My scientific interests span the range of organs to molecules, and the development of new technical methods. For the last twenty years, I have focused on cell mechanics and the mechanisms by which mechanical forces are transduced into cellular signals. We discovered mechanosensitive ion channels in 1983, and since then have studied the channel and cell biophysics. Our methodology includes patch clamp, high resolution light microscopy, real time fluorescence microscopy, high speed digital microscopy, TIRF, digital image analysis, high voltage EM, EM tomography, AFM, molecular biology, natural product and recombinant protein biochemistry and structural NMR. We have discovered a specific inhibitor of mechanosensitive ion channels - a small peptide found in tarantula venom. Not only does it block the channels, but it may have clinical applications for brain tumors, muscular dystrophy and cardiac arrhythmias.

In addition to the work on mechanosensitive ion channels, we have studied voltage and ligand gated channels including P2X2 and Shaker channels. We are studying votlage-dependent channel dynamics using combined AFM and patch clamp. This AFM technique is also being applied to prestin, the motor protein from outer hair cells of the cochlea.

My lab has spent much time in the development of software for the analysis of Markovdata data.The random data that is typical of single channels. This friendly software allow lay users to do simulation and to apply Hidden Markov analysis to convert time domain data to state models. The software has been used not only for ion channel kinetics but molecular motors and the sleep cycle for rats. For the last eight years we have taught hands-on courses to use the software. The course has attracted scientists from academia, industry and government

In addition to software, we develop hardware. For example, our pressure servo is manufactured and sold by ALA scientific. We do microfabrication projects in silicon technology for microfluidics and AFM cantilevers. Many of these projects have been funded by SBIR grants. A number of patents patents have been issued to laboratory members.

Techniques in use:

1. Patch clamp
2. AFM (+patch clamp)
3. Low light digital imaging (Ca+2/Na)
4. Confocal microscopy
5. High speed digital imaging
6. Molecular biology
7. Natural products chemistry
8. Computer Modeling of the Heart and other tissues
9. Mathematical modeling of channels

Funding:

NIH, Japan Science and Technology, Keck Foundation, Novascan Technology, IBM, Hubbard Foundation, Zeneca Pharmaceuticals, NPS Pharmaceuticals, NSF, NASA, USARO, AHA, MDA, Orion, Burleigh Instruments, Sutter Instruments