The Journal of Experimental Medicine,
Journal Year:
2024,
Volume and Issue:
221(9)
Published: July 2, 2024
Gain-of-function
mutations
in
STING
cause
STING-associated
vasculopathy
with
onset
infancy
(SAVI)
characterized
by
early-onset
systemic
inflammation,
skin
vasculopathy,
and
interstitial
lung
disease.
Here,
we
report
characterize
a
novel
variant
(F269S)
identified
SAVI
patient.
Single-cell
transcriptomics
of
patient
bone
marrow
revealed
spontaneous
activation
interferon
(IFN)
inflammatory
pathways
across
cell
types
striking
prevalence
circulating
naïve
T
cells
was
observed.
Inducible
F269S
expression
conferred
enhanced
signaling
through
ligand-independent
translocation
the
protein
to
Golgi,
protecting
from
viral
infections
but
preventing
their
efficient
immune
priming.
Additionally,
endothelial
promoted
further
exacerbated
cytokine
secretion
cells,
resulting
inflammation
damage.
Our
findings
identify
mutation
as
pathogenic
causing
SAVI,
highlight
importance
crosstalk
between
context
disease,
contribute
better
understanding
how
aberrant
can
pathology.
Protein Science,
Journal Year:
2020,
Volume and Issue:
30(1), P. 218 - 233
Published: Nov. 4, 2020
Abstract
For
a
complete
understanding
of
system's
processes
and
each
protein's
role
in
health
disease,
it
is
essential
to
study
protein
expression
with
spatial
resolution,
as
the
exact
location
proteins
at
tissue,
cellular,
or
subcellular
levels
tightly
linked
function.
The
Human
Protein
Atlas
(HPA)
project
large‐scale
initiative
aiming
mapping
entire
human
proteome
using
antibody‐based
proteomics
integration
various
other
omics
technologies.
publicly
available
knowledge
resource
www.proteinatlas.org
one
world's
most
visited
biological
databases
has
been
extensively
updated
during
last
few
years.
current
version
divided
into
six
main
sections,
focusing
on
particular
aspects
proteome:
(a)
Tissue
showing
distribution
across
all
major
tissues
organs
body;
(b)
Cell
localization
single
cells;
(c)
Pathology
impact
survival
patients
cancer;
(d)
Blood
profiles
blood
cells
actively
secreted
proteins;
(e)
Brain
human,
mouse,
pig
brain;
(f)
Metabolic
involvement
metabolism.
HPA
constitutes
an
important
for
further
biology,
datasets
hold
much
promise
emerging
efforts
cell
analyses,
both
transcriptomic
proteomic
level.
Molecular Cancer,
Journal Year:
2021,
Volume and Issue:
20(1)
Published: March 19, 2021
Abstract
Lung
cancer
(LC)
is
a
heterogeneous
disease
consisting
mainly
of
two
subtypes,
non-small
cell
lung
(NSCLC)
and
small
(SCLC),
remains
the
leading
cause
death
worldwide.
Despite
recent
advances
in
therapies,
overall
5-year
survival
rate
LC
less
than
20%.
The
efficacy
current
therapeutic
approaches
compromised
by
inherent
or
acquired
drug-resistance
severe
off-target
effects.
Therefore,
identification
development
innovative
effective
are
critically
desired
for
LC.
RNA-mediated
gene
inhibition
technologies
was
turning
point
field
RNA
biology.
critical
regulatory
role
different
RNAs
multiple
pathways
makes
them
rich
source
targets
tools
developing
anticancer
therapies.
antisense
sequences,
short
interfering
(siRNAs),
microRNAs
(miRNAs
miRs),
anti-miRs,
mRNA-based
platforms
holds
great
promise
preclinical
early
clinical
evaluation
against
In
last
decade,
RNA-based
therapies
have
substantially
expanded
tested
trials
malignancies,
including
This
article
describes
understanding
various
aspects
therapeutics,
modern
platforms,
modifications,
combinations
with
chemo-/immunotherapies
that
translational
potential
Science Advances,
Journal Year:
2022,
Volume and Issue:
8(2)
Published: Jan. 14, 2022
In
situ
spatial
proteomics
analysis
of
a
single
cell
has
not
been
achieved
yet,
mainly
because
insufficient
throughput
and
sensitivity
current
techniques.
Recent
progress
on
immuno-nucleic
acid
amplification
technology
presents
tremendous
opportunities
to
address
this
issue.
Here,
we
report
an
innovative
hybridization
chain
reaction
(HCR)
technique
that
involves
computer-aided
design
(CAD)
reversible
assembly.
CAD
enables
highly
multiplexed
HCR
with
sequence
database
can
work
in
parallel,
while
assembly
the
switching
between
working
state
resting
state.
Thus,
CAD-HCR
successfully
adopted
for
single-cell
analysis.
The
fluorescence
signal
is
comparable
conventional
immunofluorescence,
it
positively
correlated
abundance
target
proteins,
which
beneficial
visualization
proteins.
method
developed
here
expands
toolbox
studies,
as
well
performance
application
HCR.
Protein Science,
Journal Year:
2023,
Volume and Issue:
32(2)
Published: Jan. 6, 2023
Studying
the
spatial
distribution
of
proteins
provides
basis
for
understanding
biology,
molecular
repertoire,
and
architecture
every
human
cell.
The
Human
Protein
Atlas
(HPA)
has
grown
into
one
world's
largest
biological
databases,
in
most
recent
version,
a
major
update
structure
database
was
performed.
data
now
been
organized
10
different
comprehensive
sections,
each
summarizing
aspects
proteome
protein-coding
genes.
In
particular,
large
datasets
with
information
on
single
cell
type
level
have
integrated,
refining
tissue
specificity
detailing
expression
states
an
increased
resolution.
multi-modal
constitute
important
resource
both
basic
translational
science,
hold
promise
integration
novel
emerging
technologies
at
protein
RNA
level.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: March 7, 2024
Abstract
Vertebrates
transport
hydrophobic
triglycerides
through
the
circulatory
system
by
packaging
them
within
amphipathic
particles
called
Triglyceride-Rich
Lipoproteins.
Yet,
it
remains
largely
unknown
how
are
loaded
onto
these
particles.
Mutations
in
Phospholipase
A2
group
12B
(
PLA2G12B)
known
to
disrupt
lipoprotein
homeostasis,
but
its
mechanistic
role
this
process
unclear.
Here
we
report
that
PLA2G12B
channels
lipids
lumen
of
endoplasmic
reticulum
into
nascent
lipoproteins.
This
activity
promotes
efficient
lipid
secretion
while
preventing
excess
accumulation
intracellular
lipids.
We
characterize
functional
domains,
subcellular
localization,
and
interacting
partners
PLA2G12B,
demonstrating
is
calcium-dependent
tightly
associated
with
membrane
reticulum.
also
detect
profound
resistance
atherosclerosis
mutant
mice,
suggesting
an
evolutionary
tradeoff
between
triglyceride
cardiovascular
disease
risk.
identify
as
a
key
driver
incorporation
vertebrate
Cell Reports,
Journal Year:
2024,
Volume and Issue:
43(4), P. 114114 - 114114
Published: April 1, 2024
Patients
afflicted
with
Stimulator
of
interferon
gene
(STING)
gain-of-function
mutations
frequently
present
debilitating
interstitial
lung
disease
(ILD)
that
is
recapitulated
in
mice
expressing
the
STING
