Larry L. David, Ph.D. (1986, Oregon Health & Science U.)
Research InterestsCataracts result from any opacification of the normally clear lens of the eye. Since cataracts are a leading cause of blindness, studies determining the cause of cataract are an active area of vision research. My interest is in the changes occurring in the structural proteins of the lens when cataracts form. These structural proteins are called crystallins. Crystallins are some of the oldest proteins found in the body, since ones found in the center of the lens were synthesized before birth and remain with us for our entire lives. Due to their age, these proteins undergo extensive modifications, including proteolytic cleavage, deamination, phosphorylation, and oxidation. The challenge in this research is to distinguish between normal age related modifications and unique modifications causing cataract. To do this I perform two-dimensional electrophoresis to separate the crystallins and then analyze their structure using mass spectrometry. Measurement of the molecular mass of the crystallins allows an unambiguous identification of their modifications. Once the modifications unique to crystallins from cataractous lenses are known, it will be possible to model how the alterations cause these proteins to lose their normal transparency. Hopefully, this information will be used to help develop agents to slow the rate of cataract formation. Mass spectrometric analysis is also useful to identify and analyze proteins in other research projects. Two of my collaborative projects include identification of phosphorylation sites in transcription factors and identification of proteins in oral bacteria.
My future interest is in the growing field of proteomics, which uses mass spectrometry to both identify proteins and quantify changes in their relative abundance during disease. This field becomes increasingly important as new genes are sequenced and a complete database of all proteins found in humans becomes available.
National Institutes of Health
Representative PublicationsShibatani T, David LL, McCormack AL, Frueh K, Skach WR. Proteomic analysis of mammalian oligosaccharyltransferase reveals multiple subcomplexes that contain Sec61, TRAP, and two potential new subunits.Biochemistry. 2005;44(16):5982-92.
Searle BC, Dasari S, Wilmarth PA, Turner M, Reddy AP, David LL, Nagalla SR. Identification of protein modifications using MS/MS de novo sequencing and the OpenSea alignment algorithm. J Proteome Res. 2005;4(2):546-54.
Wilmarth PA, Riviere MA, Rustvold DL, Lauten JD, Madden TE, David LL. Two-dimensional liquid chromatography study of the human whole saliva proteome.J Proteome Res. 2004 Sep-Oct;3(5):1017-23.
Duncan MK, Xie L, David LL, Robinson ML, Taube JR, Cui W, Reneker LW. Ectopic Pax6 expression disturbs lens fiber cell differentiation. Invest Ophthalmol Vis Sci. 2004;45(10):3589-98.
Wilmarth PA, Taube JR, Riviere MA, Duncan MK, David LL. Proteomic and sequence analysis of chicken lens crystallins reveals alternate splicing and translational forms of beta B2 and beta A2 crystallins. Invest Ophthalmol Vis Sci. 2004;45(8):2705-15.