Research Focus

In all cell types, stability and renewal of the proteome is maintained by fine-tuned control of protein homeostasis. Dysfunction/decline in proteostasis is one of the hallmarks of aging. One of the proteostasis mechanisms implicated in aging is autophagy. Based on the delivery mechanisms utilized to transfer the targets to the lysosomes, autophagy is separated into three types: macroautophagy, chaperone-mediated autophagy, and microautophagy. Our laboratory is focused on roles of different types of autophagy for bone remodeling in health and disease.

 

Publications

Autophagy and Bone:

* Onal M, Piemontese M, Xiong J, Wang Y, Han L, Ye S, Komatsu M, Selig M, Weinstein RS, Zhao H, Jilka RL, Almeida M, Manolagas SC, O’Brien CA. Suppression of autophagy in osteocytes mimics skeletal aging. J Biol Chem. 2013 Jun 14;288(24):17432-40. PMID: 23645674

* Piemontese M, Onal M, Xiong J, Wang Y, Almeida M, Thostenson JD, Weinstein RS, Manolagas SC, O’Brien CA. Suppression of autophagy in osteocytes does not modify the adverse effects of glucocorticoids on cortical bone. Bone 2015 Jun;75:18-26. doi: 10.1016/j.bone.2015.02.005. PMID: 25700544

* Piemontese M, Onal M, Xiong J, Han L, Thostenson JD, Almeida M, O’Brien CA. Low bone mass and changes in the osteocyte network in mice lacking autophagy in the osteoblast lineage. Sci Rep. 2016 Apr 11;6:24262. doi: 10.1038/srep24262. PMID: 27064143

Development of in vivo osteocyte-specific loss of function models:

* Xiong J , Piemontese M , Onal M , Campbell J , Goellner JJ , Dusevich V , Bonewald L , Manolagas SC , and O’Brien CA.  Osteocytes, not osteoblasts or lining cells, are the main source of the RANKL required for osteoclast formation in remodeling bone. PLoS One. 2015 Sep 22;10(9):e0138189. doi: 10.1371/journal.pone.0138189. PMID: 26393791

* MacLeod RS, Cawley KM, Gubrij I, Nookaew I, Onal M, O’Brien CA. Effective CRISPR interference of an endogenous gene via a single transgene in mice. Sci Rep. 2019;9(1):17312. Published 2019 Nov 21. doi:10.1038/s41598-019-53611-6 PMID 31754144

 

Projects

* Roles of different types of autophagy in skeletal homeostasis during health and disease

* Development of CRISPR interference (CRISRi) as an alternative to Cre-loxP system

  • Center for Musculoskeletal Disease Research COBRE pilot grant Onal (PI)      2018-2019

Role of Chaperone Mediated Autophagy in Osteoblast Lineage Cells of the Bone

Agency: NIH and Bone Joint Initiative UAMS

  • National Institute of Arthritis and Musculoskeletal and Skin Diseases R21  Onal (PI)    2020-2022

CRISPR interference as an alternate for Cre-loxP

Agency: NIH, NIAMS

 

Lab Personnel

Nisreen Akel