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Subburaman Mohan is August’s featured Faculty Member of the Month. A Senior Research Career Scientist at the Veterans Administration (VA), currently the Director of the Musculoskeletal Disease Center at the VA Loma Linda Healthcare Systems and research professor of medicine, orthopedics, biochemistry, and physiology at Loma Linda University in Loma Linda, California. He has been a member or is a current member on the editorial boards of several scientific journals, scientific organizing committees, and grant review panels.

During the past three decades, he has published nearly 400 papers in scientific journals on skeletal biology research, focusing on the discovery of novel genes and evaluation of the functions of genes that are relevant to the acquisition, maintenance, and loss of bone and cartilage using various molecular genetic approaches. This summer he received the Louis V. Avioli Founders Award from American Society for Bone and Mineral Research in recognition of his work.

Many congratulations on receiving the Louis V. Avioli Founders Award. Can you tell us a little bit about your research that led to this award?

I am honoured to receive this year’s Louis V. Avioli Founders Award to mark my contributions to bone and mineral research. I had an exciting start to the field of bone and mineral research by identifying growth factors responsible for the ability of bone to regenerate. We found that that insulin-like growth factors (IGFs) are the most abundant growth factors produced by bone cells. This has been pivotal for subsequent research and led to the current concept on the critical role of IGF system components on growth and maintenance of skeletal system, as well as in the pathogenesis of various bone diseases. Since then, we have discovered that vitamin C could modulate gene transcription by epigenetic mechanisms, which shows that vitamin C acts as a critical mediator on the interface between genome and the environment.

Our research has also provided the first experimental evidence that the thyroid hormone plays a critical role in the continuing regulation of skeletal development and growth. This paradigm shift could have significant clinical implications towards the development of targeted therapies to promote healing of large skeletal defects and non-union fractures – the failure to heal after breaking a bone.

What triggered your interest in research?

Biology has been one of my most favourite subjects during my high school and undergraduate years. My first passion was to become a medical doctor and take care of patients who suffer from the most excruciating illnesses. Since I was not successful in getting into an established medical school, I started pursuing my second passion, which was biological research relevant to clinical diseases. My success in bone research was strongly influenced by my mentor, Professor David Baylink, a world-renowned investigator who has done pioneering work in basic and clinical research related to metabolic bone diseases.

What was your last recommendation and why did you pick it?

I recently selected an article by Tomlinson et al. published in Proceedings of the National Academy of Sciences, which investigated the molecular pathway by which the cells in bone detect and respond to mechanical strain. It is well established that mechanical strain is a key physiological regulator of bone formation and that lack of exercise in elderly subjects is a known risk factor for fractures. For these reasons, we and others have been interested in identifying the signalling pathways by which mechanical strain promotes anabolic response in the skeleton with the understanding that this information will be useful for the development of exercise mimetics – compounds that promote exercise like benefits – to promote bone formation in the elderly. As I noted in my recommendation, the findings of this study that NGF-TrkA signaling contributes to skeletal adaptation to mechanical loads suggest that strategies targeting sensory nerves may be useful in preventing age-related bone loss.

What career advice would you like to pass on to early career researchers?

I would advise early career researchers to pursue discrepancies and not to be afraid to go against the widely-accepted paradigm, if in fact his or her own experimental data is not in support of such a model.  In my own work, our discovery of two novel IGF binding proteins was based on our pursuit to explain the discrepancy that while osteoblasts produced IGFs that are mitogenic, culture medium collected from osteoblasts were inhibitory to IGF actions. The most transformative discoveries are often accidental and unanticipated. Important discoveries occur when researchers follow their curiosity rather than simply pursuing a prescribed research program.