Charles E. Culpeper
Biomedical Pilot Initiative
CULPEPER PILOT GRANT
PROPOSAL GUIDELINES
CULPEPER BIOMEDICAL PILOT GRANTS: PREVIOUS GRANTEES
The Goldman Philanthropic Partnerships
Charles E. Culpeper
Biomedical Pilot Initiative Grants
The Culpeper Biomedical Pilot Initiative Grants encourages
the investigation of novel ideas of interest to donors of
Goldman Philanthropic Partnerships to cure diseases,
particularly through genetics, bio-engineering, and
pharmacology. Grants of up to $25,000 will be made on a
one-time basis. These Pilot Grants explore new and even
untested hypotheses. Applicants include young investigators
seeking to establish independent directions or established
investigators pursuing new directions. These Pilot Grants
should be viewed as "venture capital" investments that lead
to greater funding opportunities through traditional
sources. These Pilot Grants are part of our partnership
with the Rockefeller Brothers Fund, providing three dollars
of funding for each dollar of GPP donor funds.
{Click on
Researcher's Name For More Information}
Saving the World from
SARS
SARS is
a deadly human illness that first appeared in 2002 in China
and has spread to more than 30 countries. SARS is caused by
a coronavirus, the genome of which has been sequenced.
Knowledge of the SARS genome makes it possible to develop an
early detection test for SARS, preventing the global spread
of SARS. This study will develop this innovative test for
SARS, which would hook a molecule that glows in the dark to
a protein that would attach a specific spot on the SARS
gene. An infected patient’s blood sample would immediately
glow, simplifying and speeding up detection at a very low
cost.
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Making the Microscope
Work Harder
This
project will develop a new highly sensitive microscopy for
the imaging of molecules using vibrational imaging.
Traditional microscopy suffers from noticeable background
noise that limits its sensitivity when looking at the
smallest molecules. Vibrational imaging records
simultaneous pictures of the molecules and superimposes them
on each other eliminating the background noise. This imaging
technique will “clearly” bring microscopy to a new level.
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Gregory Crawford, PhD, Brown
University
The Picture of Health
Anemia, the lack of healthy red blood
cells, has long been viewed as the innocent bystander of
disease; however there is compounding evidence indicating
that anemia is a significant free-standing health issue that
is severely under diagnosed and rarely managed properly in
patients with life altering and chronic diseases. Just as
patients can monitor their own heart rate, blood pressure,
and blood sugar, enabling patients to measure their own
anemia by monitoring their red blood cells at home will
empower patients and improve their quality of life. This
proposal will create a device that will take a photo of the
lining of the lower eyelid using a small camera. A computer
program will compare the red color of the photo with a
standard to determine in real time how many red cells are
present to determine the patient’s anemia. The device could
provide accuracy similar to the current lab test when the
physician draws blood from the patient. Dr. Crawford and his
research team envision the final device to be small,
inexpensive and integrated onto a PDA (personal digital
assistant) device or a cell phone so that it can be integral
to home health care situations in helping people better
manage the consequences of life altering diseases.
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Benoit de Crombrugghe, MD, M.D. Anderson Cancer Center
Finding a Way to Cure Colorectal Cancer
The walls of gut are folded
into numerous valleys and peaks that increase surface area
for absorbing nutrients. The surface cells are
consistently renewed from stem cells located toward the
bottom of the valleys. In most colorectal cancer, a
protein becomes abnormally active in these stem cells and
they multiply out of control. This proposal will
discover whether control of this protein could halt
colorectal cancers.
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Theo Kofidis, MD, Stanford
University
A New Way to Heal a Broken Heart
The human heart has a limited capacity
to repair itself except by scar formation. Scar formation
healing results in loss of pumping capacity and often leads
to heart failure. An increasing body of evidence suggests
that certain types of stem cells may have the capacity to
restore injured heart muscle and function when grafted into
the area of injury. The optimal type of cell graft for
heart muscle restoration must:
1. Provide structural support for the
injured area
2. Be strong enough to survive in the
stressful heart environment
3. Induce new blood vessels to grow
This innovative research project will
first create a bio-compatible foam scaffold onto which
embryonic heart stem cells will be grafted. In the lab the
cells will grow on the scaffold forming new heart tissue.
Next, the researchers will implant the scaffold and graft
into the abdomen of the animal that will later receive the
graft to allow blood vessels to grow into the graft and
provide blood flow to keep the graft alive. This graft is
then removed from the abdomen and transplanted onto the
heart. After the surgery the graft is monitored using
chemicals which give off detectable light energy if the
graft is functioning. This radically new idea for healing a
broken heat could supplement or replace Coronary Artery
Bypass Surgery and Cardiac Transplantation.
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Stephen Kron, MD, PhD, University of
Chicago
The Knock-Out Punch for Cancer Cell
Chemotherapy
Most cancer chemotherapy works by
damaging the DNA of cancer cells. When these cancer cells
divide, the damaged DNA causes the cell to die. All cells,
especially cancer cells, have the ability to repair the
damaged DNA before the cell divides. If the DNA is repaired
before the cell divides, the cancer cell will not die.
Dr. Kron and his colleagues have
discovered a key molecule in cancer cells, HA2X, that is
required to rapidly repair DNA damage. This study will test
over 20,000 small molecules that can block the effectiveness
of HA2X. A molecule that can block HA2X will theoretically
deliver the knock-out punch that would allow chemotherapy to
kill all cancer cells, especially in cancers that have
spread around the body. Dr. Kron’s breakthrough research
could have a significant impact on survival and quality of
life of all cancer patients.
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Building the Six-Million Dollar “Lab” Man
Drug development must
identify compounds that are toxic to healthy human cells.
Early toxicity identification reduces the danger to patients
and cost to the pharmaceutical companies. Lab studies do
not always predict how the drug will affect cells when it is
given to animals or humans in clinical studies because test
cells are not in the actual “body environment”. This
project will create a three dimensional structure in the lab
with test cells in contact with each other, mimicking the
“body environment”. This tissue-like environment should
more accurately predict toxicity of drugs when they are
actually given to humans.
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Michael Marletta, PhD, University of
California, Berkeley
A New Understanding of How Blood Vessels Work
Dilation of the blood vessels in the
heart and other tissues is controlled by a reaction inside
cells that gives off the chemical nitric oxide (NO). NO
causes the muscle cells of the blood vessel walls to relax
so the vessel can expand. Dr. Marletta and co-workers
recently discovered that the accepted mechanism for how NO
causes this relaxation is fundamentally incorrect.
Determining the details of these new findings will lead to a
better understanding of normal heart and blood vessel
function, and to new approaches for treating heart disease
and other cardiovascular ailments. This proposal will
explore the action of NO on a specific enzyme target in the
cardiovascular system. Based on current data, the consensus
opinion is that nitric oxide directly activates the enzyme,
and that another molecule deactivate the enzyme. Pilot data
suggests that a novel feature of the enzyme itself controls
both activation and rapid deactivation. Confirming these
results could provide novel treatments of cardiovascular
disease through manipulation of the target enzyme.
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Malcolm Potts, PhD, University of
California, Berkeley
When Medicine Hands you Lemons, Make
HIV Lemonade
Sexual transmission of HIV and
other sexually transmitted diseases (STDs) continue at
epidemic pace globally. HIV researchers believe that
microbicides, chemicals that can kill bacteria and viruses,
can reduce the transmission of HIV and other STD pathogens
when applied vaginally. Current academic and
pharmaceutical research is focusing on the lengthy and
expensive process of developing new microbicide drugs
Women around the world have used
diluted lemon or lime juice as a microbicide in many
countries. Lemons and limes are inexpensive and locally
available in nearly every country. In lab studies,
lemon/lime juice kills HIV on contact and has been proven
safe for use in the vagina’s of monkeys.
If lemon juice is effective in
reducing HIV transmission in humans, the world will have and
inexpensive and life saving prevention for a catastrophic
disease, and a benchmark of safety and effectiveness for
testing futures microbicides. Dr. Potts and his team will
test whether lemon juice is safe when self-applied to a
woman’s vagina.
If this test proves that dilute lemon
juice is safe, a human clinical trial will begin to test
whether lemon juice does reduce HIV infections and other
STD’s. Dr. Potts’ research has the potential to introduce a
safe, effective, available, and inexpensive method years
before a commercial microbicide becomes available.
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Peter Rowley, MD, University of
Rochester Medical Center
Stopping Multiple Myeloma Before the
Fork in the Road
Multiple myeloma is an
incurable blood-bone cancer. The disease is caused by two
or more defective genes. One of the reasons it is so hard
to defeat is that these multiple gene defects create a
variety of pathways the disease uses to keep growing. There
are many therapies that can kill myeloma cells, but other
myeloma cells just keep growing using alternative pathways,
and eventually the patient succumbs to the disease.
Dr. Rowley and his team have developed
a new technology that can stop more than one defective gene
at the same time. His team has already shown that this
therapy, a gene inhibitor called peptide nucleic acid (PNA),
can block one defective gene in multiple myeloma cells.
This new project will create a PNA to
the other major gene defects, so that myeloma cells will be
killed without having an alternative path around the
therapy. If this project is successful, there is hope that
this incurable disease will soon be conquered, and that
other resistant, incurable cancers can also benefit from
this powerful therapy.
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Yanhong Shi, PhD, City of Hope:
Beckman Research Institute
What Can Stem Cells Teach us about
Curing Cancer?
Stem cells have the unique abilities to
self-renew and to change into other kinds of cells. Cancer
cells have the same characteristics. Dr. Shi and her
colleagues believe that many of the pathways that help stem
cells self-renew and change are the same pathways used by
cancer cells, especially brain tumor cells.
Dr. Shi has discovered a compound
called TLX which is critical to the self-renewal process in
adult brain stem cells. When cells don’t have TLX, they
can’t grow. If you give these cells TLX, they will begin to
multiply. These discoveries have created this research,
during which the Dr. Shi team will determine whether brain
tumor cells use TLX to help them grow and multiply.
If they team finds TLX is required for
brain tumor growth, they will find the genes that TLX
affects in both brain stem cells and brain tumor cells.
Comparison of these two cell types will allow researchers
to create anti-tumor therapies that can attack the TLX
sensitive genes in brain tumor cells, creating treatments
for these devastating, incurable cancers, and for other
brain related diseases.
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Randy Sigle, PhD, Fred Hutchinson
Cancer Research Center
As Smooth as Silk and Then Some…
The cells of the human body are held
together by something we call extra-cellular matrix.
Extra-cellular matrix is a complex of proteins and other
components that not only provide structure for the body, but
also provide a way for signals to get from one cell to
another. When the extra-cellular matrix breaks down in a
wound, or is pushed out of the way when a tumor takes over,
the body no longer functions normally.
The search is on to create a synthetic
extra-cellular matrix that we envision can be used for four
purposes: research on how changes in the extra-cellular
matrix affect the body; replacing damaged extra-cellular
matrix in wound situations; as a therapy when drugs are
incorporated into the synthetic extra-cellular matrix before
it is placed into the body; and as a scaffold for designing
artificial body parts.
Silk from silkworms is a compelling
candidate for this synthetic extra-cellular matrix. It is
abundant, nearly pure, and can be made in both water soluble
and non-water soluble forms. Dr. Sigle and his team will
begin to determine whether or not the biological activities
of the human extra-cellular matrix can be incorporated into
silk. If their hypotheses are correct, this research could
lead to the development of new therapies for wound healing
and cancer, as well as the initiation of a new paradigm for
tissue engineering.
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Gabriel Silva, PhD, University of
California, San Diego
It’s a Blood Cell, It’s A Stem
Cell, It’s Supercell
More than 50 million people worldwide
are going blind because the light receptor cells in their
eyes have broken down. There are few treatments that can
slow these diseases, and none that can cure them. The most
promising research is centering on replacing the damaged
light receptors cells. Researchers have found certain blood
cells found in the bone marrow can be transformed into light
receptor cells. These blood cells are called adult stem
cells because they can turn into a wide variety of cells in
the body. Other researchers have made some of these blood
stem cells look like light receptor cells.
However, while they look like light
receptor cells, they don’t function like light receptor
cells. Dr. Silva and his team have hypothesized two
breakthroughs that may lead them to rapidly develop new
light receptor cells that can be transplanted into the eye
to restore the vision that these patients have lost.
The first breakthrough that Dr. Silva
and his team believe is necessary is to provide just the
right mix of chemical and other signals that natural light
receptor cells would receive as they are maturing.
More importantly, a second breakthrough
is needed, to create a special three dimensional nano-environment
on which these cells can grow. This three dimensional
structure mimics the structure of the retina where light
receptor cells normally grow. In the end, Dr. Silva and his
team are trying to re-create the exact environment in which
normal light receptor cells grow, so these stem cells can
grow into functional light receptor cells.
If Dr. Silva and his team are correct,
these new “Supercells” will be able to save the sight that
so many people continue to lose.
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Gultekin
Tamguney, PhD, University of California, San Francisco
A Cure for Mad Cow Disease
Mad Cow Disease is a rare, fatal
disorder in humans with no current treatment or cure. The
disease is caused by an abnormally folded piece of cellular
protein called a prion that accumulates in the brain.
Research has shown that antibodies, a special molecule
produced by the body’s immune system that recognize and help
fight infectious agents, can bind to the prion to “cure” a
prion infection in a cell culture model. Until recently
antibody therapy for human prion diseases did not seem
feasible since prion-binding antibodies could not cross the
blood-brain barrier. The aim of this proposal is to link
prion-binding antibodies with a molecule that will cross the
blood brain barrier, like hooking a caboose (the prion-binding
antibody) to an engine (the molecule that will cross into
the brain) so the caboose can get to where it needs to go.
The “engine” molecule will release the antibody once it is
inside the brain, so the antibody can bind to and destroy
the prions. This type of treatment could either provide a
vaccine that would protect a person from prion disease or a
treatment that would cure prion disease after infection.
Further, a successful outcome for this project could open
the door to novel treatment strategies for similar brain
diseases associated with the accumulation of misfolded
proteins such as Alzheimer’s and Huntington’s Disease.
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David Teachey, MD, University
of Pennsylvania School of Medicine
Translating Knowledge
from One Disease to Cure Another
Normally,
the body creates new cells and eliminates worn out cells in
a process called apoptosis, or cell death. In ALPS
(Autoimmune Lymphoproliferative Syndrome), the body
accumulates old white blood cells, which damage organs and
red blood cells causing anemia, fatigue, internal bleeding,
and infection. The drug Rapamycin prevents organ transplant
rejection and is also effective in treating white blood cell
cancers, through apoptosis. Rapamycin might be effective in
treating ALPS. This study will first test the drug in a
mouse model of ALPS. If it works, the drug will be tested
on ALPS patients, who have no other effective form of
therapy and usually do not survive the disease.
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Joseph
Vinetz, MD,
University of California, San Diego
Halting Malaria in its Tracks
Malaria is one of the world’s most prevalent diseases,
killing 1-3 million people (mostly children) annually.
Mosquitoes spread malaria to humans. This project will use
genomics to determine how malaria moves from humans to
mosquitoes and back, testing a breakthrough to keep the
malaria parasite from reproducing in the mosquito, breaking
the transmission cycle. After understanding this
mechanism, novel methods of interrupting the transmission of
malaria can be created.
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Steven J.
Weintraub, MD,
Washington University School of Medicine
Eliminating Resistance to Chemotherapy
Chemotherapy
agents cure few types of cancer and have significant side
effects. These agents have many effects on cancer cells,
and little is known about which effects cause cancer cell
death. Many drugs kill cancer cells by modifying cell
proteins that cause cell death. When the modification is
blocked, the cells become resistant to chemotherapy.
Recently, it was discovered that compounds found in many
cancers block the chemotherapy protein changes. Cancers
with these compounds are quite resistant to chemotherapy.
Understanding the mechanism by which these cancer compounds
block chemotherapy could lead to an improvement in the
treatment of a wide variety of cancers.
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CULPEPER BIOMEDICAL PILOT GRANTS: PREVIOUS GRANTEES
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