Research Focus
The Dole laboratory primarily focuses on how obesity and loss of body weight impact bone health and contribute to skeletal etiologies like osteoporosis and osteoarthritis. The current studies cover three major themes:
- The interplay of early-life factors, including prenatal and postnatal nutrition on the development and maintenance of the skeleton
- Epigenetic and molecular biomarkers associated with obesity and weight loss in bone
- Role of mitochondrial energetics in skeletal and extraskeletal functions of bone (mineral and whole-body energy metabolism)
We utilize in animal models of obesity and weight loss, as well as in vitro approaches to study bone energetics, cellular and tissue level mitochondrial dynamics, and whole-body metabolism. We use micro-CT, histology, genomics and proteomics, and flexural strength tests to characterize mass, architecture, and quality of bone in conditions of chronic metabolic stress. Our ultimate goal is to leverage bone as a therapeutic target to lessen the burden of chronic metabolic diseases and improve physical function and quality of life.
Current Projects
- Investigating the role of nutriepigenomics in regulating bone health during obesity.
- Determining molecular mechanisms that promote inflammation, senescence, and bone fragility in chronic metabolic diseases.
- Identifying osteokines involved in the disruption of whole-body energy metabolism during obesity.
Publications
- Dole NS, Yoon J, Monteiro DA, Yang J, Mazur CM, Kaya S, Belair CD, Alliston T. Mechanosensitive miR-100 coordinates TGFβ and Wnt signaling in osteocytes during fluid shear stress. FASEB J. 2021 Oct;35(10):e21883. doi: 10.1096/fj.202100930. PubMed PMID: 34569659; PubMed Central PMCID: PMC9153140.
- Dole NS, Yee CS, and Alliston T. Osteocyte-Specific TGFβ Signaling Mitigates Obesity-Induced Deregulated Energy Metabolism and Compromised Bone Quality. Journal of the Endocrine Society, Volume 5, Issue Supplement_1, April-May 2021, Pages A441–A442, https://doi.org/10.1210/jendso/bvab048.902
- Dole NS, Yee CS, Mazur CM, Acevedo C, and Alliston T. TGFβ regulation of perilacunar/canalicular remodeling is sexually dimorphic. J Bone Miner Res. 2020, May 8; 4(Suppl 1). PMCID: PMC7209389 doi:10.1002/jbmr.4023.
- Dole NS, Mazur CM, Acevedo C, Lopez JP, Monteiro DA, Fowler TW, Gludovatz B, Walsh F, Regan JN, Messina S, Evans DS, Lang TF, Zhang B, Ritchie RO, Mohammad KS, Alliston T. Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling. Cell Rep. 2017, 28;21(9):2585-2596. PubMed PMID: 29186693, PMCID: PMC6014615.
Grants
Ongoing Grants
- NIH-NIDDK-K01 Mentored Research Scientist Award – 10/1/2021-8/1/2026
- Arkansas Biosciences Institute – 4/1/2022-4/1/2026
- Musculoskeletal Creativity Hub Pilot Grant – 1/1/2023-1/1/2024
Completed Grants
- UCSF Ortho-NOVA grant
Dole (PI)
07/01/2021-06/01/2022
Title: Studying the role of ghrelin in obesity-induced osteocyte energetics and senescence - UCSF-CCMBM Junior Investigator Research Grant
Dole (PI)
12/01/2020-11/01/2021
Title: Understanding the role of Sirt1 in obesity-induced metabolic dysfunction of osteocytes - OREF/ORS Postdoctoral Fellowship Grant: 17-008
Dole (PI)
07/01/2017-06/30/2018
Title: The role of TGFβ in regulating perilacunar remodeling in diabetes
Lab Members
- Vivek Khanal, Ph.D., Postdoctoral Fellow
- Madeline Carroll, B.S., Research Technician
- Jayden Carter, B.S., Research Technician