- Intrinsically disordered proteins, Alpha-synuclein, Parkinson’s Disease.
Note: I am not currently accepting graduate students.
Ph.D, Cambridge University, Corpus Christi, 1977, Pharmacology
B.A., Cambridge University, Corpus Christi, 1974, Chemistry
D.Sc., University of Saskatchewan, 2007
The long term goal of my research program is to understand protein folding and misfolding and what factors influence these conformational changes. Nanopore analysis is an electrophoretic technique which can interrogate a single protein molecule as it interacts with a pore embedded in a membrane. The electronic signal is exquisitely sensitive to the conformation of the molecule and thus can provide structural information which would be difficult to obtain by conventional methods.
Our work with misfolding proteins is leading to a better understanding of the biochemistry and pathology of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Overall, this program will help to understand why proteins misfold and what might be done to prevent this. In the long term, this knowledge may lead to the development of drugs which could be used to treat neurodegenerative and other protein misfolding diseases.
Jeremy Lee completed a PhD in pharmacology at Cambridge University and his thesis – “The Binding of Antibiotics to DNA" –marked the start of a life-long interest in the structure and function of nucleic acids. Lee’s initial research was analysis of monoclonal antibodies that bind to proteins, DNA or RNA, but it was the discovery of an unusual DNA structure in 1992, called M-DNA, that has dominated his research since. M-DNA has a metal ion in the middle of the DNA helix that causes the DNA to become a conductor of electrons rather than an insulator. It may be the smallest wire imaginable. Potential applications include M-DNA-based diagnostic tools that would quickly yield information on genetic disease and bacterial infection.
Lee is proud of the fact that he has never taken a biochemistry course in his life, but has taught the subject for 25 years to undergraduates and medical and graduate students. His love of teaching is matched only by his hatred of PowerPoint, and he can frequently be seen walking around campus covered in chalk dust.
- Jakova E, Lee J. Behaviour of alpha-synuclein-drug complexes during nanopore analysis with a superimposed AC field. Electrophoresis. 2017;38:350- 360.
- Kakish J, Allen K, Harkness T, Krol E, Lee J. Novel dimer compounds that bind alpha-synuclein can rescue cell growth in a yeast model of Parkinson’s Disease. ACS Chemical NeuroSciences. 2016;7:1671-1680.
- Kakish J, Lee D, Lee JS. Drugs that bind to alpha- Synuclein: Neuroprotectiveor Neurotoxic? ACS Chem. Neurosci. 2015(6):1930-1940.
- Jakova E, Lee JS. Superposition of an AC field improves discrimination between peptides in nanopore analysis. Analyst. 2015;140:4813-4189.
- Kakish J, Tavassoly O, Lee JS. Rasagiline, a suicide inhibitor of MAO-B, binds to alpha-synuclein. ACS Chem. Neurosci. 2015;6:347-355.
- Guo M, Hundseth K, Ding H, Vidhyasagar V, Inoue A, Nguyen C-H, Zaln R, Lee JS, Wu Y. A distinct triplex DNA unwinding activity of CHLR1 helicase. J. Biol. Chem. 2015;290:5174-5189.