Please join us in welcoming the internationally renowned genomic scientist László Nagy, M.D., Ph.D., to Sanford-Burnham’s Lake Nona campus. Nagy will serve as professor and program director in our Diabetes and Obesity Research Center. He will join us in October to lead a new cross-platform research program that will help accelerate discoveries at our Orlando campus. Nagy is currently professor and head of the Center for Clinical Genomics and Personalized Medicine at the University of Debrecen Medical and Health Science Center in Hungary.
Dr. Nagy will join Sanford-Burnham at Lake Nona in October.
Muscle from normal mice (left) and a mouse model lacking ERRgamma and ERRbeta (right) differ in muscle fiber-type, as indicated by immunofluorescence staining (green = myosin heavey chain 1, blue = myosin heavy chain 2a)
Sanford-Burnham researchers identify microRNAs as the missing link between the two defining features of muscle fitness—fuel-burning and fiber-type switching—providing a potential new target for interventions that boost fitness in people with chronic illness or injury.
Researchers discovered that small pieces of genetic material called microRNAs link the two defining characteristics of fit muscles: the ability to burn sugar and fat and the ability to switch between slow- and fast-twitch muscle fibers. The team used two complementary mouse models—the “marathon mouse” and the “couch potato mouse”—to make this discovery. But what’s more, they also found that active people have higher levels of one of these microRNAs than sedentary people. These findings, published May 8 in The Journal of Clinical Investigation, suggest microRNAs could be targeted for the development of new medical interventions aimed at improving muscle fitness in people with chronic illness or injury.
Left: In fat tissue from a lean mouse, neutrophil elastase and a1-antitrypsin levels are balanced. Right: In fat tissue from an obese mouse, they are imbalanced—neutrophil elastase levels are high (dark staining) and a1-antitrypsin levels are low.
Imbalance between an enzyme called neutrophil elastase and its inhibitor causes inflammation, obesity, insulin resistance, and fatty liver in mice and humans—providing a new therapeutic target for these health conditions
Many recent studies have suggested that obesity is associated with chronic inflammation in fat tissues. In a new study, researchers discovered that an imbalance between an enzyme called neutrophil elastase and its inhibitor causes inflammation, obesity, insulin resistance, and fatty liver disease. This enzyme is produced by white blood cells called neutrophils, which play an important role in the body’s immune defense against bacteria.
The Florida Translational Research Program provides Florida-based scientists with access to Sanford-Burnham's drug-discovery technology and expertise.
We announced today the selection of the first five research organizations that will participate in the Florida Translational Research Program (FTRP) to advance drug discovery in the state. The projects focus on cancer, diabetes, and obesity, and are led by scientists from the University of Central Florida, the University of Florida, the University of Miami, Scripps Florida, and a team of our own Lake Nona scientists. The Florida Department of Health and Sanford-Burnham established the FTRP as a competitive grant program that provides funding for collaborative drug discovery projects. The overall goal of the program is to translate research discoveries made in Florida laboratories into the medicines of tomorrow.
3D structure of HNF-4α, a protein mutated in MODY1, a rare, inherited form of diabetes, reveals new pockets that could be targeted with therapeutic drugs
Researchers have determined the complete three-dimensional structure of a protein called HNF-4α. HNF-4α controls gene expression in the liver and pancreas, switching genes on or off as needed. People with mature onset diabetes of the young (MODY1), a rare form of the disease, have inherited mutations in the HNF-4α protein. This first-ever look at HNF-4α’s full structure, published today in Nature, uncovers new information about how it functions. The study also reveals new pockets in the protein that could be targeted with therapeutic drugs aimed at alleviating MODY1.
Cardiac fibrosis (shown in purple), a hallmark of heart disease, is clearly increased in fruit flies on a high-sugar diet (right), as compared to flies on a normal diet (left).
First fruit fly model of diet-induced type 2 diabetes shows how high-sugar diet affects the heart and reveals new therapeutic opportunities
Regularly consuming sucrose—the type of sugar found in many sweetened beverages—increases a person’s risk of heart disease. In a study published January 10 in the journal PLOS Genetics, researchers at Sanford-Burnham Medical Research Institute and Mount Sinai School of Medicine used fruit flies, a well-established model for human health and disease, to determine exactly how sucrose affects heart function. In addition, the researchers discovered that blocking this cellular mechanism prevents sucrose-related heart problems.
“Our study reveals a number of specific sugar-processing enzymes that could be targeted with therapies aimed at reducing sucrose’s unhealthy effects on the heart,” said Karen Ocorr, Ph.D., research assistant professor at Sanford-Burnham and the study’s corresponding author.
Left: healthy beta cells. Right: type 2 diabetic beta cells lose their glucose-sensing capability as glucose transporters (green) are internalized due to environmental disturbances brought about by fat and obesity.
A new computational model of sugar transport in the pancreas reveals a metabolic “tipping point” in type 2 diabetes—a discovery that may form the basis for new efforts to prevent and treat the disease.
Changes in cellular metabolism play a bigger role in the development of type 2 diabetes than previously thought—perhaps an even larger part than genetic predisposition plays in the disease. That’s what Sanford-Burnham and UC Santa Barbara researchers concluded in a study published recently in the journal PLOS ONE. The team, including Jamey Marth, Ph.D., developed a computational model to better understand the underlying causes and progression of type 2 diabetes. The model revealed a metabolic “tipping point” that, when crossed, prevents the pancreas from adequately sensing blood sugar and secreting insulin. The team expects the discovery will form the basis for new efforts to prevent and treat type 2 diabetes.
Fred Levine, M.D., Ph.D., director of the Sanford Children’s Health Research Center at Sanford-Burnham
How antipsychotics cause side effects such as obesity and diabetes
Originally published January 31, 2012
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.
A moment from the Art in Science/Science in Art panel. L to R: Dr. Thomas Albright, The Salk Institute for Biological Studies; Dr. Pamela Itkin-Ansari, Sanford-Burnham Medical Research Institute; Dr. Santiago Horgan, UCSD School of Medicine.
Science and art have a lot in common. That was the clear conclusion drawn by a panel of experts at the world-renowned La Jolla Playhouse on November 11, at an event titled The Art in Science/The Science in Art. Collaboration, the willingness to take risks, and the making of what one panelist called “intuitive leaps” all rose to the fore as shared traits. Although perhaps the most significant thing the two disciplines have in common, they realized, is the ongoing need for funding.
“You hear a lot about patrons of the arts,” remarked Sanford-Burnham adjunct faculty member Dr. Pamela Itkin-Ansari. “I think we also need more patrons of science.” Based on their enthusiastic applause, the audience agreed.
Symposium attendees await the announcement of Best Talk and Best Poster awards (Photo by Karolina Kucharova)
Each year, the Sanford-Burnham Science Network, our organization of postdoctoral researchers and graduate students, holds a symposium for young scientists to practice presenting their work and gain valuable feedback from their peers and our faculty members. This year, the La Jolla group’s event was held at the Sanford Consortium for Regenerative Medicine.
Here are five random things we learned last week at the 11th annual symposium:
Congratulations to John B. Gurdon and Shinya Yamanaka on winning the 2012 Nobel Prize in Physiology or Medicine! They received the award today for their “discovery that mature cells can be reprogrammed to become pluripotent.” In other words, these scientists figured out how to turn a normal adult cell, such as a skin cell, into a stem cell that has the potential to become any other type of cell in the body. Read below to learn more about stem cells and how they are revolutionizing medical research.
What are stem cells?
Stem cells are special because each is like a blank slate. Once it’s given the proper instruction, a stem cell can specialize and become any type of cell in the body—brain, heart, muscle, and more. Stem cells also have the ability to reproduce themselves indefinitely, renewing the supply.
Are there different types of stem cells?
Embryonic stem cells only exist during an organism’s development, when it is an embryo. These cells are pluripotent, meaning they have the capacity to become any cell type in the body.
Adult stem cells exist in fully developed organisms. They are more limited than embryonic stem cells—they are multipotent rather than pluripotent. These stem cells usually can only become a few types of specialized cells, based on the tissue from which they originate.
Induced pluripotent stem cells (iPSCs) are pluripotent, much like embryonic stem cells. iPSCs are produced in the laboratory by genetically reprogramming any adult cell, such as a skin cell.