Research focus
The bone microenvironment in cancer and infection
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. A major 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 as well as diverse technical approaches. Most of our projects are collaborative, taking advantage of the wealth of expertise in the WashU Musculoskeletal Research Center. The research opportunities, combined with personalized mentorship, provide a positive environment in which to develop as a scientist.
Current projects
For many years, our lab has had an interest in breast cancer bone metastasis, particularly the role of the osteoclast. Although Dr. Veis maintains several collaborations in this area, recently, we have turned experimental attention towards a rare tumor that causes osteolysis, Acute T Cell Leukemia (ATL). This malignancy is caused by infection of T cells with HTLV-1, a retrovirus endemic in Asia and the Caribbean. We are using several different models of ATL – established tumor cell lines, patient-derived xenografts, HTLV-1 infected human T cells (ie. newly immortalized lines), and HTLV-1 infection of mice with humanized immune systems. These enable a variety of in vivo and in vitro systems to discover factors that mediate tumor-bone interactions including small extracellular vesicles (EVs). In addition to exploring how HTLV-1 infection impacts the bone, we also consider how the activity of bone cells in turn affects the behavior of malignant and pre-malignant HTLV-1+ T cells.
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. Rather than sequestering nutrients away from the invading bacteria, osteoclasts seem to feed them. Infections including osteomyelitis are more common in diabetics. We are interested in how this metabolic condition affects the interactions of S. aureus with bone cells to allow soft tissue infections to progress to osteomyelitis.
Questions that we hope to address in the lab include: 1) What is the role of osteoclasts in the initiation and progression of osteomyelitis? 2) How do bacteria obtain nutrients from osteoclasts to grow? 3) How does hyperglycemia affect bone cells, especially at the periosteum, to allow progression of osteomyelitis in diabetes?
Publications
Lab members
- Linda Cox, Research Assistant
- Luke O’Connor, PhD Candidate
- Nitin Pokhrel, PhD, Instructor
- Yuyang Zhou, MS, Research Assistant
Join this lab
To inquire about available positions for DBBS graduate students or postdocs, please contact Dr. Veis by email at dveis@wustl.edu.
