Download The Institute for Cancer Biology at Yale`s West

The Institute for Cancer Biology at Yale’s West Campus
The Science Institutes at Yale’s West Campus
Cancer Biology Microbial Diversity Nanobiology Systems Biology Chemical Biology Energy Sciences
T
he right medicine for the right person at the right time—
personalized medicine holds extraordinary promise for the
treatment of cancer. Today’s science revolution is providing
the tools researchers need to isolate the genes implicated in
cancer as well as ways to turn those genes on and o≠. In the clinic, doctors
will soon evaluate, as a matter of routine, why an individual’s tumor is
malignant and then select a cancer therapy that is tailored to the genetics
and history of the patient. In many cases, scientists hope to fight even
metastatic cancers with this approach.
Under the leadership of founding director Joseph Schlessinger, the William
H. Pruso≠ Professor and chair of Pharmacology, the Institute for Cancer
Biology at Yale University is dedicated to finding the
causes and potential treatments for cancer. Assembling
After seventy years
of chemotherapy and a team of the field’s foremost scientists on Yale’s West
Campus, the Institute will apply the tools of molecular
billions of dollars
biology, genetics, and cell biology to understand cellular
invested in research
function at the genetic level—asking how cells function,
and discovery, a new what happens when things go wrong, and which
paradigm—personavenues might o≠er new treatments for disease. The
alized medicine—at
Institute is interdisciplinary in its make-up, drawing
last raises the hope
on the best people across Yale’s programs of science
and medicine, and it acts as a new research arm of the
that cancer may be
Yale Cancer Center.
cured within our
lifetime.
The addition of this Institute to Yale’s larger biomedical
research enterprise brings extraordinary capacities to
make personalized medicine a reality, especially in the emerging areas of
cancer genomics and proteomics, signal transduction, and tumor immunotherapy. Moving forward, the Institute will be one of a handful of U.S.
programs at the forefront of cancer research, and it will play a key role in
defining Yale as one of the nation’s top five hospital-based cancer programs.
Most important, it will bring us another step closer to our chief goal—the
hope that cancer may be cured within our lifetime.
Putting the
Brightest Minds
to Work on a
Single Problem
Yale University stands among the world’s leading global research institutions, able to
mount top-ranking programs of teaching and research in the physical, biological, engineering, and medical disciplines. The Yale Cancer Center, which unites the e≠orts of the
School of Medicine and the Smilow Cancer Hospital at Yale-New Haven, is one of a
select group of comprehensive cancer-care centers designated by the National Cancer
Institute, a distinction maintained for over 30 years.
In this setting, the Yale Institute for Cancer Biology o≠ers a special, powerful model for
solving an urgent problem: it places specialized tools and vast resources in the hands of
a scientific team focused on a single, common goal. The Institute, bringing together
up to twelve principal investigators and a supporting team of 120 post-doctoral fellows,
graduate students, and sta≠, will focus on the fundamentals of personalized medicine
for cancer. For example, scientists in genomics will work to understand the unique profile
of every tumor, and they will share space with teams in cell biology, which will focus on
the pathways that lead to tumor formation, and with teams in chemical biology, which
will work on synthesizing new molecular entities that can interrupt these cancer forming
pathways. This approach will connect specialists in virology, genetics, immunology, and
cell signaling with each other and with clinicians who can help translate findings into
improved programs of clinical testing and patient care.
Researchers believe that this coordinated focus on the basics of cancer development
will accelerate the pace of discovery, rapidly identifying and developing new avenues
for cancer treatment. Equally important, this work will lead to the routine use of
personalized medicine in clinical settings, creating a model within the Smilow Cancer
Hospital that can be replicated across the country.
Chemical
Biology
Microbial
Diversity
Cancer
Biology
SMD
GA
Systems
Biology
HTCB
Nanobiology
Energy
Sciences
Linking to a
Larger Research
and Clinical
Enterprise
The Institute for Cancer Biology is one component of an integrated vision for cancer
care and research at Yale. Within the umbrella of the Yale Cancer Center, the Institute
has strong programmatic links to both the Faculty of Arts and Sciences and the School
of Engineering & Applied Science. These links encourage scientific initiatives across the
University, allowing basic scientists, for example, to build on information obtained in
the clinic, and vice versa. This approach will bring the full power Yale’s research enterprise
to bear on significant questions in the lab and at the same time speed the development
of potential cancer therapies through clinical evaluation.
Yale’s West Campus is an ideal setting to connect the genomic screening of clinical samples
with basic research on cellular function. This 136-acre site features 454,000 square feet of
laboratory space configured for research in biomedical science. In addition to the Institute
for Cancer Biology, the University is establishing a number of new centers and programs
that complement cancer research:
•High-throughput screening centers for small molecules and siRNAs, where researchers
can quickly evaluate chemical compounds and cellular pathways for their role in halting
tumor formation and progression
•A next-generation DNA sequencing center, equipped with thirteen gene sequencers for
basic and applied research into the genetics of cancer as well as a host of human diseases
•An integrated cluster of institutes in microbial diversity, chemical biology, systems
biology, energy sciences, and nanobiology
Together, these interrelated centers and programs will sustain the kind of multidisciplinary
approach needed to successfully combat cancer. Over time, Yale hopes to augment West
Campus with clinical programs of outpatient oncology care and a translational cancer
research unit.
Yale has an extraordinary history and strength in the areas
of basic science and cancer research. Its School of Medicine
was home to the country’s first university-based medical
oncology section, and its faculty has pioneered breakthrough cancer treatments that include the first successful
use of chemotherapy in 1942. Work now under way at Yale
illustrates the promise of current science in the understanding, diagnosis, and treatment of cancer.
Do cancer cells have vulnerabilities not seen in
healthy cells?
For decades, scientists have grappled with the toxicity of
cancer treatments; too often, drugs used to shrink tumors
have been harmful to healthy tissues
as well. To sidestep this problem,
geneticist Peter Glazer is studying
ways that cancer cells di≠er from
healthy cells.
“In contrast to healthy cells, ” explains
Glazer, “growing tumors often lack an
adequate supply of oxygen. We hope
to develop cancer-killing compounds
that work only in low-oxygen conditions, leaving healthy
cells untouched.”
Glazer’s work with low oxygen, or hypoxia, dovetails with
another of his research areas. In many cancers, genes needed for DNA repair are silenced, and if an individual inherits
a bad gene for DNA repair, he or she is even more vulnerable
to malignancies. “It turns out that hypoxia down-regulates,
or silences, DNA repair mechanisms,” says Glazer. “So we’re
using the West Campus chemical screening facility to find
compounds that are lethal to DNA repair-deficient tumors,
whether they’re hypoxia-induced or the result of a genetic
deficiency.” Already, his team has scored “hits” with several
chemicals, including existing drugs that reveal an unexpected potential to treat breast cancer. And Glazer was
surprised to find that some Chinese herbal remedies are
e≠ective against DNA repair-deficient cells. “The coordination of West Campus core facilities is making it easier
for us to study these compounds,” he says.
Can viruses help us shut down the pathways implicated
in tumor development?
Viruses cause fifteen percent of all human cancers. For
molecular virologist Daniel DiMaio, this suggests an
opportunity to develop novel cancer treatments. A vaccine
for human papillomavirus, or HPV, is
now used to prevent many cases of
cervical cancer. But HPV is implicated
in many head and neck cancers as
well, and DiMaio predicts that in the
not-too-distant future, vaccines will
not just prevent, but also treat a range
of these diseases as well as other
cancers with viral causes.
DiMaio is also deeply interested in the ability of viruses to
exploit cells for their own propagation. “By studying how
viruses interact with cells, we can learn about basic cell
function and cell growth,” he says. This work in turn opens
new ways for scientists to control cellular activity. “Viruses
are teaching us how to turn specific pathways on and o≠,”
says DiMaio. “We are working to reprogram viral proteins,
for example, to turn o≠ HPV oncogenes in cancer cells or
to attack receptors for HIV, which can predispose infected
people to cancer. These techniques hold promise for preventing or treating cancer.” DiMaio is optimistic that a
cadre of cancer investigators working side-by-side at West
Campus will speed the development of new breakthroughs
in cancer prevention, diagnosis, and treatment.
Cottontail rabbit papillomavirus
Can we use the cell’s internal signaling system to halt
tumor growth?
At MIT in the 1980s, David Stern was part of a team that
controlled rat tumors using an anti-Neu antibody. This
work was foundational for the development of Herceptin, a
breakthrough drug that attacks breast
cancers caused by the human version
of the Neu gene. But Stern is quick to
lament the rate of progress since then.
“While we’ve had this viable model
for developing cancer treatments, the
problem has been more complex than
investigators initially hoped,” he says.
How do genes define the timing of cell growth in a
developing organism?
Developmental biologist Frank Slack devotes his time to
the fundamental question of how a ball of cells can grow
into a healthy organism. In 1997, this curiosity led him to
microRNAs, tiny RNA
molecules that control
gene expression in the
worm C. elegans—and,
as it turns out, human
beings. When Slack knocked
out one of the worm’s 120
microRNA genes, another
gene, ras, was overexpressed, leading to out-of-control growth of the animal’s
skin cells. Scientists soon discovered a similar mechanism
in mice, and in 2000, Slack was part of the group that found
the first human microRNAs. Today it is clear that RAS is
essential to controlling cell division in humans, and the
gene is strongly implicated in lung cancer. Slack’s discovery
may lead to therapeutics that regulate RAS expression in
human cancers.
In his most recent work, Slack has been experimenting with
microRNAs to regulate oncogenes in mice. His team has
been able to shrink existing tumors in mice with full-blown
cancer, a feat he hopes will one day be replicated in humans.
“We know exactly how a mouse gets cancer,” says Slack,
“but the causes in humans are much more complicated. We
need to better understand the role of microRNAs and solve
issues of drug delivery and toxicity, but human trials of this
therapy are certainly in our future.”
Each cancer develops uniquely within each patient, and
there are often multiple changes in hormone receptors or
the signaling pathways they regulate. “You need the ability
to comprehensively assess each tumor to understand which
genes and pathways are affected and present good targets
for therapy,” Stern says.
At last, Stern hopes, science has the tools to manage this
complexity: “We’re now able to evaluate all the major
features that contribute to oncogenesis, not just individual
elements. Cancer genotyping and functional testing can
be used to broadly assess changes in individual tumors in a
way that can lead to better treatments.”
Today, Stern continues to work on breast cancer, and he
is also associated with the Yale SPORE in Skin Cancer, a
consortium of biologists, surgeons, oncologists, and pathologists who apply this “big picture” approach to the study of
melanomas. Together, Stern and his colleagues are working
to document which receptors and signaling pathways are
activated in these two important diseases. Already the
researchers have turned up new pathways as well as known
pathways acting in combination. “It won’t be long before we
understand the major changes driving common cancers,”
he says. “And it is very likely that we can target some of
these mechanisms using drugs already in clinical trials or
clinical use.”
Supporting the
Institute for
Cancer Biology
While chemotherapy has been in use for almost 70 years, and billions of dollars have
been invested in research and discovery, a cure for cancer has been elusive. Researchers
in the Institute for Cancer Biology seek to leverage Yale’s historic commitment and
achievements in basic and translational research to advance our understanding of cancer,
so that the disease can be ameliorated within our lifetime. Donors are key to this mission.
As the work of the Institute unfolds, Yale seeks new endowment to attract the world’s
top cancer scientists and to support their research at the highest level, with equipment,
specialized sta∞ng, and program funds. Gifts will speed the start-up of the Institute
and ensure continuing resources for its work in the years to come. Please join in this
vital undertaking.
Institute for Cancer Biology
$50,000,000 1 opportunity
A transformative gift of $50,000,000 to name the Institute for Cancer Biology will allow
the Institute director to recruit leading scientists, invest in cutting-edge technologies, and
initiate creative research programs that will lead the scientific community in research
and discovery.
Professorship
$3,000,000 3 opportunities
To drive path-breaking research at the West Campus, Yale aims to recruit outstanding
scholars who will advance basic research, scientists who will find new ways to identify
and treat disease, and academic leaders who will foster the development of these new
ideas and techniques. Endowed professorships exist in perpetuity and provide lasting
recognition of whomever the donor chooses to honor.
Yale Scholar
$2,500,000 9 opportunities
The University and the School of Medicine have joined forces to establish a new initiative
known as the Yale Scholars Program. Designed to attract the finest and most promising
young scientists to Yale’s faculty, the program will provide institutional support of
$250,000 per year to cover the start-up costs of a new faculty member’s research. In their
fifth year, these scientists are expected to be su∞ciently established to generate funding
from federal or private sources, and the Yale Scholar position will be o≠ered to a new
scientist entering the field, repeating the cycle and further enlarging our pool of top-rate
faculty. A named Yale Scholar position can be established with a gift of $2,500,000, to
be matched 1:1 by the University. The donor will receive reunion credit for the full
$5,000,000 endowment.
Director’s Fund
$ 100,000–$3,000,000
Multiple opportunities
To learn more
There are many ways of giving to the Institute for Cancer Biology.
For more information, please visit www.giftguide.yale.edu
or contact:
Joan E. O’Neill
Vice President for Development
[email protected] or 203.432.5515
Patricia Pedersen, ph.d.
Associate Vice President and Director, Corporate and Foundation Relations
[email protected] or 203.436.8518
08/12