Charles R. Sanders, Ph.D.
Senior Advisor to the Dean of Basic Sciences
Professor of Biochemistry & Medicine
Aileen M. Lange & Annie Mary Lyle Chair, Cardiovascular Research
Structural & chemical biology of disease-related membrane proteins
Research Keywords: membrane proteins, folding, misfolding, PMP22, KCNQ1, PERP, Charcot-Marie-Tooth disease, long-QT syndrome, neuropathy, neurodegeneration, cardiac arrhythmia, personalized medicine, precision medicine
Research Specialty: Determination of how defects in membrane proteins cause disease, and translation of the resulting insight into drug discovery.
Research Description: Gene variations that encode amino acid changes in human membrane proteins often result in decreased folding of the mutated membrane protein, leading to mistrafficking of the protein, loss of function, and disease. We seek to elucidate the molecular biochemical and biophysical mechanisms underlying misfolding and disease. We are also carrying out drug discovery efforts to leverage our knowledge of disease mechanisms to develop new therapeutics.
Current Sanders Lab projects focus on:
- Peripheral myelin protein 22 (PMP22) and its role in Charcot-Marie-Tooth Disease (CMT), a peripheral neuropathy that is a top-10 genetic disease.
- The KCNQ1 potassium channel and its role in long-QT syndrome (LQTS) cardiac arrhythmia. LQTS is also a top-10 genetic disorder.
- PERP (P53 Apoptosis Effector Related To PMP22). Amino acid variations in PERP cause certain skin disorders. This is a new project.
For all three projects we are investigating the molecular mechanisms underlying these disease and using the resulting insight as the basis for efforts to develop drugs that treat these diseases by addressing the fundamental disease mechanisms. Studies employ a wide range of techniques spanning the range from biophysics and biochemistry to cell biology, to chemical biology and high throughput screening. Additional information is found at the Sanders Lab web site: http://structbio.vanderbilt.edu/sanders The lab is part of the Vanderbilt Center for Structural Biology, the Vanderbilt Institute of Chemical Biology, and the Department of Biochemistry.
Significance: There are thousands of human diseases that are caused by heritable gene variations that encode changes in the amino acid sequence of the associated protein. Very often, there is not just a single variant for a given gene/protein that causes a given disease, but rather a whole spectrum of known variations, any one of which can trigger the disorder. For a given disease-linked protein this raises important questions such as: (i) do all disease-causing variations act through the same mechanism or does this change from variant-to-variant? (ii) What are these mechanisms? (iii) Is it possible to use insight from the mechanistic studies as the basis for precision medicine drug discovery? Previous studies from the Sanders Lab have established misfolding and mistrafficking of PMP22 and KCNQ1 as the basis for a majority of cases of Charcot-Marie-Tooth disease and long-QT syndrome, both top-10 genetic disorders. We are leveraging our insight from studies of these systems to discover drugs that address the specific defects associated with particular PMP22 and KCNQ1 variants.
Postdoctoral Position Availability and Details: Postdoctoral positions are available. Please submit a cover letter and CV.