Inside Salk - June 2008 - page 6

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Inside Salk June 2008
Stem Cell Research at Salk
Juan Carlos Izpisúa Belmonte
studies the reprogramming process
inmurine and human germ stem cells, which spontaneously
transform into pluripotent embryonic stem cell-like cells when
placed in lab dishes. Since these cells don’t require any outside
help to override internal growth controls, they are less likely to start
dividing uncontrollably.
Senyon Choe
tries to identify therapeutically useful messenger
molecules involved in hESC self-renewal andmaturation to realize
the full clinical potential of stem cell therapy.
Beverly Emerson
suggests
that genes are arranged in
“neighborhoods” that are
surrounded by “fences” that
protect the activity in one
neighborhood from spilling
over into adjacent territory.
She wants to identify
the fence(s) that
border genes that are
important to
maintain stem
cells in their most
plastic state.
Fred H. Gage
and
labmembers have
developed protocols
that stimulate hESCs to
develop into neural stem
cells that can then develop
into dopamine neurons or
cholinergic motor neurons.
He will use these cells to
explore the cellular and
molecular causes for the dysfunction and
death of dopaminergic or cholinergic neurons
in Parkinson’s disease or Amyolateral
Sclerosis (ALS), respectively.
Kathy Jones
studies how transcription elongation and histone
methylation factors function to promote stem cell proliferation,
which will help future efforts to direct these cells towards specific
developmental fates.
Leanne Jones
seeks to uncover the mechanisms that regulate the
process of de-differentiation, or reprogramming, to compare these to
the mechanisms that endow stem cells with their ability to self-renew.
Reprogramming of specialized cells could provide a “reservoir” of cells
that could act to replace stem cells lost due to wounding or aging.
Jan Karlseder
is interested in how telomeres, the protective “caps”
at the end of all 46 human chromosomes, are maintained in stem cells
and how this mechanism is disabled once stem cells differentiate.
There are currently 14 principle investigators who are devoting part of
their research to stem cells at the Institute. Here are brief summaries
of what each is working to accomplish in their labs.
Kuo-Fen Lee
investigates the role of stem cells in neurodegenerative
diseases. He uses neurons derived from human or mouse embryonic and
neural stem cells to study genetic and epigenetic mechanisms underlying
the formation of synapses, the connections between nerve cells.
Satchin Panda’s
work on circadian rhythms has led him to the
question of how soon the internal circadian clock
starts ticking in developing
embryos. He will start his
search for cells ticking in
unison in stem cells.
Samuel L. Pfaff
wants to
discover the molecular signals
that coax stem cells to
develop into motor neurons,
which control our ability to
walk, talk, breath or
swallow. Over the long term,
he hopes to identify small
molecule drugs that can
help the process along.
David Schubert
uses
human neuronal stem
cells to identify both the
molecules and the
molecular pathways that
lead to the differentiation
and growth inhibition of
human stem cells. The
latter is important to
prevent embryonic stem
cells from turning cancerous, a
lethal property they all share.
Inder Verma’s
current focus
is the reprogramming of human
skin fibroblasts into hepatic
stem cells and their subsequent
differentiation into liver cells.
Lei Wang
plans to introduce
non-natural amino acids to identify unknown factors
that govern the development of stem cells into dopamine neurons.
Uncovering the mechanisms that regulate the differentiation of
embryonic stem cells into dopamine neurons may yield new drug
targets and inspire novel preventative or therapeutic strategies for
Parkinson’s disease.
Wylie Vale
and his colleague Peter Gray focus on cripto, the founding
member of a small family of vertebrate signaling proteins that function in
development. Cripto is highly expressed in hESCs, where it appears to act
as an essential cofactor for the maintenance and directed differentiation
of these cells.
Senyon Choe
Lei Wang
Samuel L. Pfaff
Beverly Emerson
Fred H. Gage
Leanne Jones
Jan Karlseder
Wylie Vale
Juan Carlos Izpisúa Belmonte
Kathy Jones
David Schubert
Kuo-Fen Lee
Satchin Panda
Inder Verma
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