HSS scientist awarded two NIH grants totaling $6 million

A scientist at Hospital for Special Surgery (HSS), Chitra Dahia, PhD, has received two National Institutes of Health (NIH) grants totaling $6 million for translational research aimed at understanding the root cause of disc degeneration and chronic back pain in order to develop treatment options that do not rely on addictive pain-relieving medications.

This funding will support Dr. Dahia’s Spine Development and Regeneration Lab to study the potential of two important developmental molecules in the reversal of age-related intervertebral disc (IVD) pathologies and in the treatment of chronic back pain.

“Approximately 70 percent of the U.S. population is affected by chronic back pain, negatively impacting longevity and quality of life,” said Dr. Dahia. “There is currently no treatment available for disc degeneration, which is a big concern when you look at the world’s aging population. With the lack of treatment options, people can become dependent on strong pain relievers such as opioids.”

“It is an incredible honor for Dr. Dahia to receive these two NIH grants,” said Lionel B. Ivashkiv, MD, chief scientific officer at HSS. “Being awarded an NIH grant is the highest metric of scientific quality and impact. The application itself is peer-reviewed and quite rigorous.”

Dr. Dahia received the first 5-year grant for $2.8 million from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)/NIH R01 to study the role of the sonic hedgehog (SHH)/Brachyury axis in the maintenance of the postnatal IVD. This work aims to identify the role of Brachyury, a critical developmental molecule first reported in the nucleus pulposus cells of postnatal disc by Dr. Dahia herself in 2009, in the growth and maintenance of the postnatal IVD, how its age-related loss causes disc pathologies and peripheral sensitization and pain, and whether this can be prevented. The study findings will also identify targets to reverse painful disc pathology and help regenerate the disc.

She was then awarded the National Institute of Aging (NIA)/NIH R01 5-year grant for $3.3 million to study the role of developmental signaling pathways in the maintenance of spinal discs. The study is focused on understanding the crosstalk between major developmental signaling pathways interacting with SHH signaling (also first shown by Dr. Dahia in 2009) in temporal regulation of the different components of the IVD and their beneficial effect in maintenance and activation of disc progenitor cells. The research intends to discover if there is a potential for disc regeneration using its own cells, and is being done in collaboration with Todd J. Albert, MD, spine surgeon and surgeon-in-chief emeritus of HSS. Dr. Albert and his team will test Dr. Dahia’s findings in clinical conditions.

“Initially, we found that these crucial developmental molecules are expressed in very young spinal discs, and recently we observed that they decline with age and disc pathology, hence we are now evaluating their function from stages of growth and maturation to aging,” explained Dr. Dahia.

Dr. Dahia has committed her career to developing a full understanding of disc biology as they grow, mature, and age to identify potential avenues for therapeutics. She previously received an NIH grant in 2014 to study how the Wnt/SHH signaling loop controls IVD growth and differentiation. When Dr. Dahia began her research in disc biology over a decade ago, she was one of the first to study the beneficial role of developing molecules in the postnatal spine. Now, this is being adapted in other musculoskeletal research in a broader sense.

According to Dr. Dahia, other researchers have tried to use stem cells to solve these issues, but the cells are unable to survive due to the harsh microenvironment of the disc. “Our lab’s process is unique, as we aim understand the cellular and molecular basis of disc pathology and know how to intersect it, using our unique and novel genetic strategies,” she noted.

Dr. Dahia’s Spine Development and Regeneration Lab at HSS concentrates on understanding the role of key developmental cell signaling pathways and molecules in the development and homeostasis of various musculoskeletal tissues including the IVD, spinal column, growth plate, and tendon. The lab’s primary focus is on IVD development and maintenance and whether developmental pathways and molecules can prevent age-related disc pathologies and associated neurological symptoms or regenerate the degenerated discs.

“These scientific discoveries can directly impact future directions of musculoskeletal research to best improve clinical outcomes,” said Dr. Dahia who noted that HSS research is aimed at enriching the lives of patients suffering from debilitating orthopedic and rheumatic conditions.