Department of Biochemistry

Name: Sanders, Charles R.
Title: Professor of Biochemistry and Medicine, Investigator: Center for Structural Biology and Institute for Chemical Biology, Professor of Medicine, Aileen M. Lange & Annie Mary Lyle Chair in Cardiovascular Research
Department: Biochemistry
Office Address: Rm 5110C BIOSCI/MRBIII
Phone Number: (615) 936-3756
E-mail: chuck.sanders@vanderbilt.edu
Lab URL: https://structbio.vanderbilt.edu/sanders

Research Keywords: membrane proteins, disease, Charcot-Marie-Tooth, myelin, folding, misfolding, structural biology, NMR, spectroscopy, membrane, protein structure, lipid rafts, neuropathy, neurodegeneration, enzymes, neuroscience, single nucleotide polymorphisms, SNPs, Alzheimer’s, potassium channels, KCNQ1, PMP22, integrins, amyloid, channels, biophysics, biochemistry, chemical biology, drug discovery, high throughput screening

Research Specialty: Structural and chemical biology of membrane proteins. Membrane protein misfolding and disease. Alzheimer’s disease, Charcot-Marie-Tooth Disease, cardiac arrhythmias, kidney fibrosis. Drug discovery

Research Description: Molecular Biophysical Basis and Drug Discovery for Diseases Related to Membrane Protein Dysfunction and Misfolding  A surprising number of diseases are caused or impacted by missense mutations in genes encoding membrane proteins that result in protein dysfunction and/or misfolding and mistrafficking early in the secretory pathway. We seek to elucidate the molecular biophysical mechanisms by which such mutations result in these defects.  We are also carrying out drug discovery efforts to leverage our knowledge of disease mechanisms as the basis for development of therapeutics.

Current projects focus on peripheral myelin 22 (PMP22) and its role in Charcot-Marie-Tooth Disease (CMT), a peripheral neuropathy, and on the KCNQ1 potassium channel and its role in long-QT syndrome (LQTS).  CMT and LQTS are both top-10 genetic disorders in terms of prevalence in the human population.  For both of these disorders we have shown that a majority of the disease-causing mutations act by destabilizing PMP22 and KCNQ1, result in their misfolding, mis-trafficking, loss of function, and—in some cases—formation of toxic aggregates.   In recent drug discovery work we have found molecules that favorably restore normal trafficking of both proteins, potentially paving the way to therapeutics based on these compounds.

Studies employ a wide range of techniques spanning the range from chemical biology and high throughput screening to molecular biophysics/spectroscopy/biochemistry to cellular/molecular biology. Additional information is found at the lab web site: http://structbio.vanderbilt.edu/sanders

Training in the Sanders Lab: Trainees in the Sanders lab are also broadly trained in membrane protein biochemistry and biophysics, usually also with good doses of chemical biology and cell biology.  Most projects involve collaborations with other labs here or outside of Vanderbilt.  Students and postdocs are also constantly exhorted to master the literature related to their project and to develop a strong biomedical perspective for their work.

Finally, Dr. Sanders believes that is very important for trainees to be taught the ins and outs of the research culture, including funding strategies, peer review service, and how to be a good collaborator and colleague.  Required reading for prospective trainees is  “What is Expected of a Ph.D. Student or Postdoctoral Fellow in the Sanders Lab?” which can be accessed on-line at:

http://structbio.vanderbilt.edu/sanders/Sanders_Lab_Guide_Comprehensive.pdf

PubMed Listing of Dr. Sanders’s Publications