Penn Medicine Biochemist Receives Major Award for Research on Epigenetic Protein Modifications via Mass Spectrometry
Techniques Hold Significant Implications for Understanding Disease Mechanisms and Detection
Newswise — PHILADELPHIA - Benjamin A.Garcia, PhD,an expert in quantitative proteomics andPresidential Professor of Biochemistry and Biophysics in the Perelman School of Medicine at the University of Pennsylvania,has been awarded the Biemann Medal by theAmerican Society for Mass Spectrometry (ASMS). The early-career award recognizes significant achievement in basic or applied mass spectrometry.
Garcia’s lab has developed and refined mass spectrometry analysis techniques for analyzing proteins that are considered state of the art and used world-wide by researchers. Proteins, modifications to them, and their various forms are the driving forces of cellular machinery that control crucial physiological events.
Mass spectrometry is a technique for detecting the components of a sample—solid, liquid, or gas—by their mass and charge. It can determine which molecules make up a sample based on the spectrum created by the ions that are present. The process can detect proteins and biomarkers (chemical signposts for certain diseases), and enable the study of their structure, especially in low concentrations. Applications in caring for patients include analyzing proteins for diagnostic testing, monitoring the effectiveness of drug therapy, and identifying causes of disease for targeted therapies.
Garcia was recognized for contributions to better understanding of the histone code, the set of modifications in histone proteins that are crucial for regulating gene expression. In humans and other animals, histones function as spools for the thread-like DNA to wrap itself around. They play a key role in normal cell division, which is essential for life, but they also are involved in cellular development and drive certain cancers. Most proteins undergo modification once they are translated, and these modifications dictate their cellular functions.
Garcia’s lab has developed a number of experimental and computational methods to detect histone post-translational modifications, quantify their relative abundance, monitor their inter-cellular activities, and pinpoint the modifications on specific genome locations. In particular, Garcia has pioneered high-throughput, “bottom-up” methods for detecting post-translational histone modifications and quantitative comparison of multiple cellular states. (High-throughput refers to sequencing massive amounts of DNA from many different people at once.) His expertise also includes “middle down” approaches that enable detailed analysis of histone proteoforms, which are histones with concurrently occurring modifications.
In both the bottom-up and middle-down approaches, a key goal is to utilize large volumes of protein-centered data to improve understanding of biological processes such as post-translational modifications at the molecular level, helping elucidate the mechanisms of various diseases and eventually identifying treatments for them. For example, it is currently unknown what effects, if any, multiple combinations of histone modifications might exert. Sophisticated mass spectrometry analysis developed by Garcia is enhancing investigations of such histone modifications to a much higher scale. In combination with cell and biochemical experimentation, bioinformatics analysis, and other technologies, it can create a systems biology outlook that lays the foundation for development of drug treatments for many human diseases.
In recognizing Garcia the Society said: “These methods have made unique impact in chromatin [chromosome] biology and epigenetics research [the study of biological mechanisms that switch genes on and off], and have been fully embraced by a growing number of research groups from all over the world.”
The Biemann Medal was established to honor the late Professor Klaus Biemann of the Massachusetts Institute of Technology. It will be formally conferred at the ASMS Annual Conference in San Diego in June; Garcia will deliver a lecture at the event.
Garcia received his bachelors in chemistry from the University of California at Davis and his doctorate in chemistry from the University of Virginia at Charlottesville.
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