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
ee
Anesthesia
Downsyndrom
syndrom
Investigates
the
impact
of the
Te
st
th
e
id
e
a
th
a
t
ov
e
re
x
p
re
ssion
of
a
k
ey
g
e
n
ee
TeRCAN1
st theideathatgene
overexpre
ssionchromosome
of akeygen
on
on
ch
rom
osom
e
21,
p
rom
ote
s
th
e
d
ev
e
lop
m
e
n
ttofof
onchromosome21, promotes thedevelopmen
AA
lzh
ee
im
ein
rs
ise
aa
se
-re
lala
tete
ddnn
ee
uu
rop
aa
th
ology
21
development
lzh
im
e
rsdthe
d
ise
se
-re
rop
th
ologyof

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
ee cellular
Cognition
Downsyndrom
syndrom
Test
the
impact
of the
Te
ststaahh
igig
hh
lylysp
ee
cifi
c inhh
ibib
itor
ee
yypp
rote
ininaa
ctiv
ee
Te
sp
cifi
itorofofaakk
rote
ctiv
response
tocininunfolded
proteins
in
th
e
U
n
fold
e
d
Prote
R
e
sp
on
se
a
s
a
p
ote
n
tia
l
intheUnfoldedProteinResponseas apotential
caused
by
trisomy
th
ee
ra
pp
ee
uu
tic
rg
ee
ttfor
cog
nn
itiv
eedd
ee
fi21
cits
th
ra
tictata
rg
for
cog
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
re
ddpp
rote
ininee
xp
re
ssio
ntotodd
ev
ee
lop
ithaa
lte
re
rote
xp
re
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
ee
uu
rod
ev
ee
lop
m
ee
nn
ttaa
nn
dcaused
ee
uu
rod
ee
gg
ee
nn
ee
ra
tiv
ee
pp
aa
tholog
ieie
ss 21
rod
ev
lop
m
dnn
rod
ra
tiv
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
tu
dy
eeee
ffe
ctctofofUU
SS
P16
ee
re
xp
re
ssion
on
tu
dyth
th
ffe
P16ov
ov
re
xp
re
ssion
onaa as
on
chromosome
21,
which
lala
rg
eenn
uu
m
bb
ee
rrofofoth
ee
rrce
llu
lala
rrpp
rote
inin
sstotodd
ee
tete
rm
inin
ee
rg
m
oth
ce
llu
rote
rm
known
epigenetic
regulator
ww
hh
ee
th
e
r
U
S
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.