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Interview with Edward Hsiao MD PhD of UCSF

by Julia Moore, Drake HS

How did you become interested in musculoskeletal disorders?
I’ve always been interested in the skeleton. Although we typically think of bones as being solid and unchanging, they undergo a variety of very significant events throughout our lifetime, including growing and repairing after injury. In addition, bones are central to us as a living organism. They provide structure to our bodies, protect soft or vital organs, allow us to move efficiently, and provides bone marrow space for blood formation. We now know that many medically important diseases including osteoporosis, atherosclerosis, and heterotopic bone ossification are all a result of problems affecting normal bone formation.

How are we currently treating different types of musculoskeletal disorders?
Since we don’t  understand how many musculoskeletal disorders develop, our ability to prevent them is pretty limited. Treatments for established disease are also very rudimentary and mostly symptomatic. For example, many inherited diseases of the bone can only be treated by surgery to remove the affected bone. In some cases, we can use metal implants or joint replacement, but these have a relatively short lifespan. Even common diseases, such as osteoporosis or arthritis, have only limited medical treatments.

How do you do your research?
My research is driven by a desire to understand how hormones and genetics control human skeletal growth. Since getting samples of diseased tissues from patients is often difficult, I use a variety of model systems to study skeletal disease. This includes mouse models where I can control hormone signals, and human stem cells created from patients with genetic skeletal diseases (human induced pluripotent stem cells). Together, these models are helping us understand what causes disease and how we can develop new treatments.

What are artificial hormones and how are they advancing research and treatment?
Nature uses hormones as a way to communicate between different parts of the body. One major class of hormone molecules is called G-protein coupled receptors (GPCRs). Since there are over 500 GPCRs in the human genome, figuring out what each individual receptor does is a huge challenge. Our strategy uses a synthetic receptor that only responds to a synthetic drug. This system acts like an artificial hormone – if we add the drug, we can turn the system on; if we take away the drug, we can turn it off. This system allows us to “mimic” a normal hormone system and control that pathway using our drug. This model has proven useful for studying hormone signaling in complex organ systems, including cardiac disease, the brain, and now bone.

What do you think is the future of treatment and prevention of musculoskeletal disorders?
I think that developing robust prevention strategies is important. We also need to develop better combinations of surgical and medical management that have fewer side effects. Much of this can be gained by a better understanding of what happens in normal growth and how those mechanisms go wrong in disease. Finally, I believe that human stem cells provide a valuable new tool in this effort by allowing us to study lab-derived human tissues directly. These stem cells are already providing insights into some rare and dramatic bone diseases. We hope to be able to extend our findings to more common disorders.

Edward Hsiao will be speaking at Terra Linda High School in Room 207 on
Wednesday February 29th at 7:30-8:30pm

Written by: Julia Moore 

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