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A
new palliative care program
has been established at both Emory and Emory Crawford Long hospitals,
focusing on alleviating suffering and improving quality of life for patients
who have a serious illness. Palliative care not only relieves both the
physical and non-physical suffering that accompanies serious illnesses
but also addresses mental health and spiritual needs.
Staffed by internal medicine physicians
and co-directed by hospitalists Stephanie Grossman and Melissa Mahoney,
who are board certified in palliative care, the program is part of a rapidly
growing trend in health care. Not to be confused with hospice care, palliative
care is appropriate for patients in any stage of illness, not just for
those approaching the end of life. The team includes physicians, nurses,
social workers, chaplains, and pharmacists.
Grady Hospital also has a palliative care
clinic for cancer patients, funded by a $200,000 grant from the Lance
Armstrong Foundation.
Mutant
plants to the rescue
Global
warming may have met its match. Emory researchers have discovered a mutant
enzyme that could enable plants to use and convert carbon dioxide to sugar
(3-phospho-glycolate) more quickly, effectively removing more greenhouse
gases from the atmosphere.
During photosynthesis, plants and some bacteria
convert sunlight and carbon dioxide into usable chemical energy—a
process that relies on an enzyme called RuBisCO. While RuBisCO is the
most abundant enzyme in the world, it is one of the least efficient.
“All life pretty much depends on the
function of this enzyme,” says biochemist Ichiro Matsumura. “It
actually has had billions of years to improve but remains about a thousand
times slower than most other enzymes. Plants have to make tons of it just
to stay alive.”
For decades, scientists have struggled to
engineer a variant of the enzyme that would more quickly convert carbon
dioxide. For the Emory study, Matsumura and colleagues used a process
called directed evolution, which involved mutating genes, inserting them
into bacteria (in this case E. coli), and screening for the fastest and
most efficient enzymes produced by the mutant genes.
Matsumura’s team then added genes
encoding RuBisCO to E. coli to enable the bacteria to change carbon dioxide
into consumable energy. They then added mutated RuBisCO gene to the modified
E. coli. The mutations of the fastest-growing strains caused a 500% increase
in RuBisCO expression.
“We are excited because such large
changes could potentially lead to faster plant growth,” says Matsumura.
More plants using and converting carbon dioxide more quickly means less
pollution and greenhouse gases.
Gleevec
for smallpox?
The hallmark
anti-cancer drug Gleevec may be effective in controlling smallpox infections
or treating the complications caused by smallpox vaccines. Emory scientists
administered Gleevec to mice and infected them with lethal doses of the
poxvirus used to vaccinate against smallpox. They found that the drug
reduced dissemination of the virus and the mice survived. The Emory investigators,
led by pathology researcher Daniel Kalman, tested Gleevec against poxviruses
after their discoveries about how the viruses interact with host cells
on a molecular level. The virus particles become encased in an envelope
that helps them evade the immune system, then travel to the cell’s
surface, where the enveloped viruses hijack host-cell proteins, which
allow them to detach and spread to other cells.
Kalman and colleagues speculated that Gleevec
might be effective against poxvirus without eliciting drug resistance
because it inhibits the host cell molecule, rather than the viral molecule.
“It would be hard for the virus to overcome blockade of a host cell
factor because it would have to completely change its virulence program,”
says Kalman. He believes the concept of using anti-cancer drugs to treat
microbial infections may prove to be more generally applicable. “Many
pathogens use host molecules as part of their pathogenic program,”
he says.
Nanotechnology
funds for cancer
The
National Cancer Institute (NCI) has selected Emory and Georgia Tech as
one of seven National Centers of Cancer Nanotechnology Excellence. The
Emory-Georgia Tech Nanotechnology Center for Personalized and Predictive
Oncology will function as a discovery accelerator to integrate nanotechnology
into personalized cancer treatments and early detection.
With the new designation, Emory and Georgia
Tech now have one of the largest federally funded programs in the United
States in this arena. The NCI grant is expected to reach $19 to $20 million
over a five-year period.
Nanotechnology is research and technology
at the atomic, molecular, or macromolecular levels, where particles are
measured with a nanometer equivalent to one-billionth of a meter (or 100,000
times smaller than the width of a single strand of human hair). It offers
promise for earlier cancer detection, personalized diagnostics for targeted
treatment, and creation of new drugs for metastatic cancers.
“Nanotechnology will eventually apply
to all cancers,” says Bill Todd, CEO of the Georgia Cancer Coaltion
(GCC). “However, this grant is focusing on breast and prostate cancers,
which represent compelling challenges in cancer research.”
The center’s director, Shuming Nie,
an Emory faculty member and GCC Scholar, is leading collaborative research
to develop several kinds of nanoparticle probes, including quantum dots,
which are luminescent nanoparticles that can be chemically bound to biologic
particles such as antibodies or proteins. Such dots therefore can act
as markers to study protein interactions in live cells or to detect diseased
cells.
Jonathan Simons, outgoing director of the
Winship Cancer Institute, is co-principal investigator of the grant.
This NIH support came on the heels of other
major NIH awards, including one for $11.5 million, again to Emory and
Georgia Tech, to Gang Bao and colleagues, who are using nanostructured
probes to detect cardiovascular plaques.
Treating
(and preventing) injuries in Mozambique
If
a motorist is hurt in a car crash in Mozambique, it is likely that the
first person to tend to his or her injuries will be a bystander or a taxi
cab driver.
EMS systems like those that exist in the United
States to aid accident victims are “far beyond the reach of most
low-income countries,” says Scott Sasser, assistant professor of
emergency medicine. “What they need are simple and sustainable strategies
for improving prehospital care.”
While much of the attention in global health
assistance is geared toward disease prevention and treatment, WHO estimates
that 5 million people worldwide die of injuries each year—largely
in developing nations.
Sasser, emergency medicine physician David Wright,
and surgeon Jana MacLeod have received a five-year, $675,000 grant from
the Fogarty International Center of the NIH to establish an injury control
program in Mozambique.
“When I did ward rounds at the Central
Hospital Maputo, I discovered that 60% of the patients we saw that morning
were admitted with an injury-related diagnosis,” says MacLeod. “For
the general surgeon in such an environment, up-to-date knowledge about
appropriate evidence-based trauma care is essential. Also, injury prevention
will have a significant impact because of the relative volumes of injury,
compared with other types of admissions to the Maputo hospital.”
Mozambique was selected as the site of the
program—which Sasser hopes will become a model for other African
nations—because, according to WHO, its government was prepared to
support efforts to reduce its “injury epidemic.” Through a
partnership between Emory and Mozambique’s University Eduardo Mondlane,
academic and clinical core medical faculty in Mozambique will be trained
in the principles of public health, research methods, ethical principles,
and safety promotion.
Sasser also is working with WHO and the
City Council of Maputo to improve prehospital care within the city. His
efforts are based on the recently published WHO monograph, “Prehospital
Trauma Care Systems,” of which he was lead editor.
“Instead of buying 50 new ambulances
that can’t be maintained or providing advanced training that existing
technology can’t support, we look at what can be done,” says
Sasser, “such as teaching basic first aid to interested community
members.”
The Fogarty grant will support the training
of 10 fellows from Mozambique in trauma and injury control. The fellows,
mostly clinicians, will spend their first year in Africa completing coursework,
followed by stints at Emory’s Rollins School of Public Health and
the University of South Africa, returning to Mozambique to put methods
into practice. —Mary
Loftus
Bernstein wins Novartis Prize
Emory
pathologist Kenneth Bernstein was the 2005 co-recipient of the Novartis
Prize from the American Heart Association, marking the second consecutive
year that an Emory faculty member has won the award. In 2004, the award,
which honors contributors to advancing knowledge of hypertension, vascular
disease, and cardiovascular disease, went to Emory cardiologist David
Harrison.
Bernstein and his colleagues have been responsible for a number of important
discoveries about the link between the kidneys, blood pressure, and cardiovascular
function, including cloning and characterizing the gene for the receptor
for angiotensin II, the central component of the process of blood pressure
control.
New blood vessels in
the heart, thanks to gene transfer
Emory Crawford Long Hospital is one of 32 sites participating
in a national study of experimental gene transfer designed to stimulate
new blood vessel growth in the heart. Researchers hope this new treatment
will restore blood flow to ischemic areas of the heart in patients with
severe angina due to coronary artery disease and who have few or no remaining
treatment options.
The procedure involves injecting a special
gene directly into the heart muscle in six places through a specialized
catheter. The goal is for the gene to provide the heart with instructions
to grow new blood vessels.
The results of earlier phase 1 and 2 trials
have been encouraging, according to cardiologist Henry Liberman, who leads
the study.
A
big breakthrough in curing diabetes, with help of pigs and monkeys
Islet
cell xenotransplantation presents a promising near-term solution to the
problem of critically low islet cell supply for people with type 1 diabetes.
Researchers from the Emory Transplant Center have transplanted insulin-producing
neonatal porcine islet cells harvested by University of Alberta (Canada)
researchers into diabetic rhesus macaque monkeys, restoring the monkeys’
glucose control and resulting in sustained insulin independence.
Islet cell transplantation has successfully
reversed type 1 diabetes in humans, but the availability of islet cells
limits use of this procedure in reaching more than 1 million Americans
with the disease. Each year, only 3,000 to 4,000 donor pancreases are
available, and each can produce enough islet cells for, at most, only
one transplant. “We must find new donor sources to allow large-scale
application of islet cell transplantation in humans,” says Emory
transplant researcher Chris Larsen.
Published in February in Nature Medicine,
this research also examines the effectiveness of a costimulation blockade-based
regimen developed by Larsen and his colleague Thomas Pearson, which has
fewer toxic side effects than currently used immunosuppressive regimens.
Belatacept is a key ingredient in the costimulation
blockade that selectively blocks the second of two cell signals the body
needs to trigger an immune response. This regimen is less complex than
the immunosuppressant compounds used in previous research, and its simplicity
will make it more applicable in clinical use.
In addition, Emory researchers addressed
concerns of the possibility of cross-species disease transmission as a
result of xenotransplantation. After extensive testing, they found no
evidence of transmission of porcine endogenous retroviruses between the
porcine cells and the transplant animals. The use of nonhuman primates
was critical for testing cross-species viral transmission due to their
close genetic link to humans, according to Larsen.
The next step is to prove porcine islet cells
can be a source for human transplantation and to verify the safety of
the transplant procedures, a process researchers hope to begin in the
next three to five years.
Clues about ketogenic
diet and seizures
Physicians have long prescribed a high-fat, calorie-restricted
ketogenic diet to prevent childhood epileptic seizures that are unresponsive
to drugs, but until now no one has understood why the diet works. New
studies at Emory show that the diet alters the expression of genes involved
in energy metabolism in the brain, which in turn helps stabilize the function
of neurons exposed to the challenges of epileptic seizures.
To identify which genes might be involved
in this process, the Emory research team, led by pharmacology chair Raymond
Dingledine, used microarray gene chips to examine changes in gene expression
for more than 7,000 rat genes. They focused on the hippocampus, finding
more than 500 genes that correlated with treatment with the ketogenic
diet, including genes involved in energy metabolism.
To test whether energy reserves in hippocampal
neurons were enhanced with the diet, they counted the number of mitochondria
within cells, using electron microscopy. They found that ketogenic diet
treatment significantly increased the number of mitochondria per unit
area in the hippocampus and concluded that the diet enhances energy production
in the hippocampus and may lead to improved neuronal stability.
The researchers also tested whether brain
tissue affected by the diet would be better able to withstand metabolic
changes associated with seizures, such as lowered glucose levels, because
of enhanced energy reserves. They found that synaptic communication in
rats on the ketogenic diet was more resistant to low glucose levels.
This new knowledge could lead to the development
of more effective drug treatments for epilepsy and brain damage. The researchers
also believe that the ketogenic diet should be studied as a possible treatment
for neurodegenerative disorders such as Alzheimer’s or Parkinson’s
diseases.
Cystic fibrosis has
an older face
The median
age of cystic fibrosis patients has risen from 14 in 1969 to 35 in 2004,
with almost 40% of today’s patients already 18 or older. The Cystic
Fibrosis Adult Program at Emory is the only one in Atlanta geared to the
needs of adults living with the disease, which affects 30,000 people in
the United States. The program is comprehensive, assembling pulmonologists,
gastroenterologists, nutritionists, respiratory therapists, and others
to serve more than 140 adults—the oldest of which is now in his
mid-60s. A multi-pronged translational research program including studies
on antioxidant production and lung inflammation and the role of pollution
and ultraviolet light exposure helps researchers test multiple hypotheses
simultaneously to further increase the life span of those with cystic
fibrosis, says Arlene Stecenko, who directs the center and its research.
Center faculty also are examining the potential for gene therapy and determining
the molecular makeup of some 900 mutations of the cystic fibrosis gene
and its functions.
On the rebound:
more clues to bone loss
Osteoporosis may be caused by a “thymic rebound”
resulting from estrogen deficiency and increased production of the protein
IL-7, according to research led by Garland Herndon Professor of Medicine
Robert Pacifici and published in the Nov. 2 online edition of Proceedings
of the National Academy of Sciences.
The research is based on earlier findings
suggesting a link between estrogen deficiency and an increase in the number
and activity of T cells. Increased T cell activity also leads to increased
levels of TNF, which helps ward off infections but causes bone loss.
The Emory team discovered a cause for the
increase in T cells and TNF production: reactivation of the thymus, which
is where T cells finish developing after differentiating from stem cells
in the bone marrow. The findings suggest a direct link between the functioning
of the thymus and bone loss.
Scientists have long believed that the thymus
is inactive after childhood, but Pacifici and his colleagues found otherwise.
Their data in mouse models (and there is similar evidence in humans, says
Pacifici) showed that with estrogen deficiency the thymus surprisingly
comes back to life and starts pumping out new T cells.
Estrogen deficiency sets off a chain reaction,
he explains, triggering increased production of IL-7, which causes production
of new bone marrow stem cells and reactivates the thymus. “This
thymic rebound results in a profusion of T cells, which in turn leads
to increased generation of TNF.”
While a thymic rebound may be helpful to
people dealing with immunodeficiency diseases such as AIDS, the purpose
in estrogen deficiency remains unclear. “There are times for the
thymus to come back to life and make new T cells,” Pacifici says.
“In estrogen deficiency, there is no clear helpful reason for that.
It’s an unexpected phenomenon.”
More than happiness:
the science behind satisfaction
Psychiatrist Gregory Berns is curious about how the human brain
works. In his laboratory at Emory, he uses imaging techniques such as
MRI to study how the brain functions during tasks that have a level of
uncertainty, novelty, and even decision-making. His curiosity and research
have led him to develop a theory about how people are motivated, which
he explores in a new book, Satisfaction: The Science of Finding True
Fulfillment.
The book examines the drive that motivates
people, from running a marathon to maintaining novelty in a relationship.
“There were many activities that seemed mysterious to me, the culinary
magic of great cooking, Aha! moments of intellectual stimulation, the
fascination of self-inflicted pain, the challenge of a crossword puzzle,”
Berns says. “The satisfaction of those pursuits appeared to derive
from doing something novel and tapped directly into the motivation centers
of the brain.
“Everything I have encountered inside
the research lab and out in the world suggests that satisfaction is not
the same as either pleasure or happiness, and searching for happiness
will not necessarily lead to satisfaction.”
Why response to therapy
varies in rheumatoid arthritis
New
findings by Emory researchers—that growth factors in the immune
system have both pro- and anti-inflammatory roles in rheumatoid arthritis—help
explain why some patients respond to current therapy for this disease
and others don’t.
Rheumatologists Cornelia Weyand and Jorg
Goronzy have helped delineate three different subtypes of RA over the
past 10 years (diffuse RA, germinal center synovitis, and aggregate synovitis)
and say that rheumatologists need to develop diagnostic tools to discern
differences among patients to help determine appropriate therapy. Current
therapies targeting inflammatory growth factors are applied universally
to all RA patients, without accounting for differences in disease, even
though not all RA patients respond well to these therapies.
In recent work, Weyand and Goronzy used
a humanized mouse model to study growth factors known for helping B cells
survive and differentiate. Two of these proteins, known as APRIL and BlyS,
are targets of new experimental drugs currently in early-phase clinical
trials.
The researchers implanted human tissue from
RA patients with the three types of disease into mice engineered to lack
a natural immune response. They then treated the mice with a soluble receptor
targeted to remove APRIL and BlyS from the affected tissue.
They found that in the mice carrying tissue
from patients with germinal center synovitis, the inflammatory process
was halted. In mice carrying tissue from patients with the other two types
of RA, however, the opposite happened, and the growth factors and inflammation
increased.
“This is a very surprising result,”
says Weyand. “We found that these two factors do more than just
support the growth and differentiation of B cells. They also can bind
to T cells. In the tissues that had worsening of the disease, we found
T cells binding APRIL and BLyS, telling us that these T cells had actually
been suppressing the disease.”
Mental
health for the homeless
Can intensive
case management, education, and coordination of services for homeless
people improve their mental health and keep them off the streets? That’s
the question Emory psychiatrist Raymond Kotwicki is exploring with a $250,000
grant from United Way of Atlanta. His Education and Community Services
Engagement Linkage (ECSEL) study will compare two similar groups of patients
who are randomized to either a usual care group or an experimental group.
Half of the participants will receive the same care they currently get
at Grady Memorial Hospital, while the other half will receive enhanced
levels of case management and services.
“Those receiving care through ECSEL are some of the leading users
of expensive tertiary care such as psychiatric emergency services and
hospitals,” says Kotwicki. “We hypothesize that the life support
and case management services provided to homeless people will cost taxpayers
less than safety net health services and jail.”
Trials
against cancer
Emory’s
Winship Cancer Institute is conducting some 115 clinicals trials, including
a number initiated at Winship.
Winship was the first cancer facility in
the country, for example, to open a trial of a new combination of chemopreventive
drugs for the oral cavity and larynx in former smokers. Researchers are
using a combination of erlotinib and celecoxib to block epidermal growth
factor receptor (EGFR) mediated signaling and to inhibit cyclooxygenase-2
mediated pathways.
Erlotinib blocks EGFR tyrosine kinase protein
messaging, which tells cancer cells to grow and divide, and celecoxib
is an anti-inflammatory that reduces cell formation, blood vessel formation,
and metastases. Individually, the drugs have been found to be effective
chemopreventive agents. This study will evaluate the safety and effectiveness
of the two drugs in combination.
Winship is the only cancer facility in Georgia
offering a phase 2 trial for transitional cell carcinoma, a common form
of bladder cancer, testing the efficacy of the investigational drug Vinflunine.
Previous studies have shown that the drug exhibits anti-tumor activity
by inhibiting cell division. The purpose of the trial is to assess whether
it will shrink tumors or slow their growth in patients with advanced bladder
cancer that is worsening despite chemotherapy.
Winship is one of only two cancer research
facilities in the country to conduct a procedure to determine how much
chemotherapy actually reaches certain kinds of brain tumors. In the procedure,
a microdialysis catheter is inserted directly into the patient’s
brain tumor. The patient then receives an intravenous infusion of methotrexate.
Researchers use the catheter to remove fluid directly from the tumor.
They hope to determine exactly how much of the drug reaches the tumor
by removing fluid for 24 hours after the chemotherapy is delivered. Patients
in the study have recurrent, malignant, high-grade gliomas, one of the
most difficult types of brain tumors to treat.
Finally, Winship researchers participating
in a phase 3 multicenter, international study found that bortezomib, one
of a new class of drugs known as proteosome inhibitors, showed promise
against multiple myeloma, as reported in the New England Journal of
Medicine last June. Proteosome inhibitors are designed to specifically
inhibit the proteasome, an enzyme complex in the cell responsible for
breaking down a variety of proteins, including many that regulate cell
division. Unlike traditional chemotherapy drugs, this drug works at the
molecular level to interrupt the mechanism that myeloma cells use to reproduce
themselves. It also has less impact on normal cells, says Winship hematologist
Sagar Lonial, one of the authors of the report.
Time for a commerical break: incentive to invest
in new technologies
Emory has
established a new Investor Challenge Fund that will provide a match for
qualified investors who invest in promising technologies discovered by
Emory scientists. The eligible technologies, including drug candidates,
medical devices, and diagnostic tests, will have the potential for commercialization
through licensing to start-up companies.
Emory already provides proof-of-concept
funding, in-house services for licensing new technologies to companies,
assistance for new start-ups in the creation process, and some physical
space for new start-ups. The University also participates as a limited
partner in venture capital funds, such as the newly created $3.5 million
Georgia Venture Partners Fund, established by Emory, Georgia Tech, and
the University of Georgia.
“Supporting private investment in
our own research helps assure that the work of our scientists reaches
patients, where it can do good,” says medical school dean Thomas
Lawley.
The University has made big strides in moving
key discoveries from the laboratory to the marketplace over the past decade.
For example, Emory has launched 35 start-up companies and currently has
24 licensed therapeutic products in various stages of drug discovery,
clinical development, or regulatory approval.
Faculty
Leadership
Richard
Cummings, an internationally known expert in glycomics, is the new chair
of the Department of Biochemistry. He comes to Emory from the University
of Oklahoma, where he was chair of molecular biology.
Glycomics is the study of the carbohydrate
molecules produced by an organism, a major new research focus identified
by the NIH. Cummings has played a key role in the Consortium for Functional
Glycomics funded by the NIH. His research focuses on glycoconjugates,
the carbohydrate molecules and their associated proteins that permit cells
to communicate with and adhere to each other—transmitting and receiving
chemical, electrical, and mechanical messages that underlie all cellular
and bodily functions. His research focuses on the role of glycoconjugates
in cardiovascular biology, autoimmune diseases, and parasitology.
David Stephens, Schwartzmann Professor, director of infectious diseases,
and executive vice chair of medicine, has a new title and added responsibility
as executive associate dean for research. An expert on meningitis, Stephens
heads a lab that has led international efforts to define the molecular
basis for virulence of bacteria causing this disease. He helped found
what is now the Georgia Emerging Infections Program, a population-based
laboratory surveillance and clinical research program focused on bacterial
pathogens. He also led CDC’s clinical emergency response team in
defining clinical issues in prophylaxis, diagnosis, and treatment of anthrax.
He currently is principal investigator of the NIH-sponsored Southeastern
Regional Center of Excellence for Emerging Infections and Biodefense.
Stephen Warren, chair and William Patterson Timmie Professor of Human
Genetics at Emory, is the new president of the American Society of Human
Genetics. He is renowned for groundbreaking genetic discoveries, including
the identification of the cause of fragile X syndrome, the most frequently
inherited form of mental retardation.
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