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Biomedical research to improve

the lives of people


with Down syndrome
Tom Blumenthal, PhD
Executive Director
Anna and John J. Sie Professor in Genomics
University of Colorado School of Medicine

A network of affiliate organizations working together


to improve the lives of people with Down syndrome

When the whole is greater than the sum of the parts

Dr. Tom Blumenthal


Executive Director

Dr. Fran Hickey


Director

Michelle Sie Whitten


President and CEO

Dr. Huntington Potter


Director

Working in coordination with its affiliate organizations, the Crnic Institute is


constantly updated of developments at the medical care facilities
and the community at large.

Our strategy
To attract the best and brightest from other
research fields and induce them to perform
research on Down syndrome
We achieve this by creating competitive funding
mechanisms to support the best science and the
best scientists at every stage of their career
We have created the following funding
mechanisms:
1. Grand Challenges Grants for Principal Investigators
2. Doctoral and Post-doctoral Fellowships
3. Undergraduate Internships

The first academic home for Down syndrome research


34 research teams, 100+ scientists, one common goal:
Improve the lives of people with Down syndrome
Intramural

Blumenthal

Espinosa

Potter

Biochemistry and Mol. Genetics

Pharmacology

Neurology

Gardiner

Yeager

Pediatrics

Pediatrics/Bioengineering

Extramural
University of Colorado Anschutz Medical Campus
Pediatrics

Biochemistry and Mol. Genetics

Shaikh McLean
Spritz

Hickey

Pharmacology

Immunology

Cel. Dev. Biology

DeGregori

Liu

Kennedy

Perraud

Pearson

Johnson

Hansen

Sullivan

Neurology

Dermatology

DellAcqua

Bettcher

Bilousova

Porter

University of Colorado Boulder


Molecular, Cellular and Developmental Biology

Integrative Physiology

Dowell

Yi

Klymkoswky

Link

Psychology

Old

Olwin

Chen

Hoeffer

Maier

Junge

Xue

Jones

Stitzel

The largest geographical cluster of scientists


investigating Down syndrome
5 Research Teams within the Institute
29 Additional Research Teams
2 campuses
11 academic departments
Anschutz Medical Campus
34 miles

Boulder Campus

Collaborative, Multidisciplinary, Integrative

Alzheimers research at the Crnic Institute


Huntington Potter, PhD
Currently performing clinical
trials to test the efficacy of the
protein GMCSF in the treatment
of Alzheimers disease

Brianne Bettcher
Investigating the role of
inflammation in cognitive
decline and progression of
Alzheimers disease.

Matthew Kennedy, PhD


Investigates how increased betaamyloid production causes loss of
neuron function to find targets for
future therapies

Ding Xue, PhD


Studies the role of the protein
presenilin in the production of
beta-amyloid for the design of
novel treatments for Alzheimers
in people with Down syndrome

Mark DellAcqua, PhD


Studies the role of of calcium
signaling in inhibition of neuronal
function by beta-amyloid plaques
in Down syndrome

Charles
AA..Hoeffer,
Charles
Hoeffer,
PhD
Charles
Hoeffer,Ph.D.
Ph.D.

Anesthesia
&&Down
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Anesthesia
Downsyndrom
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Investigates
the
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of the
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TeRCAN1
st theideathatgene
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on
on
ch
rom
osom
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rom
ote
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Alzheimers disease-related
neuropathology

These research projects have the potential to reveal novel approaches for
early detection and treatment of Alzheimers disease.

Research on cognition, autism and brain function


at the Crnic Institute
Steven Maier, PhD
Understand the contribution of
inflammation in the brain to
cognitive deficits in Down
syndrome

Zhe Chen, PhD


Study how trisomy 21 affects
the formation of neuron axons
in the brain

Ken
aclean, Ph.D.
Ken
Maclean,
PhD
KenM
Maclean,
Ph.D.

Cognition
&&Down
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Cognition
Downsyndrom
syndrom
Test
the
impact
of the
Te
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yypp
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in
th
e
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n
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e
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R
e
sp
on
se
a
s
a
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ote
n
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l
intheUnfoldedProteinResponseas apotential
caused
by
trisomy
th
ee
ra
pp
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uu
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ttfor
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itiv
eedd
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fi21
cits
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itiv
fi
cits on

Jerry Stitzel, PhD


Investigate gene expression
changes in a key set of
neurons strongly affected
in people with Down syndrome

Kevin Jones, PhD


Investigate the impact of the
protein BDNF in the brain
pathology of Down syndrome
using mouse models

Tamim Shaikh, PhD


Research on genetic
modifiers of autism spectrum
disorders in people with
Down syndrome

cognitive deficits in Down


syndrome

All these research projects aim to identify molecular and cellular mechanisms
important for cognition.

Research on the immune system and


autoimmune conditions at the Crnic Institute
Anne-Laure Perraud, PhD
Investigates the role of the gene
TRMP22 on chromosome 21 in
innate immune dysfunction in Down
syndrome

Michael Yeager, PhD


Investigates the role of the
gene AIRE on chromosome
21 in immune dysfunction
and pulmonary hypertension

Richard Spritz, PhD


Investigates novels genes driving
autoimmunity in Down syndrome
thyroid disease, Type I diabetes,
rheumatoid arthritis and vitiligo.

Kelly Sullivan, PhD


Investigates the Interferon
molecules, potent regulators
of the immune system, in
people with Down syndrome

Kirk Hansen, PhD


Investigates the metabolic changes
that accompany inflammation and
immune dysregulation in Down
syndrome

Chris Porter, MD
Investigates changes in the
types and numbers of
different immune cells in
Down syndrome

These research projects could illuminate new ways to diagnose and treat autoimmune
disorders in people with Down syndrome.

Stem cell research at the Crnic Institute


Bradley Olwin, PhD
Investigates the role of muscle
stem cells in dysfunction of the
muscular-skeletal system in
Down syndrome

Christopher Link, PhD


Investigates changes in gene
expression caused by trisomy
21 in stem cells and neurons
derived from these cells

William
ld,
WilliamOOOld,
PhD
William
ld,Ph.D.
Ph.D.

Ganna Bilousova, PhD


Employs a new method to
generate stem cells from
individuals with Down
syndrome

Protein
Expression
&&Down
ee
Protein
Expression
Downsyndrom
syndrom
Employs
proteomics
technology
SS
tutu
dd
yygg
ee
nn
ee
ssww
ith
lte
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ddpp
rote
ininee
xp
re
ssio
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ev
ee
lop
ithaa
lte
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rote
xp
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ssion
ev
lop
to
investigate
changes
in
protein
nn
ew
th
e
ra
p
e
u
tic
stra
teg
ie
s
to
a
lle
v
ia
te
issu
e
s
w
ith
ewtherapeuticstrategies toalleviateissues with
expression
by
trisomy
nn
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uu
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ttaa
nn
dcaused
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ra
tiv
ee
pp
aa
tholog
ieie
ss 21
rod
ev
lop
m
dnn
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ra
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tholog

in stem cells

Michael Klymkowsky, PhD


Employs neuronal organoids
derived from stem cells to
investigate changes in neuron
activity caused by trisomy 21

Stem cell research is of fundamental importance, because stem cell dysfunction


could impact many of the conditions associated with Down syndrome.

Cancer and Leukemia research


at the Crnic Institute
James DeGregori, PhD
Studies problems with blood cell
production in individuals with Down
syndrome to understand the
increase risk of leukemia and
immune dysfunction

Chad Pearson, PhD


Investigates differences in how
cells with trisomy 21 sense their
environment and undergo
proliferation

Rui Yi, PhD


Investigates the effect of trisomy
21 on gene expression control in
blood cells, with a focus on
oncogenes that could drive
leukemia development

Joaqun Espinosa, PhD


Investigates novel non-toxic
therapeutic strategies
for the treatment of leukemias
showing increased incidence in
people with Down syndrome

The goal of these projects is not only to reveal why there is an increased risk of leukemia
and decreased risk of solid tumors, but also to identify and test gentler,
non-toxic therapies.

Advanced genetic and genomics research


at the Crnic Institute
Robin Dowell, PhD
Employs advanced genomics
approaches to understand how
trisomy 21 leads to changes
in gene activity across the
genome

Tom Blumenthal, PhD


Investigates changes in the
levels of thousands of proteins in
the blood of people with Down
syndrome, which could reveal
new diagnostics and
therapeutics

Aaron Johnson, PhD


Studies the way the genome of
cells with trisomy 21 is wrapped
around proteins and how this
affects gene expression

Changwei
Liu,
Ph.D.
Changwei
Liu,
PhD
Changwei
Liu,
Ph.D.

Protein
Expression
syndrom
ee
Protein
Expression&
&Down
Down
syndrom
Investigates
the
gene
USP16
SS
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dy
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ffe
ctctofofUU
SS
P16
ee
re
xp
re
ssion
on
tu
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th
ffe
P16ov
ov
re
xp
re
ssion
onaa as
on
chromosome
21,
which
lala
rg
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uu
m
bb
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rrofofoth
ee
rrce
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rote
inin
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rg
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oth
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rote
rm
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ww
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r
U
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P16
m
ay
b
e
k
ey
to
m
a
ny
p
h
e
n
oty
p
e
s
ther USP16 maybekeyto manyphenotypes

with a role in stem cell function

The goal of these projects is to gain better mechanistic understanding of how trisomy 21
affects cellular and organismal behavior at the molecular level,
with the potential for far reaching impacts in the clinic.

Future Directions
1. To continue to support strong basic science on all
aspects of Down syndrome
2. To translate key findings made by our scientists into
novel diagnostics and therapeutic applications
3. To develop alliances with government and private
agencies to develop precision medicine approaches
for Down syndrome
4. To increase our educational and outreach missions
and help disseminate the results of the latest
research among the community.