My research aims to understand the mechanisms by which cells survive under adverse conditions that cause protein damage. The hallmark of proteotoxic stress is the accumulation of unfolded proteins and, as a consequence, the loss of cellular protein homeostasis and function. Eukaryotic cells respond to the presence of misfolded proteins by activating the expression of molecular chaperones or heat shock proteins (HSPs). Cells undergo coordinated changes in their gene expression program to prioritize the production of sufficient HSPs that will prevent misfolded proteins to form toxic aggregates. Once HSPs have refolded the damaged proteins or cleared them by degradation, the stress response is specifically attenuated.
My area of study focuses on decoding the molecular pathways driving the regulation of HSP expression. To resolve this biological process in time and space, I monitor individual HSP mRNAs biogenesis using single molecule fluorescence microscopy technologies in fixed and live cells. These approaches will help to better understanding the etiology of diverse diseases caused by the loss of cellular homeostasis. Important examples are the stunted stress response of hippocampal neurons that leads to age-related neurodegeneration and the uncontrolled production of HSPs by tumor cells that precludes therapy efficacy.
My long-term goal is to determine how the stress response can be therapeutically manipulated to treat cancer and neurodegenerative diseases.