Discovering and developing new treatments for disease is a challenging, time-consuming, and expensive endeavor. For every drug that eventually makes it to the pharmacy, hundreds of compounds fail to deliver results and millions of dollars are spent without a direct return on investment. However, in these economically challenging times, existing drugs and compounds—whether in development, already on the market, or even ones that have failed clinical trials due to lack of efficacy—are being re-examined by pharmaceutical companies and research institutions. The goal of this approach—called drug repurposing— is to find potential new uses for these drugs.
High-throughput drug screening platforms in Sanford-Burnham's Conrad Prebys Center for Chemical Genomics will be used to screen existing drugs for new applications.
Glioblastoma multiforme (bright ring at right), as seen by magnetic resonance imaging (MRI)
We are pleased to announce our role in a new multidisciplinary study aimed at finding novel brain cancer therapies. The team, led by the Translational Genomics Research Institute (TGen), includes Sanford-Burnham Medical Research Institute, the Van Andel Research Institute (VARI), and the Intellectual Property & Science division of Thomson Reuters.
A $4.5 million grant from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), will fund the five-year search to find new ways of treating glioblastoma multiforme, the most common and lethal form of brain cancer. Primary brain tumors are among the top 10 causes of cancer death in the U.S., and more than 80,000 Americans have primary malignant brain tumors.
TRI grand opening speakers (from left to right): John Reed, Terry Owen, Dan Kelly, Steve Smith, Lars Houmann, Des Cummings, Don Jernigan
“My goal is to cure diabetes,” Steven Smith, M.D., scientific director of the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes (TRI), said boldly at the opening ceremony of the TRI’s new state-of-the-art facility in downtown Orlando on March 27. “We believe that personalized medicine is our best shot at discovering cures for our most serious health problems like diabetes.”
The ceremony’s highlight was the unveiling of a spectacular nine-foot double-helix DNA structure that will be placed at the main entrance of the building, symbolizing the fundamental research being conducted at the TRI, as well as the synergies and collaborations the TRI represents. Selected board members and presenters each added one illuminated “bar,” representing a nucleotide, to the double helix.
“This is one of those rare times when the reality far exceeds the dream,” said John Reed, M.D., Ph.D., CEO of Sanford-Burnham. “The TRI is a wonderful opportunity for our organization, which will bring more and more to life our slogan From Research, the Power to Cure. We’re very excited about this opportunity to take our relationship with Florida Hospital to the next level.”
New TRI Facility in Downtown Orlando
Florida Hospital and Sanford-Burnham today celebrate the opening of the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes’ (TRI) new state-of-the-art facility in downtown Orlando, Fla., dedicated to the advancement of a new paradigm of personalized approaches to researching and treating diabetes and obesity.
“We are witnessing the rise of personalized medicine, most notably in cancer. Our goal at the TRI is to accelerate the advancement of personalized medicine in diabetes and obesity,” said Steven Smith, M.D., Sanford-Burnham professor and scientific director of the TRI. “We are working to rapidly expand knowledge of complex genetic and molecular causes of diabetes and obesity so that we can better define disease subpopulations. By working independently and in partnership with industry, we hope to develop therapies and treatment approaches tailored to those subpopulations. Our ultimate goal is that our discoveries will someday lead to cures for certain patients.”
Ranjan Perera, Ph.D.
Melanoma is a type of skin cancer in which melanocytes, the pigment-producing cells in the skin, keep growing even when they shouldn’t. More than 100,000 new cases of melanoma are diagnosed each year in the U.S. and almost 80 percent of melanoma patients die from their disease, making melanoma the most deadly type of cancer. Because melanoma can spread very quickly, early detection and treatment give patients the best chance for survival.
The development of melanoma involves a complex interplay between environmental factors and alterations in gene expression (the way genes are turned on or off). While exposure to UV radiation is a key risk factor for melanoma development, it’s unclear how UV radiation influences which genes are turned on or off in skin cells—a process known as gene expression. This is exactly the question that interests Ranjan J. Perera, Ph.D., scientific director of Analytical Genomics and Bioinformatics and associate professor in the Diabetes and Obesity Research Center at Sanford-Burnham in Lake Nona, Orlando.
Orexin targets brown fat cells
Discoveries made in the laboratories of Sanford-Burnham will, for the first time, advance to the clinical research stage involving human studies at the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes (TRI). The research will focus on orexin, an appetite-inducing hormone produced in the brain, which appears to resolve obesity without requiring a reduction in food consumption or elevation in physical activity. This research exemplifies the translational research focus at Sanford-Burnham and the TRI – advancing science from laboratory bench to patient bedside. The studies will provide insight into individual responses and contribute to the development of personalized therapies for treating metabolic diseases – a focus area for both the TRI and Sanford-Burnham.
Appetite-suppressing drugs have traditionally been the basis of weight-loss treatments since obesity is thought to be caused by excessive energy intake and low physical activity. However, appetite suppressants can produce unacceptable side effects and, after the treatment ends, patients usually the weight they lost. Recent data indicate that orexin leads to weight loss by releasing excess energy as heat instead of storing it.
Eric Green, M.D., Ph.D., director of the National Human Genome Research Institute at the NIH
At Sanford-Burnham’s 3rd annual Rare Disease Day Symposium, held today in La Jolla, Calif., keynote speaker Eric Green, M.D., Ph.D., director of the National Human Genome Research Institute at the NIH, spoke about genomic medicine. Sometimes called “personalized medicine,” or even “precision medicine,” Dr. Green defined this revolutionary field as the idea that health care can be tailored to the individual based on his or her own genomic information.
Dr. Green was there when the human genome was first sequenced in 2001 and he’s now leading the next step—figuring out how to use that information. In his talk, Dr. Green outlined five active research areas that are taking us from what he called “helix to health:”
Sanford-Burnham CEO John Reed (right) interviewing NIH Director Francis Collins for Medscape
In an exclusive Medscape interview, Francis Collins, M.D., Ph.D., director of the National Institutes of Health, speaks to John Reed, M.D., Ph.D., Sanford-Burnham’s CEO, about the value of science in medicine and the most exciting developments on the horizon.
Cerebellar stem cells engineered to express Myc and mutant p53 (shown here) give rise to aggressive tumors that resemble a particularly malignant form of human medulloblastoma, providing a new model that will help scientists develop more effective therapies for this disease.
Children with a devastating brain cancer called medulloblastoma develop tumors in a region of the brain called the cerebellum, which plays an important role in motor control. Seventy-five percent of children with the disease survive after aggressive surgery, radiation, and chemotherapy—but side effects can be severe, leading to cognitive deficits, endocrine disorders, and the development of other cancers later in life.
Sanford-Burnham scientists have now developed a new mouse model for studying medulloblastoma. The animal model mimics the deadliest of four subtypes of the human disease, a tumor that is triggered by elevated levels of a gene known as Myc. The study, published February 13 in the journal Cancer Cell, also suggests a potential strategy for inhibiting the growth of this tumor type. This achievement marks an important milestone toward personalized therapies tailored to a specific type of medulloblastoma.
“Being able to use an animal model as a tool to test treatments has been very valuable in medulloblastoma, as in other types of tumors. But for Myc-associated tumors, that hasn’t been an option because there hasn’t been a model of the disease. This is the first step to developing therapies for this type of tumor,” said Robert Wechsler-Reya, Ph.D., director of the Tumor Development Program in Sanford-Burnham’s National Cancer Institute-designated Cancer Center, member of the Sanford Consortium for Regenerative Medicine, and senior author of the study.
Sanford-Burnham, Moffitt and Florida Hospital form Personalized Medicine Partnership of Florida
Sanford-Burnham, Moffitt Cancer Center, and Florida Hospital announced today that they will collaborate to create a Personalized Medicine Partnership of Florida (PMP Florida). The partnership will conduct research to speed up discovery and develop new treatments in the areas of cancer and metabolic diseases, including obesity, diabetes, and cardiovascular disease.
The organizations will utilize new molecular and genomic technologies to discover, translate, and personalize interventions for preventing and treating diseases more efficiently to improve outcomes, while reducing costs. The partnership will speed up the discovery and development of new treatments by bringing together the complementary strengths of Florida Hospital’s large patient population and clinical research expertise; Sanford-Burnham’s fundamental research expertise and technology platforms; and Moffitt’s biospecimen bank (samples of tissue, cells, blood, etc.), data warehouse, and personalized medicine capabilities.
Kristiina Vuori, M.D., Ph.D., Sanford-Burnham’s president and director of the Institute’s NCI-designated Cancer Center (Photo by Nadia Borowski Scott)
Sanford-Burnham’s president, Kristiina Vuori, M.D., Ph.D., was named today as part of a new “Dream Team” to find innovative new ways to fight melanoma using a personalized medicine approach.
The Dream Team researchers will receive three years of funding from Stand Up To Cancer and the Melanoma Research Alliance. The newly funded project, which will receive a grant of $6 million, will not only explore a personalized medicine approach to treating metastatic melanoma, but may also lay the groundwork for fighting many other tumor and disease types. Stand Up To Cancer is a program of the Entertainment Industry Foundation, a charitable organization that has raised more than $100 million for cancer research in the past two years, much of it in connection with nationally televised fundraising specials.
“This is a test case to determine whether personalized medicine can become a reality. It’s our hope to be able to treat a patient with melanoma based on that person’s own molecular profile—an approach that’s likely to be more effective and have fewer side effects than current treatments,” said Vuori, who also directs Sanford-Burnham’s National Cancer Institute-designated Cancer Center. “Most importantly, our approach may represent improved survival for this patient group that currently has limited treatment options.”
CEO Dr. John Reed (left) and Congressman Duncan D. Hunter
Sanford-Burnham often welcomes public figures or community leaders onto its campuses to share the work taking place at the Institute. Congressman Duncan D. Hunter, U.S. Representative for California’s 52nd congressional district, expressed his gratitude at having drug discovery illuminated for him during a recent visit to the Institute’s La Jolla campus.
During his tour, Congressman Hunter met with Brandon Nelson, manager of the Stem Cell Core, one of Sanford-Burnham’s valuable Shared Resources. Nelson presented some recent advances in stem cell biology, including how researchers are using induced pluripotent stem (iPS) cells to generate heart and nerve cells. With this tool, scientists are able to model diseases in a dish and test potential new medicines. Congressman Hunter even took a look at beating cardiomyocytes (heart cells) under a microscope.
Neurons (Image courtesy of the Lipton lab)
Imagine the ability to take skin cells from a patient with Alzheimer’s disease, convert them directly into brain cells, and then study how the disease progresses in those cells—which still contain the patient’s DNA—all in the lab, with minimal invasiveness on the part of the patient. Then imagine taking those same brain cells and testing novel but risky drugs that could cure the devastating disease—again, in the safety of a dish in the lab.
Researchers are on their way to achieving this remarkable milestone. Dr. Stuart Lipton at Sanford-Burnham, Dr. Sheng Ding at the Gladstone Institutes, and their collaborators recently figured out how to reprogram skin cells directly into functioning neurons. The study was published online July 28 in the journal Cell Stem Cell.
“This technology should allow us to very rapidly model neurodegenerative diseases in a dish by making nerve cells from individual patients in just a matter of days, rather than the months required previously,” Dr. Lipton says in a statement released by the Gladstone Institutes.
The paper is one of several recent studies that are all zeroing in on a long-sought-after advance in stem cell science: the potential to obtain unlimited numbers of brain cells from an easily accessible tissue such as the skin.
NeuroMap was founded by (left to right): Daniel Norton, Dr. Alexey Terskikh, Dr. Dmitry Sivtsov and Dr. Andrew Rabinovich. (Photo by Sean M. Haffey, courtesy of San Diego Union-Tribune)
By Peijean Tsai
When a person is diagnosed with depression, pinpointing the right treatment is typically a trial-and-error process that frustrates both doctors and patients. Chronic symptoms interrupt everyday life while the patient seeks an effective remedy.
To address this challenge, NeuroMap, an early-stage company, is developing assays using induced pluripotent stem cells (iPSCs) to accurately predict how individuals with major depressive disorder (MDD) will respond on a personal level to medications, such as selective serotonin re-uptake inhibitors (SSRIs), the most commonly prescribed antidepressants.
“Some will have to go for months or years to find the right drug, and that’s what we’re trying to eliminate,” says Sanford-Burnham’s Dr. Alexey Terskikh, who founded NeuroMap with Dr. Dmitriy Sivtsov, a psychiatrist at the University of California, San Diego (UCSD) School of Medicine, computer scientist Dr. Andrew Rabinovich and Daniel Norton of UCSD’s Rady School of Management.
This novel concept – personalized depression therapeutics based on Sanford-Burnham technology – is what catapulted NeuroMap to win first prize earlier this month at the 5th Annual UCSD Entrepreneur Challenge’s Business Plan Competition, one of three contests the organization holds each year. The competition was judged by professionals from San Diego’s technology and entrepreneurial communities and presented before a public audience. The honor also awarded the startup company $57,000 in cash and entrepreneurial services, which Dr. Terskikh says will help move the company forward with its efforts to secure funding from government and private sources.
Dr. Steven Smith, Scientific Director for the Florida Hospital Sanford-Burnham Translational Research Institute, cares for a patient.
In 2003, the completion of the human genome project gave us an unprecedented amount of genetic information. From this, a new clinical concept is emerging: personalized medicine.Conventional medical care generalizes treatment to all patients with a particular disease. But since a disease is as individual as the person who has it, casting a wide therapeutic net has its limitations. For one, patients with a certain genetic makeup might not respond to a particular drug as well as patients with different genetics, or they might experience different side effects. As personalized medicine becomes a reality, it could rectify these less-than-ideal situations.
From the diagnostic point-of-view, personalized medicine is a shift from reactive to proactive. Based on a person’s health, genetic, and environmental profiles, doctors practicing personalized medicine could assess a patient’s risk for acquiring a genetic disease before any symptoms develop. This might allow them to target the specific genes that account for illness (the BRCA1/BRCA2 genes that predispose a woman to breast cancer, for example), incorporate a prevention strategy, and monitor those genes over time. When it comes to treatment, personalized drugs could be prescribed based on an individual’s molecular “build” and targeting treatment where it will do the most good and the least harm.