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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

CAPHOSOL shown to benefit cancer patients undergoing chemotherapy and radiation therapy

New data show that CAPHOSOL, an advanced electrolyte solution, results in low rates of oral mucositis and pain in patients with head and neck (HN) cancer who are undergoing chemotherapy and radiation therapy.

17 Nov 2008

Discovery of new mechanism that regulates formation of blood vessels

Researchers in one of the external groups of the Instituto Gulbenkian de Ciencia (IGC), in Portugal, have discovered a novel mechanism which regulates the process whereby new blood vessels are formed and wounds heal, including chronic wounds, such as those found in diabetic patients and those suffering from morbid obesity.

17 Nov 2008

Proton therapy may reduce serious side effect of lung cancer treatment

Patients with locally advanced lung cancer who receive chemotherapy and proton therapy, a specialized form a radiation therapy only available in a few centers in the United States, have fewer instances of a serious side effect called bone marrow toxicity than patients who receive chemotherapy and another type of radiation therapy called intensity modulated radiation therapy (IMRT), according to a study presented at the 2008 Chicago Multidisciplinary Symposium in Thoracic Oncology, sponsored by ASTRO, ASCO, IASLC and the University of Chicago.

16 Nov 2008

Higher levels of blood phosphate may be a previously unidentified and modifiable cardiovascular risk factor

Healthy adults with higher levels of phosphate in the blood are more likely to have increased levels of calcium in the coronary arteries-a key indicator of atherosclerosis and future cardiovascular disease risk, reports a study in the February 2009 issue of the Journal of the American Society of Nephrology (JASN).

16 Nov 2008

Researchers evaluate root canals versus extraction and dental implants

A new study addresses the growing controversy among dental health professionals regarding the best course of treatment when evaluating between a root canal or dental implant procedure.

16 Nov 2008

Breast and prostate cancer treatment may result in bone loss

A new cross-Canada study has found that breast and prostate cancer treatment can foster bone loss.

16 Nov 2008

Osteoporosis drugs may prevent future bone growth

Patients who start and eventually stop regimens of a common class of osteoporosis drugs called bisphosphonates may be unable to benefit from parathyroid hormone (PTH), which can rebuild bone mass lost due to advanced stage osteoporosis. PTH has been proven to increase the volume and strength of the honeycomb-like bone infrastructure, the inner mesh that begins to diminish in old age.

13 Nov 2008

Swiss approval for Zevtera in treatment of complicated skin and soft tissue infections

Swissmedic, the Swiss agency for therapeutic products, has approved Zevtera (ceftobiprole medocaril) for the treatment of complicated skin and soft tissue infections, including diabetic foot infections which have not spread to the bone.

13 Nov 2008

A new method to control bleeding in hemophilia

Investigators at Children's Research Institute, BloodCenter of Wisconsin's Blood Research Institute and the Medical College of Wisconsin have discovered a new way to help the blood clot by having the missing clotting factor packaged in the patient's own platelets.

13 Nov 2008

Prime Ministers and Presidents must be more open about their health status

Anyone who runs for Prime Minister or President should have an independent health examination to ensure their ability to govern, argues a doctor on bmj.com today.

12 Nov 2008

Intraspinal implant of mesenchymal stem cells may not heal the demyelinated spinal cord

Multiple sclerosis is a disease caused by the loss of the myelinated sheath surrounding the nerve fibers of the spinal cord.

12 Nov 2008

Osteoporosis care at risk in the U.S.

Cuts to Medicare reimbursement of DXA undermine efforts to properly diagnose and treat osteoporosis and diminish quality of patient care.

12 Nov 2008

Stem cells from umbilical cord blood may help build new heart valves

Children with heart defects may someday receive perfectly-matched new heart valves built using stem cells from their umbilical cord blood, according to research presented at the American Heart Association's Scientific Sessions 2008.

11 Nov 2008

Epstein-Barr virus linked to inflammatory diseases of the mouth

Researchers at Oregon Health & Science University's School of Dentistry have found that a significant percentage of dental patients with the inflammatory diseases irreversible pulpitis and apical periodontitis also have the Epstein-Barr virus.

11 Nov 2008

New technology to control the motion of bacteria that produce cellulose - biomaterial and medical implant potential

Two Virginia Tech engineers have put bacteria to work as tiny weavers of biomaterials and medical implants.

11 Nov 2008

Daily rhythms in endothelial cells may explain why heart attacks occur most often in early morning hours

It's not just the stress of going to work. Daily rhythms in the activity of cells that line blood vessels may help explain why heart attacks and strokes occur most often in early morning hours, researchers from Emory University School of Medicine have found.

11 Nov 2008