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.
Sanford-Burnham CEO John Reed (right) interviewing NIH Director Francis Collins for Medscape
Jennifer Yashari, M.D., both a doctor and a patient, will represent the Neuromuscular Disease Foundation at Sanford-Burnham's annual Rare Disease Day Symposium on February 24.
On February 24, we are holding our 3rd Annual Rare Disease Day Symposium in La Jolla, Calif. One of the speakers will be Jennifer Yashari, M.D., representing the Neuromuscular Disease Foundation. Jennifer is not only a doctor, she’s also a patient. Read excerpts from her story below and join us for the main event next week. If you can’t make it, check back here the following week for video of each talk and more stories.
I grew up being told one thing over and over again by my parents, “All that matters is that you’re healthy. Nothing is as important as your health.” I never fully understood or appreciated the extent to which that was true until six years ago, when I became someone with a disease…
Kristiina Vuori, M.D., Ph.D., Institute president and director of Sanford-Burnham's NCI-designated Cancer Center (center), with NCI-CBC leadership and participants
Where do new medicines come from? The first step in the drug discovery process often involves screening small molecules (chemicals) to determine their potential to produce innovative biological research tools. Sanford-Burnham’s Conrad Prebys Center for Chemical Genomics uses robotic technology to sift through chemical compounds by the millions to find the few that could potentially be developed into new medicines
Structure of bacterial flagellin bound to TLR5
To invade organisms such as humans, bacteria make use of a protein called flagellin, part of a tail-like appendage that helps the bacteria move about. Now, for the first time, a team led by scientists at The Scripps Research Institute and Sanford-Burnham Medical Research Institute has determined the 3D structure of the interaction between this critical bacterial protein and an immune molecule called TLR5, shedding light on how the body protects itself from such foreign invaders.
The study, published February 17 in Science, not only helps decipher the molecular mechanism underlying TLR5 recognition and function, but it also advances knowledge that’s key to the design of new therapeutics.
Taste receptors (green) in pancreatic insulin-producing beta cells (red). Nuclei are shown in blue.
Taste receptors on the tongue help us distinguish between safe food and food that’s spoiled or toxic. But taste receptors are now being found in other organs, too. In a study published online February 6 by the Proceedings of the National Academy of Sciences, Sanford-Burnham researchers discovered that beta cells in the pancreas use taste receptors to sense fructose, a type of sugar. According to the study, the beta cells respond to fructose by secreting insulin, a hormone that regulates the body’s response to dietary sugar.
“Before this study, fructose’s effect on insulin release was not appreciated. Fructose, and especially high-fructose corn syrup, is found in everything from sodas to cereals, but it remains to be seen whether dietary fructose is good or bad for beta cells and human metabolism,” said Björn Tyrberg, Ph.D., adjunct assistant professor in the Diabetes and Obesity Research Center at Sanford-Burnham’s Lake Nona campus in Orlando and senior author of the study.
We’ve made remarkable progress in the war on cancer over the past four decades, but we haven’t won yet. One in two men and one in three women are still expected to get cancer at some point in their lifetimes.
This World Cancer Day, February 4, stand up and do something about it.
Human squamous carcinoma cells with ATF2 (green) located at mitochondria (red) after exposure to genotoxic stress. Nuclei are shown in blue.
The National Cancer Institute (NCI) estimates that as many as one in 51 men and women will be diagnosed with melanoma—the deadliest form of skin cancer—at some point during their lifetimes. A research team led by Ze’ev Ronai, Ph.D. is working to unravel the molecular mechanisms underlying the development and progression of this disease in hopes of improving prevention and treatment strategies. To do this, Ronai’s laboratory has been studying a protein named Activating Transcription Factor 2 (ATF2), which is associated with poor prognosis in melanoma. ATF2 is a two-faced protein—in melanoma cells, it’s oncogenic, or cancer-causing, while in non-malignant types of skin cancers, it acts as a tumor suppressor.
In a paper published February 3 in the journal Cell, the team identified a molecular switch that controls ATF2’s dual functions. This switch is controlled by protein kinase Cɛ (PKCɛ), which disables ATF2’s tumor-suppressing activities, sensitizing cells to chemotherapy; instead, ATF2’s tumor-promoting activity is enhanced. The team also found that high levels of PKCɛ in melanoma are associated with poor prognosis.
Fred Levine, M.D., Ph.D., director of the Sanford Children’s Health Research Center at Sanford-Burnham
In 2008, roughly 14.3 million Americans were taking antipsychotics—typically prescribed for bipolar disorder, schizophrenia, or a number of other behavioral disorders—making them among the most prescribed drugs in the U.S. Almost all of these medications are known to cause metabolic side effects such as obesity and diabetes, leaving patients with a difficult choice between improving their mental health and damaging their physical health. In a paper published January 31 in the journal Molecular Psychiatry, researchers reveal how antipsychotic drugs interfere with normal metabolism by activating a protein called SMAD3, an important part of the transforming growth factor beta (TGFβ) pathway.
The TGFβ pathway is a cellular mechanism that regulates many biological processes, including cell growth, inflammation, and insulin signaling. In this study, all antipsychotics that cause metabolic side effects activated SMAD3, while antipsychotics free from these side effects did not. What’s more, SMAD3 activation by antipsychotics was completely independent from their neurological effects, raising the possibility that antipsychotics could be designed that retain beneficial therapeutic effects in the brain, but lack the negative metabolic side effects.
Atomic model of the NSP-p130Cas complex
Sanford-Burnham has a long history with proteins of the so-called Cas family, particularly one member called p130Cas. For more than a decade, some of our top researchers, including Kristiina Vuori, M.D., Ph.D., Erkki Ruoslahti, M.D., Ph.D., and Elena Pasquale, Ph.D., have studied the biology of these proteins and the role they play in cancer. And they made several groundbreaking findings.
One of these was the co-discovery of a family of novel cell-regulating proteins that interact with Cas proteins, called the NSP family. When Cas and NSP proteins get together, they help a cell migrate or invade surrounding tissues—processes that can be either beneficial, as when immune cells mature, or harmful, as when a cancer cell metastasizes. Furthermore, one particular pair of Cas and NSP proteins were found to cause breast cancer cells to become resistant to anti-estrogen drugs such as tamoxifen, one of the major challenges in fighting this devastating disease.
The new San Diego Skeletal Muscle Research Center will be made up of three core facilities shared by five local institutions.
The National Institutes of Health (NIH) recently awarded a new grant to establish the San Diego Skeletal Muscle Research Center. This new center, led by UC San Diego’s Rick Lieber, Ph.D., Sanford-Burnham’s Mark Mercola, Ph.D., and The Scripps Research Institute’s Velia Fowler, Ph.D., will allow 21 scientists at five different research institutions to combine their expertise and state-of-the-art methods to accelerate research that advances our understanding of skeletal muscles and the diseases that affect them.
Gianna Dragatto, a young patient with a rare disease called Congenital Disorders of Glycosylation
What: Third Annual Sanford-Burnham Rare Disease Day Symposium: Identifying and Treating Genetic Diseases in Children
Where: Sanford-Burnham Medical Research Institute, La Jolla, Calif., Building 12 (map)
When: February 24, 2012 – registration opens at 8:00 a.m. PT, program begins at 9:00 a.m. PT
Keynote speaker: Dr. Eric Green, director of the National Human Genome Research Institute
Program and free registration: click here
Symposium flyer: download PDF
Can’t make it? Submit your genetic disease-related questions for panel discussion to Nick at nburchfi@sanfordburnham.org. The symposium will be recorded and available on Sanford-Burnham’s website shortly after the event.
Sanford-Burnham’s successful series of Rare Disease Day symposia is based on the concept that treatment of rare diseases requires participation and exchange among all stakeholders—scientists, physicians, affected patients and their families, support groups, granting agencies, industry, and philanthropists. This year’s event, organized by Hudson Freeze, Ph.D., will focus on glycosylation-based disorders.
A few highlights:
- Attendance by several children with Congenital Disorders of Glycosylation who are now benefiting from new therapies
- Lunchtime panel discussion for patients and researchers
- Presentation by patient advocacy group
- Discussion of how one rare disorder relates to Parkinson’s disease
Video and media coverage of last year’s event are available here. For more information about Rare Disease Day USA (February 29, 2012), visit the National Organization for Rare Disorders.
Giovanni Paternostro, M.D., Ph.D. and his research group think Nature might have the answer to designing more effective therapies that are less likely to result in resistance: the many-to-many approach.
We all want to find the next miracle drug—especially the one that will cure an ailing loved one. But it can take researchers a long time—decades, sometimes—to discover and develop new medicines. Not only do scientists and doctors hope to create a therapy that works well, but it can’t cause too many side-effects. And even then, after all that time and effort to move the therapy from the lab bench to the patient’s bedside, the drug might stop working after a few months if the patient develops resistance to it.
How can we overcome this final hurdle?
Torrey Pines State Beach, across the street from Sanford-Burnham's La Jolla campus (Photo by Christine Lammer)
As 2011 draws to a close, we look back on our top 11 most popular blog posts published in 2011. Here they are…enjoy!
- How fatty diets cause diabetes
- Witnessing the birth of a new scientific field
- Two-faced nanoparticles and cancer
- Fighting fat with fat
- Crunching the proteome
- Science careers: from postdoc to PI
- Students find summer training opportunities close to home
- How cells sense nutrients and fuel cancer cell growth
- Getting to the root of Alzheimer’s disease
- What is “Disease in a Dish?”
- A new stem cell enters the mix
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.”
insulin-producing beta-cells in a mouse pancreas (Image courtesy of Edward Monosov)
Dr. Barbara Ranscht and her lab are working to better understand how T-cadherin—a protein found on the surface of neurons, muscle, and other cells—regulates communication between cells during development and disease. The best way to go about this is to see what happens when the protein is missing. To do this, her lab developed a mouse model that lacks the protein altogether. Using these animals, Dr. Ranscht’s group has revealed that T-cadherin protects the stressed heart and is necessary for new blood vessel growth in injury models.
One day, Dr. Ranscht found herself discussing possible roles for T-cadherin in metabolism with Sanford-Burnham colleagues Dr. Björn Tyrberg and Dr. Fred Levine. The researchers especially wondered about T-cadherin’s role in the pancreas (Drs. Tyrberg’s and Levine’s organ of expertise).