Samantha Chin
Program: Molecular Cell Biology
Current advisor: Silvia Jansen, PhD
Undergraduate university: Brandeis University
Research summary
Osteoporosis is the most common bone disease in the world that classically affects the elderly, but now, more generally describes a condition of low bone mass and increased bone fragility that arises in children as well as adults. A diagnosis of osteoporosis in children is particularly problematic as this period represents a time of critical bone development that also determines bone health later in life. The mainstay of osteoporosis treatment is targeted at relieving imbalances in bone resorption and bone formation by curbing bone-resorption. This approach, however, is plagued by undesirable side-effects and concerns regarding long-term efficacy, particularly in the treatment of affected children. As such, alternative strategies and therapeutic targets are paramount to the effective treatment of osteoporotic adults as well as children. Plastin-3 (PLS3) is a calcium-sensitive actin-bundling protein that has recently emerged as a promising new regulator of bone health. Genetic analysis of patients presenting with X-linked childhood-onset osteoporosis revealed a diverse array of more than 20 pathogenic mutations in the PLS3 gene. Affected children present with low bone mineral density as well as recurrent fractures as early as 2 years of age; however, their clinical presentation provides little insight into the pathophysiology underlying their disease state. This work will fill major gaps in our understanding of how PLS3 mutation leads to the development of childhood-onset osteoporosis by elucidating how PLS3 mechanistically contributes to osteoblast differentiation and mineralization in vitro as well as in vivo.
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Graduate publications
Chin SM, Hatano T, Sivashanmugam L, Suchenko A, Kashina AS, Balasubramanian MK, Jansen S. 2023 N-terminal acetylation and arginylation of actin determines the architecture and assembly rate of linear and branched actin networks. J Biol Chem, 298(11):102518.
Chin SM, Unnold-Cofre C, Naismith T, Jansen S. 2023 The actin-bundling protein, PLS3, is part of the mechanoresponsive machinery that regulates osteoblast mineralization. Front Cell Dev Biol, 11():1141738..