Price, John

Background

BS Chemistry, Utah State University (2001)PhD Biochemistry and Molecular Biology, Pennslyvania State University (2005)Postdoctoral Fellow studying Prion Biology with Stanley Prusiner, University of California, San Francisco (2005-2010)

Cancer Research

My research explores mechanisms used by living cells to control the synthesis and degradation of protein. Specifically, we use mass spectrometry and stable isotopes to label newly synthesized molecules with a time dependent tag. This allows us to measure both in vivo concentrations, and replacement rate. With a mass spectrometer, the time-dependent stable isotope enrichment can be measured in any molecule of a complex mixture, allowing us to monitor large numbers of proteins simultaneously and perform experiments that survey broad sections of the proteome. We have successfully used this technique in many different biosynthetic systems from "cell free" environments to humans (see Figure and Figure Legend).

Currently, we are focused on understanding post-transcriptional control of the proteome composition within cells, focusing on the use of stored mRNA and protein degradation

Post-transcriptional control of cell metabolism using stored mRNA. Multiple processes critical to human health are known to employ stored mRNA, yet these systems are difficult to investigate using current tools. The mRNA is present in the cell for an indefinite period of time before signal dependent translation of the specific protein occurs. By following signal specific protein synthesis we can approach the understanding of these systems from the "bottom up" to identify the biochemical pathways activated within the cell.

Maintenance of proteome homeostasis through protein catabolism. Many of today’s most devastating diseases can be identified as diseases of protein homeostasis. Parkinson’s, Alzheimer’s, Huntington’s, diabetes and other diseases all exhibit cellular deposits of aggregated protein. These aggregates are often highly resistant to degradation and may indicate a dysfunction within the catabolic machinery of the cell. Continuous protein catabolism is critical in the presence of constitutive transcription and translation, yet these processes are poorly understood. It has recently been shown that the cell employs thousands of proteins, (ubiquitin ligases, targeted proteases, proteasome, etc.) to guide the process of protein degradation. Thus, the complexity of the regulatory structure for removing a protein from the cell may be comparable to producing the protein in the first place. Our current work is focused on identifying the substrates for cellular proteases and understanding how targeted proteolytic processing is used by the cell.