Metabolic Signaling

Sepideh Khorasanizadeh & chromosome unraveling

by Heather Buschman, Ph.D. on August 24, 2010 at 2:20 pm | 1 comment

Each of our cells contains a lot of DNA. So much DNA, in fact, that it has to be elaborately condensed and organized into chromosomes, which are then packed into the cell’s nucleus. If completely unraveled, the genetic material from just one of our 46 chromosomes would stretch out to 1.5 centimeters – 10,000 times the length of the packed chromosome.To condense all of this genetic material, long strands of DNA are tightly wound around proteins called histones. All this packing, however, can present a problem when our cellular machinery needs to access our DNA to read genes and produce proteins. As a result, chromosome packing is dynamic – some areas stay tightly wound while others are looser. Just how accessible a particular region is can vary, depending on the tissue type, stage of development, disease state and other factors.

Dr. Sepideh Khorasanizadeh, one of Sanford-Burnham’s newest faculty members in Lake Nona, Florida, studies the cellular signals that influence chromosome packing to turn genes on and off. While much is known about how cells receive signals from the environment and carry those signals across into the cytoplasm, what happens when they reach the nucleus remains a mystery.

A balance of fat and sugar

by Heather Buschman, Ph.D. on August 17, 2010 at 3:57 pm | 1 comment

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Diabetes results from a lack of functioning insulin, a hormone that stimulates cells to take up glucose (a type of sugar) from the bloodstream. Cells need glucose as fuel to produce energy. Type 1 diabetics lack insulin because their immune systems destroy the pancreatic cells that produce it. In type 2 diabetics, cells no longer respond properly to insulin. Either way, without sugar that can be converted to energy, cells starve and glucose levels build up in the blood, which can lead to life-threatening complications such as heart disease.

“When mice – or people – eat too much fat, they become obese and increasingly resistant to insulin, an early sign of type 2 diabetes,” explained Dr. Julio Ayala, assistant professor at Sanford-Burnham’s Lake Nona campus.

“Fat” man

by Josh Baxt on August 13, 2010 at 12:21 pm | 4 Comments

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Dr. Philip Wood is immersed in fat: fat metabolism, fatty acids, fat signaling, fatty liver disease. Dr. Wood, a professor in the Metabolic Signaling and Disease program at Sanford-Burnham’s Lake Nona campus, is trying to unravel the consequences of too much fat.

“I’m interested in how the body reacts to excess fat and how fat metabolism and the genetics of fat metabolism play a role in insulin resistance and fatty liver disease,” says Dr. Wood.

Given that recent statistics show a third of Americans are obese, the research being done by Dr. Wood and others could have a profound impact on the nation’s health. One key focus is the underlying genetics that make certain people susceptible to disease.

Brown fat: not just for babies and bears

by Heather Buschman, Ph.D. on July 29, 2010 at 8:41 am | 5 Comments

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Brown fat cells

Sanford-Burnham’s Dr. Sheila Collins recently returned from Stockholm, where she attended a meeting on brown fat (also called brown adipose tissue) and obesity, held in conjunction with the XI International Congress on Obesity. Brown fat, which helps generate heat, was historically thought to be limited to small mammals such as rodents, newborns of larger mammals (including humans), and hibernators – in order for them to stay warm. Scientists used to think that brown fat disappeared after infancy, but recent advances in imaging technology led to a rediscovery of brown fat in adult humans. This meeting brought together scientists studying the basic biology of brown fat tissue and its possible role in adults in order to figure out how all this information can be applied to fight obesity.

A mission to teach

by Josh Baxt on July 7, 2010 at 1:43 pm | 1 comment

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This summer, a group of college students, high school seniors and a science teacher are coming to Sanford-Burnham at Lake Nonato learn about biomedical research and gain hands-on laboratory experience.Russell Fullerton, who is studying biochemistry at Cornell University, wants to go to medical school. He is working in Dr. Philip Wood’s laboratory, helping to develop ways to identify mouse genotypes that model human disease.

“I worked in a Cornell lab last summer and really enjoyed it,” says Fullerton. “I am particularly interested in the scientific focus in Dr. Wood’s lab and the opportunity to work with mouse models. Up until now, I’ve only worked with bacteria.”

But Fullerton’s scientific journey is only beginning. He is also working with lab scientist Alvin Almodovar to analyze variations in DNA sequences that can affect how humans respond to pathogens, chemicals, drugs and vaccines. Called single-nucleotide polymorphisms, these markers help us understand how genetic variation can influence a person’s susceptibility to disease.

Food, energy, and orexin

by Josh Baxt on July 2, 2010 at 2:47 pm | 8 Comments

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Ever wonder why you feel sleepy after a heavy meal and why it is difficult to catch some Zs when you’re hungry? It’s because our blood glucose levels directly control the amount of a hormone called orexin, which influences hunger and sleep/wake cycles. High glucose after a meal reduces orexin levels and the activity of orexin-producing neurons, making us feel sluggish. Plunging glucose levels following overnight fasting elevates orexin levels, which wakes us up to seek food. In other words, soaring orexin levels trigger wakefulness, vigilance and hunger; reduced levels induce inactivity and somnolence.“Regulation of hunger and consciousness appear to be intimately tied to our metabolic state,” says Dr. Dev Sikder, an assistant professor in the Metabolic Signaling and Disease program at Sanford-Burnham’s Lake Nona campus . “Consistent with this theory, the cyclic waxing and waning of orexin levels appears to be perturbed in metabolic disorders such as type 2 diabetes, obesity and even cancer. These disorders are also a consequence of physical inactivity and sleep/wake disturbances, which are directly influenced by orexin. Indeed, several epidemiological studies have reported a correlation between lower orexin levels and a higher incidence of obesity and type 2 diabetes.”

Diabetes meeting adds a human element to research

by Heather Buschman, Ph.D. on July 1, 2010 at 3:46 pm | 0 Comments

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This week in Orlando, Fla., the American Diabetes Association (ADA) gathered doctors and scientists from all over the world to drive its mission “to prevent and cure diabetes and to improve the lives of all people affected by diabetes.” Many of Sanford-Burnham’s Lake Nona researchers attended the ADA’s annual meeting, including Dr. Sheila Collins, professor in the Diabetes and Obesity Research Center, and post-doctoral researchers Dr. Zhenji Gan and Dr. Rita Luther.“By bringing together scientists and clinical doctors, large interdisciplinary meetings like this help us to think more broadly about how our research impacts diabetes patients,” said Dr. Collins, whose work has been funded by the ADA in the past. “Clinical doctors attending the basic research sessions will sometimes ask a question that brings a different perspective to those of us working in the lab.”

Dr. Luther, who studies inflammation in Dr. Philip Wood’s laboratory, agreed, saying that the ADA meeting was very different from other scientific conferences she has attended. “Clinical lectures and chance meetings with nurses and doctors were eye-opening,” she commented. “Learning about what patients need provides a human element to research.”

The Promise of Chemical Genomics

by Josh Baxt on June 22, 2010 at 2:52 pm | 16 Comments

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With the completion of the Human Genome Project in 2003, scientists have a basic blueprint of our DNAand the genes it contains. While the project answered many questions, it also left many unanswered. How and why are genes turned on and off? What proteins do specific genes produce? What do those proteins do, and how does their activity affect our health?The Conrad Prebys Center for Chemical Genomics (Prebys Center) seeks to answer these and other questions by finding small molecule chemical compounds that selectively bind to a specific protein and turn it on or off. Small molecules are valuable because they help scientists determine a protein’s function in a cell. These are the first steps toward understanding how a dysfunctional protein can cause disease—important knowledge that can lead to new treatments.

The journey to good nutrition

by Josh Baxt on June 7, 2010 at 3:55 pm | 0 Comments

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We all, at some point, have come to the realization that we can eat better. That moment may have arrived during a visit to the doctor, a morning weigh-in or a second plate at Thanksgiving. Regardless of the occasion, we have learned that how we eat dramatically impacts our health. The challenge is to translate that fact into sound nutritional choices. To help with this process, Sanford-Burnham recently hosted a panel discussion, entitled Nutrition for Life, to provide new insights into how our diets can contribute to good health.

Moderated by Sanford-Burnham professor and CEO Dr. John Reed, the panel featured author John Robbins, Chef Jeff Jackson and Sanford-Burnham researcher Dr. Timothy Osborne. Together, the speakers shared their evolving understanding of how best to eat well.

The skinny on fat resistance

by Heather Buschman, Ph.D. on June 3, 2010 at 8:31 am | 1 comment

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Dr. Philip Wood, professor in Sanford-Burnham’s Diabetes and Obesity Research Center at Lake Nona, Florida, co-authored a study showing that obesity-resistant mice could be genetically engineered by deleting an enzyme that helps break down fatty acids. The study, which appeared May 5 in the journal Cell Metabolism, was co-led by Dr. Wood and Dr. Gerald Shulman of the Howard Hughes Medical Institute and Yale University.

In the study, mice lacking the gene – called VLCAD – were fed a high-fat diet. Since VLCAD is necessary for normal fatty acid metabolism and the production of cellular energy, the scientists figured that disrupting the gene’s function would inhibit metabolism and lead to weight gain and other ailments. However, instead of packing on extra fat, the mice were actually protected from obesity and insulin resistance (an early stage of type 2 diabetes). The researchers think that VLCAD deficiency triggers a back-up mechanism that acts like an emergency generator, compensating for the loss of the enzyme.

“This study illustrates the power of a genetic mouse model to tease apart different components of the fat burning process and insulin resistance, a common side effect of obesity,” Dr. Wood explained. “By inactivating this one step in fat burning, we activated two different drug targets currently used to treat problems of excess fat in human patients.”

Dr. Wood was also interviewed in a recent story about obesity by WJRT-TV, the ABC affiliate in Flint, Michigan.

Diabetes and its Consequences

by Josh Baxt on June 2, 2010 at 10:19 am | 4 Comments

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Insulin is produced in the pancreas by beta cells, which measure glucose (the main source of energy from food) in the blood and secrete insulin to control glucose concentrations. Insulin acts as a key, binding to receptors (locks) expressed by all cells and telling them to let glucose inside.In type 1 diabetes, beta cells are destroyed by the body’s own immune system. White blood cells that ordinarily protect us from bacteria and viruses mistakenly recognize beta cells as foreign and destroy them, reducing or eliminating insulin production.

In type 2 diabetes, the problem is with the insulin receptor—the lock that allows glucose to enter. For reasons that are not clear, the receptor mechanism does not work properly, even when insulin is present. The body responds by producing more insulin. While that works for a time, it overworks the beta cells, which ultimately fail and die.

High circulating glucose levels damage cells. Because glucose moves primarily through blood, the cells lining blood vessels are the most severely hurt. These consequences extend to virtually every organ in the body. Diabetes is a leading cause of blindness, kidney disease, amputation, heart disease and many other conditions.

Researchers receive $3.5 million in NIH grants

by Josh Baxt on May 5, 2010 at 11:59 am | 0 Comments

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Two researchers at Sanford-Burnham at Lake Nona have received grants to study heart disease and how fat cells function in the body.Lake Nona Scientific Director Dr. Daniel Kelly will be collaborating with Dr. Deborah M. Muoio of the Stedman Center at Duke University to investigate the metabolic basis of heart failure. The $2.9 million, four-year grant will help researchers better understand the mechanisms that cause heart disease and identify potential drug targets for heart failure.

Dr. Sheila Collins received a $525,000, two-year grant to study how beta-adrenergic receptors on fat cells regulate growth. This research will enhance our understanding of how fat cells contribute to metabolic syndrome and could also lead to new drug targets.

Experiments from outer space

by Althia Davis on April 23, 2010 at 9:52 pm | 0 Comments

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Professor and astronaut Millie Hughes-Fulford visited Sanford-Burnham Medical Research Institute at Lake Nona today. She’s been eagerly awaiting this day since Shuttle Discovery returned from space on Tuesday with her experiment on board. Dr. Hughes-Fulford sent her experiment on the 15-day space journey to test how memory cells survive in space and how T-cells are activated.

There’s more to fat

by Josh Baxt on April 20, 2010 at 3:38 pm | 3 Comments

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Sheila Collins, Ph.D., recently joined Sanford-Burnham at Lake Nona as a professor in the Metabolic Signaling and Disease program. Her lab is interested in fat metabolism. Until the mid-1990s, adipose (fat) tissue had been largely considered an inert storage depot for excess metabolic fuel, much like a savings bank. There is now a better understanding of how fat cells secrete key hormones that play help regulate body weight and insulin sensitivity.

Sepideh Khorasanizadeh & chromosome unraveling

A balance of fat and sugar

“Fat” man

Brown fat: not just for babies and bears

A mission to teach

Food, energy, and orexin

Diabetes meeting adds a human element to research

The Promise of Chemical Genomics

The journey to good nutrition

The skinny on fat resistance

Diabetes and its Consequences

Researchers receive $3.5 million in NIH grants

Experiments from outer space

There’s more to fat

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