Professor

Lewis Hall, 3132
Office: (757) 446-5652
Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Professional Experiences

• Professor, Eastern Virginia Medical School, 1991-present
• Associate Professor, Eastern Virginia Medical School, 1986-1990
• Adjunct Associate Professor, Old Dominion University, 1986-1990
• Assistant Professor, University of Arizona, 1978-1985
• Scientific Staff, Medical Research Council Cell Biophysics Unit, 1976-1978
• Postdoctoral Fellow, Kings College, University of London, 1973-1976

Education

• Postdoctoral, King's College, London, United Kingdom, 1973-1978
• Ph.D., Brandeis University, Waltham, Mass., 1969-1973
• B.A., University of Colorado, Boulder, Colo., 1964-1969

Research Interests & Funding

The goal of the research in my laboratory is to determine the detailed molecular mechanism of how myosin motor proteins convert the free energy from ATP hydrolysis into movement and work. There are 40 genes for myosin in the human genome, 10 code for myosins in muscle and the other 30 are involved in either the movement or production of tension in various non muscle cells and organs. Defects in myosin motor function can produce such diverse affects as cardiac failure, deafness, blindness and neurological abnormalities. Non muscle myosins have also contributed enormously to our basic understanding of the molecular mechanism of myosin function. Work from my laboratory has been fundamental in determining the important roles of phosphate and ADP dissociation with respect to the powerstroke and shortening velocity of actomyosin. A sabbatical in John Trinick's laboratory sponsored by a Fogarty international fellowship resulted in an extensive collaboration which combined the rapid kinetic methods from my laboratory with the em expertise in Trinick's laboratory to develop various approaches to time resolved electron microscopy, which have been utilized in our work and by the wider scientific community. My laboratory has been funded by NIH and various private foundation grants (MDA, AHA, ACS) since I became an independent investigator. This is a truly exciting time in the molecular motors field as we now have the technology and insight to truly understand function at the molecular level.

Recent Publications:

*Song, CF., Sader, K., White, H., Kendrick-Jones, J. and Trinick, J. Nucleotide dependent shape changes in the reverse direction motor, myosin VI. (2010) Biophys J. in press - accepted for publication Sept. 9, 2010.

*Nicholson, W., White, H. and Trinick, J. An approach to automated acquisition of cryoEM images from lacey carbon grids. J Struct. Biol. 2010. doi:10.1016/j.jsb.2010.08.014

Ahmed Houmeida, David H. Heeley, Betty Belknap, and Howard D. White (2010). Mechanism of regulation of native cardiac muscle thin filaments by rigor cardiac myosinS1 and calcium. J. Biol. Chem. electronic publication Aug. 3, 2010.

Oke OA, Burgess SA, Forgacs E, Knight PJ, Sakamoto T, Sellers JR, White H, Trinick J. (2010). Influence of lever structure on myosin 5a walking. PNAS 107, 2509-2514.

Baboolal TG, Sakamoto T, Forgacs E, White HD, Jackson SM, Takagi Y, Farrow RE, Molloy JE, Knight PJ, Sellers JR & Peckham M. (2009). The SAH domain extends the functional length of the myosin lever. PNAS 106, 22193-22198.

Xu S, White HD, Offer GW, Yu LC. (2009). Stabilization of helical order in the thick filaments by blebbistatin: further evidence of coexisting multiple conformations of myosin. Biophys J. 96. 3673-3681.

Forgacs E, Sakamoto T, Cartwright S, Belknap B, Kovacs M, Toth J, Webb MR, Sellers JR & White HD. (2009). Switch 1 Mutation S217A Converts Myosin V into a Low Duty Ratio Motor. J Biol Chem. 284, 2138-2149.

Sakamoto T, Webb MR, Forgacs E, White HD & Sellers JR. (2008). Direct observation of the mechanochemical coupling in myosinVa during processive movement. Nature 455, 128-132.

Forgacs E, Cartwright S, Sakamoto T, Sellers JR, Corrie JET, Webb MR & White HD. (2008). Kinetics of ADP dissociation from the trail and lead heads of actomyosin V following the power stroke. J Biol Chem. 283, 766-773.

White HD, Ashcroft AE. (2007). Real-time measurement of myosin-nucleotide noncovalent complexes by electrospray ionization mass spectrometry. Biophys J. 93, 914-919.

Forgacs E, Cartwright S, Kovács M, Sakamoto T, Sellers JR, Corrie JE, Webb MR, White HD. (2006). Kinetic mechanism of myosinV-S1 using a new fluorescent ATP analogue. Biochemistry. 45, 13035-13045.

Heeley DH, Belknap B, White HD (2006) Maximal activation of skeletal muscle thin filaments requires both rigor myosin S1 and calcium. J Biol Chem. 281:668-76.

*Available at www.contractility.org

FUNDING:

1. "Electron Cryo-microscopy of Acto-S1 ATPase Intermediates, NIH EB00209 This grant supports work to determine the structure and function of actomyosin ATPase intermediates using site directed mutagenesis, rapid enzyme kinetics and time-resolved electron microscopy

2. "Mechanism of Thin Filament Regulation of Cardiac Actomyosin ATP Hydrolysis", NIH HL84604. This grant supports a study of the mechanism of thin filament regulation of cardiac actomyosin ATP hydrolysis.