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Breakthrough reveals first ever complete structure of a nuclear hormone receptor on human DNA

For decades, scientists have been studying nuclear hormone receptors to gain a better understanding of how they turn genes on and off throughout the body and how they function as key drug targets for a number of diseases, such as diabetes, breast cancer, osteoporosis and high cholesterol. A new UVA Health System study, led by Fraydoon Rastinejad, Ph.D., professor of pharmacology and director of the UVA Center for Molecular Design and published in the October 29 issue of Nature, reveals the first ever complete structure of a nuclear hormone receptor on human DNA – a discovery that now clears a new path for scientists to design more effective drugs with fewer associated health risks. “Dr. Rastinejad’s findings fundamentally change the way people all over the world will study how nuclear hormone receptors work and introduces a new platform for designing better drugs,” says Jim Garrison, Ph.D., professor of pharmacology at UVA Health System. Nuclear hormone receptors, including the peroxisome proliferator-activated receptors (PPARs), are proteins that sit on the surface of cells and bind to specific hormones such as estrogen, progesterone and thyroid hormone. Once the receptor binds to its hormone and its DNA regulatory element, it can cause a number of alterations in the cell, switching genes on and off. These switches control the continual regulation of the metabolic system and reproductive tissues, as well as the development and differentiation of skin, bone and behavioral centers in the brain. “PPARs are widely studied because they regulate the genes that produce fat cells, glucose, insulin, lipids and metabolism,” says Dr. Rastinejad. “That’s what makes them such good drug targets for diseases like diabetes. We can design drugs more rationally to bind to the PPAR nuclear receptor complex to help regulate these functions in the body.” A number of diabetes drugs, called insulin sensitizers, have been developed based on that knowledge, but now that scientists have a clear view into how these receptors bind and what shape they take the door is wide open for the development of better drugs. "After 40 years of nuclear receptor research, we finally can view the first full and complete structure of a nuclear receptor, thanks to Dr. Rastinejad’s break-though achievement,” says Bert W. O’Malley, Ph.D., professor and chairman, Department of Molecular and Cellular Biology at Baylor College of Medicine who is widely considered a top expert in the field.

17 Nov 2008

Community-based physical activity interventions found to be cost-effective

Community-based physical activity interventions designed to promote more active lifestyles among adults are cost-effective in reducing heart disease, stroke, colorectal and breast cancers, and type 2 diabetes, according to a study by the Centers for Disease Control and Prevention, with support from the Robert Wood Johnson Foundation.

16 Nov 2008

Rosuvastatin trial shows dramatic reduction in hidden heart disease

A Harvard-led study shows that the risk of heart attack and stroke among subjects with "silent heart disease" - and normal cholesterol levels - can be dramatically reduced by the use of an already widely prescribed class of drugs.

13 Nov 2008

Staying active may lower health risks for large, retired athletes

The larger body size of professional football players doesn't increase risk of cardiovascular disease or atherosclerosis after they retire, according to research presented at the American Heart Association's Scientific Sessions 2008.

12 Nov 2008

U.S. health trend in heart disease is not going down as expected

The positive U.S. health trend documented over the past 30 years of reduction in risk for heart disease is not as strong as is widely perceived - and, in fact, the trend has flattened, according to a new analysis of national data by Mayo Clinic.

11 Nov 2008

Sex hormones may affect atherosclerosis

Naturally produced sex hormones may influence the risk and progression of atherosclerosis, or hardening of the arteries, Johns Hopkins researchers report in a recent study.

11 Nov 2008

Obesity raises levels of hormone leptin

Obese people who don't have high cholesterol or diabetes might think they're healthy - despite the extra pounds.

11 Nov 2008

Obstructive sleep apnea may be risk factor for sudden cardiac death

After studying the sleep characteristics of nearly 11,000 adults in an overnight sleep laboratory, Mayo Clinic researchers suggest that obstructive sleep apnea (OSA) - and, in particular, the low nighttime oxygen saturation of the blood it causes - may be a risk factor for sudden cardiac death (SCD).

11 Nov 2008

Obstructive sleep apnea and sudden cardiac death

10 Nov 2008

Low levels of potassium in diet linked to high blood pressure

As a risk factor for high blood pressure, low levels of potassium in the diet may be as important as high levels of sodium - especially among African Americans, according to research being presented at the American Society of Nephrology's 41st Annual Meeting and Scientific Exposition in Philadelphia, Pennsylvania.

10 Nov 2008

Prevalence of metabolic syndrome and associated risk factors in Illinois

Adopting daily exercise sessions and a calcium-rich diet could reduce the risk of a group of health risk factors called the metabolic syndrome, finds a new study of Illinois adults.

7 Nov 2008

GlaxoSmithKline believes there is no liver safety issue with Avandia (rosiglitazone maleate)

GlaxoSmithKline today issued the following response to a petition filed by Public Citizen to the U.S. Food and Drug Administration (FDA) on Avandia (rosiglitazone maleate), a highly effective therapy for treating type 2 diabetes when used in the appropriate patient population.

31 Oct 2008

Mylan confirms generic Lescol patent challenge

Mylan Inc. has confirmed that the company and its subsidiary, Mylan Pharmaceuticals Inc., have been sued by Novartis in connection with Fluvastatin Capsules USP, 20 mg (base) and 40 mg (base), the generic version of Novartis' Lescol(R) Capsules.

22 Oct 2008

Statin-induced muscle disorders are focus of $2.5 million in grants from NIH

Approximately 200,000 of the 38 million people in the U.S. who take statins to treat high cholesterol may develop life-threatening muscle disease.

2 Oct 2008

Cholesterol research, begun in the 'Little Skate,' Garners Award

New research on the way the body processes cholesterol has earned a scientist at the University of Rochester Medical Center one of the highest honors in the field.

2 Oct 2008

Existing anti-obesity drugs may be effective against flu, hepatitis and HIV

Viruses dramatically increase cellular metabolism, and existing anti-obesity drugs may represent a new way to block these metabolic changes and inhibit viral infection, according to a study published today in the journal Nature Biotechnology.

29 Sep 2008

Gene variant boosts risk of fatty liver disease

Researchers at UT Southwestern Medical Center have found that individuals who carry a specific form of the gene PNPLA3 have more fat in their livers and a greater risk of developing liver inflammation.

25 Sep 2008

Oversize waistlines are a potent risk factor for heart disease in women

A heart expert at Johns Hopkins is calling for all women with a waistline measuring more than 35 inches to get an annual check-up and detailed risk assessment for heart problems because excess abdominal fat, even in the mildly obese and overweight, leads more than a third of women to underestimate their lifetime risk of having a heart attack, stroke or chest pain (angina).

24 Sep 2008

Experts say thousands at risk for heart disease go unchecked

Australian experts say thousands at risk for heart disease go unchecked and are not getting the drugs which protect them.

15 Sep 2008

Depressed dialysis patients more likely to be hospitalized or die, researcher finds

Dialysis patients diagnosed with depression are nearly twice as likely to be hospitalized or die within a year than those who are not depressed, a UT Southwestern Medical Center researcher has found.

14 Sep 2008