:
CEA,
FR
Gorlin syndrome: deregulation
hypersensitivity of the SHH pathway:
and carcinoma Patched1 receptor
susceptibility and Gli transcription
factors
A model of reconstructed skin with radiosensitive cells:
amplification of cellular response after low dose IR
Normal
or
Radiosensi4ve
kera4nocytes
(PTCH
mt,
Sh
PTCH1,
GLIOE)
Normal
or
Radiosensi4ve
fibroblasts
(PTCH
mt,
Sh
PTCH1,
GLIOE)
x25
Extensive use of genomic approaches
DNA microarrays Next generation sequencing High-throughput
QPCR
To
caracterize
the
transcriptome,
methylome,
miRnome
of
irradiated
skin
models
Lamar-ne
et
al.
J
Cell
Biochem
2005
Franco
et
al.
2005
Rad
Res
2005
Bagdoyan
et
al.
J
Biol
Chem
2005
Bonin
et
al.
BMC
Genomics
2009
Joly-‐Tonne-
et
al.
BMC
Genomics
2013
Specific interest in epigenetic effects of IR : microRNAs
MicroRNA
induc4on
in
irradiated
skin
MicroRNA
responding
to
10
mGy
Ctrl
probe
MicroRNA
probe
in
human
kera4nocytes
0 Gy
6 Gy
48h
Joly-‐Tonne-
et
al.
BMC
Genomics
2013
Specific interest in epigenetic effects of IR: methylation
marks
LOWRADSENSOR projet : Low dose effects, markers
and signature
Transcriptome
Methylome
IR
10
mGy
Long
term-‐effects
Cutaneous
cells
from
radiosensi4ve
pa4ents
Radiosensi4vity
signature
Control
Cells
Func4onal
proper4es,
molecular
markers
Looking
for
collabora4ons
….
(My
Ins-tu-on
is
not
a
member
of
the
OPERRA
consor-um)
Jerome.lamar1ne@univ-‐lyon1.fr
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