Primary Department Affiliation: Vision Sciences
Primary Research Area: Neurodegeneration and Neurodegenerative Disorders
Systems Neuroscience and Vision
My laboratory works on the physiology and biophysics of photoreceptors, the retinal cells which convert light energy into electrochemical signals. By studying the properties of rod and cone cells one can understand how the responses of these nerve cells shape and influence human visual behavior. We use isolated retinal tissue from normal and diseased animals to directly measure the electronic response of photoreceptors to light.
Transgenic animal models of retinal degeneration provide an opportunity to investigate precisely how photoreceptor response properties are altered in physiologically challenging environments. By studying diseased tissues we hope to gain new understanding of normal phototransduction mechanisms as well as learn about the progressive loss of photoreceptor signaling ability in retinal diseases.
Other experiments are aimed at developing novel therapies; these may involve the insertion of new genes targeted specifically at the rod photoreceptors. We are exploring the differences between rod and cone phototransduction and are seeking to identify the key molecular components which determine the electrical response properties.
McKeown, AS, Kraft, TW, & MS Loop (2015). Increased visual sensitivity following periods of dim illumination. Invest Ophthalmol Vis Sci 56:1864-1871; published February 19, 2015, doi:10.1167/iovs.14-15958
Sarfare, S.S., McKeown, A.S., Messinger, J.D., Wei, H-J., Rubin, G.S., Kraft, T.W., & S.J. Pittler. (2014) Overexpression of rod photoreceptor glutamic acid rich protein 2 (GARP2) increases gain and slows recovery in mouse retina. Cell and Communication Signaling. 12(1):67.
Berbari, NF, Malarkey, EB, Zaki, SM, Yazdi, ZR, McNair, AD, Croyle, MJ, Kraft, TW, Yoder, BK (2014) Hippocampal and cortical primary cilia are required aversive memory in mice (ePub Sep 3, 2014) Plos One 9 (9) e106576.
Ward, ME, Taubes, A, Miller, BL, Chen, R, Sephton, CF, Gelfand, JM, Boscardin, J, Martens, LH, Seeley, WW, Yu, G, Herz, J, Filiano, A, Roberson, E, Kraft, TW, Farese, RV Jr, Green, A, Gan, L (2014) Early retinal neurodegeneration and impaired Ran-mediated nuclear import of TDP-43 in progranulin-deficient FTLF. J Exp Med 211:1937-1945.
McKeown, AS and Kraft, TW (2014) Adaptive potentiation in rod photoreceptors. J. Gen. Physiol. 143 (6), 733-743. PMID: 24821966
F Crittenden, H Thomas, CM Ethen, ZL Wu, D Chen, TW Kraft, J Parant, CN Falany (2014) Inhibition of SULT4A1 Expression Induces Up-regulation of Phototransduction Gene Expression in 72 Hours Post Fertilization Zebrafish Larvae. Drug Metab Dispos dmd.114.057042; epub Feb 19, 2014, doi:10.1124/dmd.114.057042
Reish, NJ, Maltare, A, McKeown, AS Laszczyk, AM, Kraft, TW, Gross, AK, & GD King (2013) The age-regulating protein klotho is vital to sustained retinal function. Invest Ophthalmol Vis Sci.54:6675–6685. DOI:10.1167 iovs.13-12550 http://www.ncbi.nlm.nih.gov/pubmed/24045987
Zhang, Q-X., Zhang, Y., Lu, R-W., Li, Y-C., Pittler, S.J. Kraft, T.W., and X-C.Yao (2012) Comparative intrinsic optical signal imaging of wild-type and mutant mouse retinas. Optics Express 20:7646-7654. doi: 10.1364/OE.20.007646. PMID: 22453443.
Zhang, Y., Rubin, G. R., Fineberg, N., Huisingh, C., McGwin, G., Pittler, S. J. & Kraft, T. W. (2012) Age-related ERG changes in Cngb1-X1 Knockout mice: Prolonged Cone Survival. Documenta Ophthalmologica. 124 (3) 163-175. Epub 2012 Feb 26 PMID: 22367173.
McKeown, A.S. and Kraft, T.W. (2013). A new form of photoreceptor Light Adapataion: Enhanced Current Following Illumination. Invest. Ophthalmol. Vis. Sci. Suppl. 2461 (Poster).
McKeown, A.S., Sarfare, S.S., Pittler, S.J., and Kraft, T.W. (2012) Photoransduction Gain is Increased in Rods Overexpressing GARP2. Invest. Ophthalmol. Vis. Sci. Suppl. (poster).
Pittler, S.J., McKeown, A.S., Kraft, T.W., Zhang, Y. (2012) Rod Photoreceptor Expression of an N-terminal Truncated Cngb1a β-subunit in Cngb1-X1 knockout Mice Rescues Structure and Function. Invest. Ophthalmol. Vis. Sci. Suppl. (poster).
Timothy W. Kraft, Associate Professor, Department of Vision Sciences and Scientist in the Vision Science Research Center (VSRC). He received his undergraduate degree in biology from M.I.T. and a Ph.D. (1985) in Physiology from the University of Minnesota in Minneapolis. His research into the neurobiology of color vision began at M.I. T. and shifted to primate retinal tissue during his postdoctoral years at Stanford and the Ophthalmology Department at the University of California at San Francisco. That work included the first electrophysiologic recordings from individual human rod and cone photoreceptors. His association with Ophthalmology Departments at UCSF and as a former Assistant Professor in the Department of Ophthalmology at UAB, have lead him to incorporate the pathologies of photoreceptor degeneration and acquired color vision losses into his studies of the physiology of retinal signal processing.