Just as the host tumor microenvironment has gained attention in the area of cancer development and spread, the field of infectious disease research has recognized that host-pathogen interactions play a significant role in the progression and therapeutic response during infection. We are now applying some of the lesions we have learned from the study of bone metastasis to the context of bacterial osteomyelitis, to elucidate the active role of bone cells in infection. We have found that S. aureus, the most common pathogen in bone infections, can replicate within cells committed to the osteoclast fate, including mature multinucleated cells. We have also developed new models of S. aureus osteomyelitis initiated by hematogenous (bloodstream) spread, using isolates from pediatric patients. We are now using these models to study the role of osteoclasts and other myeloid lineage cells in the initiation and progression of osteomyelitis.
Veis (Novack) Lab
Molecular and Metabolic Regulation of Bone Mass in Health and Disease
Bone is a dynamic and complex organ whose integrity is controlled by the interaction of many cell types, including osteoclasts which remove bone and osteoblasts which build it. The Veis lab uses transgenic mouse models as well as pharmacological approaches, to understand the molecular and metabolic regulation of bone mass in health and disease states. Another area of interest is how bone cells interact with foreign invaders – in the form of tumor cells or microbes – focusing on the host as a potential therapeutic target. We use a combination of disease models, genetic mouse models, and in vitro cultures, providing a broad range of potential research projects. The research opportunities, combined with personalized mentorship, provide a positive environment in which to develop as a scientist.
Osteomyelitis: an active role for bone cells
Bone cell mitochondria: what do they do?
Mitochondria are critical components of cells, and they are the hub of energy (ATP) production. Recent reports indicate that mitochondria also play a role in cell survival/death, calcium homeostasis, and reactive oxygen species (ROS) production/oxidative stress. A unique feature of mitochondria as organelles is their organization into a highly dynamic network within the cell characterized by the interrelated processes of fusion, fission and removal via mitophagy. Although still not completely understood, this dynamic regulation of the mitochondrial network seems to be important for the maintenance of healthy, properly functioning mitochondria. To support their roles in building and remodeling bone, osteoblasts and osteoclasts have high energy demands, and their activities are dependent on metabolic status. Therefore, we are currently working to understand the role of mitochondrial dynamics in both osteoclasts and osteoblasts utilizing conditional deletion of Mfn2, a critical protein for mitochondrial fusion and mitophagy. Since these bone cells each have a distinct and highly specialized cell biology to support their function, we expect to gain insight into specific mitochondrial functions in the context of bone mass regulation.
- Linda Cox, Research Assistant
- Phil Roper, Postdoc Research Scholar
- Christine Shao, Undergraduate Student