Assistant Professor of Orthopedics
Our research focuses on the role of endoplasmic reticulum (ER) homeostasis in context of skeletal health. Osteoblasts are bone matrix synthesizing cells and rely on their extensive ER for secretion of proteins. Accumulation of misfolded proteins in the ER results in ER stress and activates the Unfolded Protein Response (UPR) to restore homeostasis. Our lab leverages a combination of cell-specific deletion of UPR genes in mouse models with fluorescence and electron microscopy based bone imaging techniques to understand the molecular mechanisms by which ER regulates osteoblast differentiation.
The health of the ER is monitored by a triad of ER sensor transmembrane proteins ATF6, Ire1a, and Perk. Accumulation of misfolded proteins in the ER results in ER stress and activates the sensor proteins and initiates the Unfolded Protein Response (UPR) to restore homeostasis. If protein folding is unresolved, elevated UPR induces stimulates cytokine production and cell death. Another aspect of ER homeostasis is the ER associated degradation (ERAD) - a retrograde pathway that recognizes and clears misfolded proteins from the ER.
Iyer S, Melendez-Suchi C, Han L, Baldini G, Almeida M and Jilka RL. Elevation of the unfolded protein response increase RANKL expression. Faseb Bioadvances. In press.
Kim HN, Chang J, Iyer S, Han L, Campisi J, Manolagas SC, Zhou D, Almeida M. Elimination of senescent osteoclast progenitors has no effect on the age-associated loss of bone mass in mice. Aging Cell. 2019; 18(3):e12923. PMID: 30773784.
Kim HN, Iyer S, Ring R, Almeida M. The Role of FoxOs in Bone Health and Disease. Curr Top Dev Biol. 2018; 127:149. PMID: 29433736.