Rejuvenation

Functional decline of tissues and organs and increased risk of complications are key characteristics of ageing. “Rejuvenating” interventions have been touted as a potential strategy to address age-associated complications and promote “healthy” aging.  Various approaches such as reprogramming, heterochronic parabiosis, pharmacological drugs to “restore” cellular and molecular regenerative landscapes, and senolytics to ablate senescent cells have been currently explored as “age-delaying” interventions. We are interested in understanding age-related changes in musculoskeletal tissues (bone and cartilage) such as compromised fracture healing and osteoarthritis. Our research also focuses on developing technologies to address this age-associated tissue degeneration and compromised healing. Another area we are interested is neurodegeneration. Neurodegeneration and associated diseases are common with ageing. Neuroinflammation is a key pathologic hallmark of many neurologic disorders, especially neurodegenerative conditions such as Alzheimer’s disease and Alzheimer’s disease-related dementias. We are interested in understanding the reciprocal interactions between the systemic milieu and the brain, including the blood-brain barrier, on neuroinflammation especially following peripheral injuries. What is the role of cellular resilience and/or plasticity on age-associated complications? Another aspect of ageing is tissue degeneration, which is often associated with pain. Pain is not only associated with ageing; it is a debilitating symptom of many diseases and injuries and experienced by all and across all age groups. While acute pain is a sensation generated to alert to a possible injury, chronic pain persists beyond the regression of the disease or injury and is considered as a disease itself. In fact, pain is the most common reason for seeking medical care and is a major contributor to the opioid crisis. Through a number of ex vivo and in vivo models, we are studying pain sensation and sensitization and also developing technologies to mitigate pain, including post-operative pain.

D Katrekar, G Chen, D Meluzzi, A Ganesh, A Worlikar, Y-R Shih, S Varghese, and P Mali. "In vivo RNA editing of point mutations via RNA-guided adenosine deaminases.Nat Methods 16, no. 3 (2019): 239-242.

M Liu, M Nakasaki, Y-RV Shih, and S Varghese. "Effect of age on biomaterial-mediated in situ bone tissue regeneration.Acta Biomater 78 (2018): 329-340.