Michal Toborek, M.D., Ph.D.
Professor of Biochemistry and Molecular Biology
Description of Research
The main research interest in Dr. Toborek’s laboratory is focused on the involvement of the blood-brain barrier (BBB) in the pathomechanisms of cerebrovascular disorders and neurodegenerative disorders, including the development of brain metastases. Dr. Toborek’s laboratory is recognized for studies on the effects of environmental, infectious, and behavioral factors on the integrity and functions of the BBB. Specific interests are focused on studies on how the adhesive and chemotactic properties of the brain endothelium can influence transendothelial migration of tumor cells into the brain. Important aspects of this project involve evaluation of the protective effects of exercise against the development of brain metastases.
Moderate to vigorous exercise is a powerful means to reduce metastatic cancer incidence. Our research is specially focused on the mechanisms of tumor cell extravasation into the brain. Such an emphasis is consistent with our interest in the BBB pathology. In addition, brain metastases are one of the leading causes of cancer-related morbidity and mortality. They occur in 30-40% of all systemic malignancies and contribute to an estimated 200,000 new cases annually, a number that is expected to increase dramatically in the coming years.
The central hypothesis of our research is that exercise protects against the development of blood-borne brain metastases by increasing antioxidant capacity and modulating redox-regulated responses in the capillary endothelium. Mechanistically, we explore a link between disruption of the BBB and alterations of caveolae-associated redox signaling in brain capillaries during tumor cell extravasation. Caveolae are the subset of lipid rafts that are characterized by the presence of caveolin proteins. Their significance is related to the fact that a variety of cell surface receptors and redox-regulated signaling pathways, including small GTPases such as the Ras and Rho cascades, are localized in caveolae. These pathways may participate in phosphorylation of tight junction proteins and influence the opening and closing of tight junctions. Another area of interest in cancer research is related to the influence of environmental pollutants, called polychlorinated biphenyls (PCBs).
- Found that exercise is a modifiable behavioral factor that can influence the development of experimental brain metastasis
- Established models of brain metastasis in mice
- Performed detailed studies on the mechanisms of PCB-mediated facilitation of brain metastasis development
Selected Cancer-Related Publications
- Wolff G, Toborek M. Targeting the therapeutic effects of exercise on redox-sensitive mechanisms in the vascular endothelium during tumor progression. IUBMB Life 65:565-71,2013 Read more »
- Wrobel JK, Seelbach MJ, Chen L, Power RF, Toborek M. Supplementation with selenium-enriched yeast attenuates brain metastatic growth. Nutr Cancer 65:563-70,2013 Read more »
- Zhang B, Choi JJ, Eum SY, Daunert S, Toborek M. TLR4 Signaling Is Involved in Brain Vascular Toxicity of PCB153 Bound to Nanoparticles. PLoS One 8:e63159,2013 Read more »
- Sipos E, Chen L, András IE, Wrobel J, Zhang B, Pu H, Park M, Eum SY, Toborek M. Proinflammatory adhesion molecules facilitate polychlorinated biphenyl-mediated enhancement of brain metastasis formation. Toxicol Sci 126:362-71,2012 Read more »
- Zhang B, Chen L, Choi JJ, Hennig B, Toborek M. Cerebrovascular Toxicity of PCB153 is Enhanced by Binding to Silica Nanoparticles. J Neuroimmune Pharmacol 7:991-1001,2012 Read more »
Collaborating in the Multidisciplinary Research Program(s):