Scientific Report 2008
I am proud to
report on some of the many accomplishments at The Scripps Research Institute during
the past year. Our investigators on both coasts made extraordinary advances in their
fields, our education and community outreach programs continued to thrive, and Scripps
Research teams won major grants to fund innovative projects.
Despite the difficult funding environment
for science in general, scientists at Scripps Research won several large federal
grants in 2008, building on our cornerstone strengths of scientific excellence and
interdisciplinary collaboration. These grants are a validation of the quality of
the research on the California and Florida campuses.
The largest federal grant in 2008—and
in the history of the institute—was an $80 million award to expand efforts
to screen molecules for possible drug development at the Scripps Research Molecular
Screening Center. The 6-year grant from the National Institutes of Health (NIH)
provides funds to uncover "proof-of-concept molecules" that could bring
new treatments for many human diseases closer to reality. Led by Professor Hugh
Rosen, the recipients of the grant will use high-throughput robotics at the Florida
campus to test discoveries made in laboratories in California and Florida and in
other research institutions against various biological targets.
The NIH also awarded $20 million to the
Scripps Translational Science Institute, a collaborative program between Scripps
Research and Scripps Health and researchers at other institutions in San Diego.
The purpose of the grant, a Clinical and Translational Science Award, is to accelerate
the translation of scientific discoveries to improvements in medicine. In addition
to funding studies relevant to developing individualized treatment and prevention
strategies, the grant will support advanced research training. Led by Eric Topol,
the Scripps Translational Science Institute is 1 of only 4 California programs to
receive this type of funding and the first in Southern California.
The National Institute of Neurological
Disorders and Stroke awarded $7.6 million to investigators at the Florida campus
to develop the next generation of medications to treat Parkinson's disease.
Research funded by this 5-year grant will be led by Philip LoGrasso, associate professor
and senior director for drug discovery. He and his colleagues hope to advance the
potential treatment so that an application can be filed for an investigational new
drug, the first step in the lengthy clinical trials required by the Food and Drug
The National Institute on Drug Abuse
awarded $4 million to a group of investigators on the California campus for research
on the effects of chronic marijuana use, including influence on brain function and
the consequences of withdrawal. Scientists at the new Translational Center on the
Clinical Neurobiology of Cannabis Addiction, led by Barbara Mason, professor and
codirector of the Pearson Institute for Alcoholism and Addiction Research, will
help develop novel approaches for the prevention, diagnosis, and treatment of marijuana
Thanks to the generosity of individuals
and foundations, Scripps Research also received noteworthy support from the private
and nonprofit sectors in 2008, accelerating the progress of our research.
The International AIDS Vaccine Initiative,
a global nonprofit organization, awarded $30 million to Scripps Research to create
a new research center at the California campus that will be linked to a network
of research institutions in Africa, Asia, Europe, and the United States. The focus
of the center, led by Dennis Burton, a professor at Scripps Research and the scientific
director of the Neutralizing Antibody Consortium of the initiative, will be on expanding
efforts to find the crucial antibody-inducing components necessary to make an effective
vaccine against HIV and AIDS.
In another act of generosity and foresight,
San Diego philanthropist, businessman, and community leader John J. Moores contributed
the first donation, a gift of $2.1 million, to the Scripps Research $50 million
initiative to recruit new world-class researchers and to sustain and expand the
work of our current scientists. Moores, chairman and owner of the San Diego Padres
baseball team, has served as a member of the Scripps Research Board of Trustees
since 1997 and as chair of the board since 2006.
Miami physician, businessman, and philanthropist
Phillip Frost and his wife, Patricia Frost, an ardent supporter of education and
the arts, donated $1 million to the Florida campus. In recognition of their
donation, the foyer of the building that will house laboratories for a key component
of research in Florida, making strategic scientific discoveries and then expediting
their development into new drugs and treatments to improve human health, will be
named the Frost Lobby.
We are deeply grateful for all the support
we receive. We recognize that gifts and grants make possible our scientists'
extraordinary efforts to expand knowledge and improve human health.
Once again, scientists in our laboratories
have made extraordinary findings. Recent breakthroughs in 2008 are described in
the following list:
- Assistant Professor Erica Ollmann
Saphire and colleagues revealed the shape of the Ebola virus spike protein, which
is necessary for entry of the virus into human cells, bound to an antibody acting
to neutralize the virus. The structure provides a major step forward in understanding
how the virus works and may be useful in the development of Ebola virus vaccines
or treatments for patients infected with the virus.
- Huntington's disease has
no cure, or even treatments that can reverse or slow progression of the movement
deficits and cognitive dysfunction that occur with the condition. So, it was particularly
good news when Assistant Professor Elizabeth Thomas and colleagues showed that an
agent they developed has dramatic therapeutic efficacy and minimal toxicity in a
mouse model of Huntington's disease. The compound has been licensed for further
testing and development.
- Bruce Beutler, chairman of the
Department of Genetics; Ulrich Müller, a professor in the Department of Cell
Biology; and colleagues found that a mutation in a new gene, which they named COMT2,
causes a form of deafness that has nothing to do with structural proteins in the
inner ear, which are commonly altered in hereditary deafness. The finding that the
mutation affects an enzyme with a known catalytic function suggests how the deafness
caused by COMT2 might be preventable with novel drug therapy.
- Professor Wolfram Ruf and colleagues
uncovered a connection between blood coagulation and the immune system that may
have important implications for patients with sepsis, a severe and difficult-to-treat
disease that kills tens of thousands of in the United States each year. The scientists
identified a new cross talk involving the vascular coagulation system and certain
cells in the immune system. By disrupting this cross talk, they were able to rescue
mice from death due to sepsis.
- Professor Chi-Huey Wong and
colleagues developed a new 2-punch strategy against HIV infection and successfully
tested aspects of the strategy in the laboratory. The investigators created devices
they call glycodendrons that are designed to do 2 things at once: (1) inhibit the
transport of HIV from its traditional sites of entry into the body, preventing it
from moving deeper inside where it can infect immune cells, and (2) set up an immune
antibody response to a unique carbohydrate structure on the surface of the virus.
- Professor James Quigley his
group identified a potential new target for treating metastatic cancer in humans.
By blocking the action of the protein CD151, the team stopped cancer cells from
spreading from one site to establish new tumors elsewhere.
- Professor Claes Wahlestedt and
colleagues discovered a new gene involved in fragile X syndrome, a condition with
many signs and symptoms similar to those of autism. The discovery of the new gene,
FMR4, may lead to new tests or treatments for several neurologic disorders.
- Assistant Professor Timothy
Tellinghuisen and his colleagues discovered a method to disrupt the production of
infectious virus particles that cause hepatitis C, a blood-borne liver disease.
This discovery might be a first step in developing new and more effective therapies
against hepatitis C virus. Current antiviral agents are ineffective for many patients
infected with the hepatitis C viral strains most prevalent in the United States.
- Professor Raymond Stevens and
his group determined the structure of the human A2A adenosine receptor, sometimes
referred to as the "caffeine receptor," which is a member of the large,
medically important family of G protein—coupled receptors. The findings could
lead to the development of a new class of therapeutics for treating numerous neurologic
disorders, including Parkinson's and Huntington diseases.
- Professor Phil Baran and investigators in his laboratory developed an inexpensive new method for economically producing a promising pharmaceutical steroid. The molecule, cortistatin A, which was isolated in 2006 from a marine sponge,
has great promise for treating conditions ranging from macular degeneration to cancer.
- Associate Professor Mark Mayford
and colleagues showed that in a situation that required learning, neurons in the
brain's memory hub, the hippocampus, had an increased ability to retain newly
synthesized proteins called AMPA receptors.
- Using samples from survivors
of the 2005—2006 "bird flu" outbreak in Turkey, an international
team, including researchers at Sea Lane Biotechnologies and me, created the first
comprehensive monoclonal antibody libraries against avian influenza virus (type
H5N1) These antibody libraries may be useful in developing a therapy that could
stop an influenza pandemic and provide treatment to those infected and in pointing
the way to the development of a universal flu vaccine.
- Kim Janda, Scripps Research
professor and member of the Skaggs Institute for Chemical Biology; Eric Zorrilla,
Scripps Research associate professor; and colleagues discovered a catalytic antibody
that degrades a known appetite stimulant. The antibody works against the gastric
hormone ghrelin, which has been linked to weight gain and fat storage. These findings
may lead to a novel treatment for obesity.
Commitment To Education
In addition to our dedication to research,
we are committed to educating the next generation of scientists. At our commencement
ceremony in May, 28 doctoral candidates graduated from the Kellogg School of Science
and Technology, and Scripps Research trustee Claudia S. Luttrell was awarded an
honorary degree. The school can now boast of more than 300 accomplished alumni.
Among these, 3 alumni—2 from this year's graduating class—conducted
their studies on the Florida campus.
The fall brought a record number of entering
graduate students to both the Florida and the California campuses. In Florida, an
unprecedented 75% of offers extended to students were accepted: 9 of 12 offers made.
Of these 9 students, 4 are from Florida universities.
In addition, we continue to build programs
to support our valued postdoctoral fellows, and to make strides in reaching out
to high school students and teachers to share our excitement about the scientific
The year brought a variety of transitions
for people at Scripps Research. We welcomed international business leader and entrepreneur
Amin J. Khoury to the board of trustees. Khoury, who is chair of the board and chief
executive officer of B/E Aerospace, Inc., of Wellington, Florida, brings his talents
as a business executive and his experience as a founder of companies in aerospace,
scientific instruments, medical services, and medical devices.
Roy Smith from Baylor College of Medicine
joined Scripps Research at the Florida campus to head our new Department of Metabolism
and Aging. I look forward to his contributions to this exciting field, which is
advancing our knowledge of aging and age-related diseases.
Hollis Cline joined the California campus
as part of the Departments of Cell Biology and Chemical Physiology. Dr. Cline's
expertise in the neuroscience of vision will be a significant contribution to our
world-class neuroscience research.
Professor Jeanne F. Loring, renowned
in the field of stem cell research, joined the faculty at the California campus.
Dr. Loring will apply her extensive knowledge and experience to lead a team to new
discoveries that will benefit human health.
Richard Ulevitch, an internationally
renowned researcher in the field of innate immunity, stepped down as chair of the
Department of Immunology this year. He is continuing to maintain a laboratory at
Scripps Research as professor and chair emeritus while joining 5AM Ventures of Menlo
Park, California. Professor Argyrios Theofilopoulos is acting chair as we conduct
an international search to fill this position.
Ernest Beutler, chair of the Department
of Molecular and Experimental Medicine since 1978, stepped down from this role in
2008. Filling the position is Jeffery Kelly, Lita Annenberg Hazen Professor of Chemistry
and a member of the Skaggs Institute for Chemical Biology, who also recently became
chair of the board of trustees of the Skaggs Institute for Research (one of the
Skaggs family's major mechanisms for its philanthropy). It is with great sadness
I report that Ernie Beutler, who was planning to continue to run his research program,
passed away in October. His passing is a great loss to science, to Scripps Research,
and to all who knew and worked with him during his long, brilliant career.
Assuming the deanship of the Kellogg
School from Jeff Kelly is Professor Jamie Williamson, also a member of the Skaggs
Institute, who will build on his 7 years as associate dean and 10 years as a Scripps
Research faculty member to lead this top-ranked graduate
program into the future.
In 2008, our esteemed faculty again received
many honors and awards.
- Three of our faculty members,
Bruce Beutler, Mike Oldstone, and Peter Wright, were acknowledged for their outstanding
research achievements by election to the National Academy of Sciences. Their election
brings to 19 the number of National Academy members among our faculty. To have had
3 such deserving researchers elected in a single year is truly remarkable for an
organization of our size.
- Professor Albert Eschenmoser
won the Benjamin Franklin Medal in Chemistry. Franklin Institute Awards are given
for outstanding achievements that have enhanced the quality of human life and deepened
our understanding of the universe; Dr. Eschenmoser was recognized for his research
on nucleic acid structure, leading to the understanding of why RNA and DNA have
the structures they do.
- Professor Ian Wilson was showered
with honors, including an honorary degree from the University of St. Andrews in
recognition of achievements "at the forefront of research to understand the
immune system and influenza"; election as a corresponding fellow of the Royal
Society of Edinburgh, Scotland's National Academy of Science and Letters; and
election to the board of directors of the Keystone Symposia.
- Professor Carlos Barbas received
the 2009 Tetrahedron Young Investigator Award, Bioorganic and Medicinal Chemistry,
an award for individuals less than 45 years old who have exhibited "exceptional
creativity and dedication" in their fields. In addition, Dr. Barbas was chosen
for the American Chemical Society Arthur C. Cope Scholar Award, which recognizes
excellence in organic chemistry.
- Jeffery Kelly received the American
Peptide Society Vincent du Vigneaud Award, sponsored by Bachem, Inc., for "fundamental,
visionary research on folding and aggregation processes in peptides and proteins,
and for courageous, insightful exploration of the biological and medical implications
of his discoveries."
- Sandra Schmid, chair of the
Department of Cell Biology, was chosen by the American Society for Biochemistry
and Molecular Biology to receive the William C. Rose Award, which recognizes outstanding
contributions to biochemical and molecular biological research and a demonstrated
commitment to the training of younger scientists.
- Associate Professor Gaudenz
Danuser won the Michael and Kate Bárány Award for Young Investigators
from the Biophysical Society for his "outstanding seminal contributions in
diverse areas of cell biology, particularly . . . our understanding of cell cytoskeleton
dynamics and function using speckle microscopy."
- Assistant Professor Ian MacRae
was selected as a 2008 Pew Scholar in the Biomedical Sciences by the Pew Charitable
Trusts and the University of California at San Francisco. Dr. MacRae will receive
4 years of support for his research, which combines structural biology, biochemistry,
and cell biology to understand mechanisms of gene regulation by RNA interference.
As we look forward to celebrating the
opening of the permanent Florida campus in February 2009, I am delighted to take
this moment to appreciate the many, significant accomplishments that have brought
us this far. Thank you to trustees, donors, friends, faculty, staff, postdoctoral
fellows, and students of Scripps Research for your dedication, hard work, and vision.