Message from the Chair
Welcome to the Department of Biochemistry in the West Virginia University School of Medicine. This is a very exciting time in the Department as we are in the midst of a period of growth. Within the last few years, three new junior faculty members have joined the Department, expanding our expertise in gene expression and protein biochemistry. Our third and most recent addition is Roberta Leonardi with expertise in metabolism from Suzanne Jackowski's laboratory at St. Jude Children’s Research Hospital. Our next challenge is to replace faculty members who have recently retired/relocated. Over the next few years, we plan to expand our expertise for research in metabolism, obesity and disease. Our growth in these areas aligns with strategic initiatives in the School of Medicine and Health Sciences Center. Important institutional developments in support of these initiatives include establishment of the West Virginia Clinical and Translational Sciences Institute (WVCTSI) and successful competition for an NIH IDeA-CTR award to provide infrastructure for clinical and translation research. Research in obesity and metabolic disease is an area of emphasis for the WVCTSI. Our faculty members also participate in the Obesity, Metabolism and Diabetes program that is part of the Prevention Research Center at WVU. This program seeks to foster collaboration in the study of metabolic diseases across disciplines including the basic and clinical sciences, public health, and community engagement. The Obesity, Metabolism and Diabetes program has organized 2 conferences, the most recent being the Obesity Summit 2014 this past spring. This summit was followed by an RFA from the WVCTSI to fund pilot projects in the area of metabolism. Recent institutional investments also include shared facilities to support metabolic research, at the cellular level (Seahorse extracellular flux analyzer) and with animal studies (Columbus Instruments Comprehensive Lab Animal Monitoring System). Building upon these investments and planned growth in the Department and at the Institution, our goal is the development of a very strong group of laboratories focused upon metabolism and disease.
NIH Grant Awarded
WVU Biochemistry Department researcher wins $1.4 million grant
5 year federal grant will fund investigations into molecular machines that degrade proteins:
MORGANTOWN, W.Va. – The National Institutes of Health has awarded a West Virginia University researcher $1.4 million over five years to investigate how protein degradation machines work at a molecular level. David M. Smith Ph.D. a faculty member in the WVU Department of Biochemistry studies a protein degradation machine called the proteasome. The proteasome is a complex of more than 60 proteins whose major job is to degrade proteins in a high regulated and selective manner. Proteins need to be degraded for a number of reasons: they can get damaged, they get misfolded or don’t fold properly, they are no longer needed by the cell, etc. Smith explained that protein degradation often goes awry in disease. The proteasome and some of its regulators are up-regulated in many types of cancer, and interestingly, in contrast the proteasome fails to properly function in most types of neurodegenerative disease (Alzheimer’s, Huntington’s, ALS, etc..). So we are interested in understanding how the proteasome works and is regulated at the most basic level, so we can better understand it’s biological role in disease.
"The proteasome is a fantastically interesting molecular machine" Smith said. "It’s shaped a lot like a barrel, and the proteolytic sites (scissors that chop up proteins) are located on the inside of the barrel, this ensures that only proteins that are stuffed into the barrel are degraded." The decision about what proteins get degraded are primarily made by various regulatory complexes that bind to the top of the barrel. "These regulatory complexes have several important jobs", David said, "They must recognize the proper proteins and then inject them into the core for their destruction". This multistep process ensures that only the proper proteins are degraded.
Our major goal is to understand how the proteasome uses chemical energy in the form of ATP to regulate this process. One type of regulatory particle, the 19S, has a ring of 6 ATPase subunits. This ring constitutes a motor that grabs proteins, unfolds them, and injects them into the proteolytic core. We want to understand this process: "how chemical energy from ATP is coupled to physical pulling and tugging on proteins", Smith said. A further understanding of these fundamental regulatory mechanisms is essential to develop future drugs that can treat these diseases where protein degradation is misregulated.