What Fascinates Us

An overarching theme of the Klevit lab is to understand guardians of the cell. We focus on two broad topics: guardians of the genome and guardians of the proteome. In the former category, the modification of nucleosomal histones with ubiquitin is emerging as a mark that is involved in the DNA damage response, transcriptional regulation, and maintenance of epigenetic marks. Our current focus in this realm is the breast cancer susceptibility protein, BRCA1, and its “sister gene,” BARD1. In the second category, the small heat shock proteins (sHSPs) play key roles both in cellular housekeeping and as a cell’s first responders in times of stress. These enigmatic protein chaperones are involved in a growing number of human diseases and syndromes, especially neurodegenerative disease, cardiomyopathies, and cataract, but their mechanism of action remains virtually entirely undefined.