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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