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.
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
CULPEPER BIOMEDICAL PILOT GRANTS: PREVIOUS GRANTEES
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