Milad Alasady, Ph.D.

The heat shock response (HSR) is an adaptive mechanism present in all cellular life, essential for maintaining proteome health during elevated temperatures and other proteotoxic stresses. The HSR encompasses cellular machinery involved in protein quality control, folding, trafficking, and degradation. In response to proteotoxic insults, the HSR is rapidly activated by triggering heat shock factor 1 (HSF1), which drives the transcription of heat shock proteins (HSPs). These HSPs, such as Heat Shock Protein 70 (HSP70), act as molecular chaperones, helping proteins maintain their proper folded and functional states. This mechanism helps protect cells from the accumulation of misfolded and aggregated proteins, which can otherwise lead to cellular cytotoxicity, resulting in neurodegeneration and aging. Although the HSR evolved to safeguard cells, it is often co-opted by cancer cells to enhance their survival during malignant transformation and acquire drug resistance during cancer treatment. Our long-term goals are to identify and characterize the molecular mechanisms underlying HSF1-mediated regulation of transcription in cancers, understanding the molecular mechanisms by which HSF1 and HSP70 drive chemotherapeutic resistance in cancer, and exploring potential strategies to manipulate these networks to improve pharmaceutical treatment outcomes for human cancer.