Title: The role of autophagy in the osteoblast lineage cells
There are three types of autophagy (macroautophagy, chaperone-mediated autophagy (CMA), and microautophagy), which differ in their target specificity, the mechanism by which they deliver their targets to lysosomes, and the timing of their response to stressors. In addition to stress response, autophagy pathways have additional functions in specific cell types. The contribution of different autophagy types to osteoblast lineage cell function is not clear. We propose the central hypothesis that macroautophagy and CMA promote the survival and function of osteoblast lineage cells. To address this hypothesis, we will pursue the following specific aims:
- Identify mechanisms by which the loss of macroautophagy in osteoblast lineage cells reduces bone formation.
- Determine whether CMA protects osteoblasts and osteocytes from ER stress in vivo and
- Determine whether stimulation of macroautophagy improves osteoblast function in stress-associated conditions.
Melda Onal is a Molecular Biology and Genetics major. She obtained her Ph.D. in UAMS in the Center for Osteoporosis and Metabolic Bone Diseases. Her graduate training combined molecular and cell biology techniques to understand bone physiology. She completed my postdoctoral training at the University of Wisconsin – Madison. During her postdoctoral research, she was trained in unbiased genomewide techniques that analyze transcriptional regulation. With the help of these techniques and novel technologies like CRISPR/Cas9, she was able to utilize transcriptional regulation of certain genes to expand our understanding of calcium-phosphate metabolism. In late 2017, she joined UAMS as an assistant professor. In her lab, they are trying to address the role of different types of autophagy, their crosstalk with each other, and their roles in bone physiology and pathophysiology. For this purpose, they combine a number of cell and molecular biology techniques and produce novel murine models.
Dr. Onal’s Mentors
Steve Barger, Ph.D., is a Professor of Geriatrics, Neurobiology and Developmental Sciences, and Internal Medicine. Dr. Barger’s primary interest is in the events related to neuronal death caused by pathological insults (especially, excitotoxicity) and the protection against these insults afforded by changes in gene expression. Particular focus has been given to interactions between proteins implicated in the pathogenesis of Alzheimer’s disease. His laboratory also characterizes effects of these proteins and neurotransmitters on gene expression.
Elena Ambrogini, M.D., Ph.D., is an Associate Professor in the Division of Endocrinology and Metabolism, Internal Medicine, UAMS. The main research interests of Dr. Ambrogini are in the field of endocrinology and particularly in bone and calcium homeostasis, and thyroid diseases. Her work is particularly focused on the pathophysiology of osteoporosis and metabolic bone diseases. These studies have been the object of oral presentations at International Meetings and publications.