The ability of cells to proliferate appropriately and adapt to changing environments is fundamental to development, tissue homeostasis, and human health. Failures in these processes contribute to cancer and numerous other diseases. Our laboratory investigates the molecular mechanisms that control cell proliferation, with a particular focus on how signaling networks regulate protein function, gene expression, and cellular behavior. We seek to understand both how cells execute normal proliferation programs and how they adapt to sustain growth during chronic stress. By combining genetics, functional genomics, and quantitative approaches in yeast and human cells, we uncover fundamental principles of cellular regulation that are broadly relevant to health and disease.
Decoding Phosphorylation-Dependent Regulation of Cell Cycle Proteins
Protein phosphorylation is one of the most important mechanisms used to regulate cell proliferation, yet for most phosphoproteins we do not know which sites are functionally important or how multiple phosphorylation events work together to control activity. Our lab develops and applies high-throughput approaches to systematically decode phosphorylation-dependent regulation of cell cycle proteins. Using methods such as Phosphosite Scanning, we seek to uncover the "phosphorylation logic" that governs protein function and cellular behavior. Current projects investigate how multisite phosphorylation controls transcription factors and other cell cycle regulators in both yeast and human cells.
Proliferation and Adaptation During Chronic Stress
Cells must constantly balance growth with survival as environmental conditions change. Although stress often triggers cell-cycle arrest, successful adaptation ultimately requires cells to reestablish proliferation while remaining under adverse conditions. Our lab studies how stress-response pathways reshape signaling networks, protein function, and gene expression programs to enable this transition. By uncovering the molecular mechanisms that allow cells to proliferate during chronic stress, we aim to reveal fundamental principles of cellular adaptation that are relevant to diverse biological processes and diseases, including cancer progression and metastatic growth, as well as the survival and persistence of fungal pathogens within the host.
Protein Degradation and Cell Cycle Control
The ubiquitin-proteasome system plays a critical role in regulating cell proliferation by controlling the abundance and activity of key cell-cycle proteins. Our lab has a longstanding interest in understanding how ubiquitin ligases and deubiquitinating enzymes recognize their substrates and how regulated protein degradation contributes to robust cell cycle control. We continue to explore fundamental questions surrounding protein turnover and its integration with phosphorylation- and transcription-based regulatory networks.