Rodrigo Franco, PhD
Cell Death and Redox Signaling
Cell death is a central phenomenon in the etiology of several human diseases including cancer and neurodegenerative disorders. It has been demonstrated that alterations in the cellular redox balance regulate the activation of distinct signaling cascades leading to the progression of a variety of cell death programs. However, the exact mechanisms involved in the regulation of cell death by redox signaling are still far from being understood.
In our research group we aim to elucidate the molecular mechanisms involved in the regulation of cell death progression by redox signaling. Because the intracellular thiol-disulfide (GSH/GSSG) balance is considered the major determinant of the redox status of the cell, we are particularly interested in studying how alterations in thiol homeostasis regulate the activation/inactivation of the cell death machinery during the pathogenesis of cancer and neurodegeneration.
Environmental Toxicity and Oxidative Stress
The environment represents a key contributor to human health and disease. Exposure to many toxicants such as metals and pesticides have detrimental effects on health and are considered to contribute substantially to a number of diseases of major public health significance. It has been recognized that many of the toxic effects induced by environmental stressors are mediated by regulation/induction of cell death and oxidative stress whose deregulation has been associated to several environmental diseases. The overall impact of environmental changes on the mechanisms of cell death progression is poorly understood yet the consequences of modifying/regulating them can result in a potential increased risk of developing diseases such as cancer and neurodegeneration, which are associated to alterations in cell death rates. We are interested in identifying the molecular mechanisms by which oxidative stress regulates cell death during environmental toxicity.
Cytotoxic Brain Edema
Cytotoxic swelling is an important component of brain edema which occurs during distinct pathological states including hyponatraemia, traumatic brain injury, ischemia and hepatic encephalopathy. It is the result of a deregulated cell swelling of neurons and glia and the subsequent reduction in the extracellular space. Cytotoxic edema results mainly from both extracellular and/or intracellular osmotic disturbances and is also associated to the impairment of volume regulatory mechanisms. In our research group, we are also studying the signaling cascades involved in the regulation of cytotoxic swelling. We are particularly interested in characterizing the signaling events that modulate the activation of ionic/osmolyte efflux pathways under these circumstances.