Title: Role of the unfolded protein response in skeletal homeostasis.
The central hypothesis of this project is that components of the UPR play an essential role in osteoblast differentiation and function, and that dysregulation of the UPR in cells of the osteoblast lineage contributes to pathological bone loss.
Three specific aims are proposed to address this hypothesis:
- Determine whether Perk plays an essential role in osteoblast physiology,
- Determine the skeletal consequences of sustained elevation of the UPR in osteoblast-lineage cells, and
- Determine if glucocorticoid excess inhibits bone formation in mice by suppressing UPR activation.
Dr. Iyer joined the UAMS Department of Orthopaedic Surgery as an Assistant Professor in 2016. She joined the laboratory of Maria Almeida as a postdoctoral fellow in 2010 and began a project to understand how oxidative stress inhibits bone formation. As part of these studies, she discovered that stress-activated transcription factors suppress bone formation by inhibiting the Wnt signaling pathway in osteoblast progenitors. In recognition of her achievements, she received a Young Investigator Award from the American Society for Bone and Mineral Research in 2011.
Dr. Iyer’s Mentors
Giulia Baldini, M.D., Ph.D., Professor, Department of Biochemistry, UAMS. Research interests include studying obesity as a major risk factor in the development of the metabolic syndrome and lipid stress, such as that induced by high fat diet, affects MC4R abundance, signaling, and intracellular traffic; whether chemical chaperones can rescue function of MC4R in lipid stressed neurons; and whether different synthetic MC4R agonists have specific effects to promote MC4R signaling.
Roy Morello, Ph.D., Associate Professor, Division of Genetics, Department of Orthopaedic Surgery. Research interests include the study of function of novel genes, in particular those involved in connective tissue formation, development, homeostasis and disease, with an emphasis on the skeleton and the study of osteocytes in osteogenesis imperfecta and their potential role in driving high bone turnover, and study of the role of collagens and collagen-modifying proteins in other tissues, including the lung and the reproductive system.