John D. Simon
Professor Executive Vice President and Provost
Madison Hall (434) 924-2362
- Awards & Honors
Melanin is found throughout the human body – skin, eye, brain, hair, and inner ear – yet its molecular structure remains elusive. The pigment is generally categorized by two distinct classes, pheomelanin (red) and eumelanin (black), and although they share a common origin to their synthesis, they are differentiated by specific molecular reactions occurring early in pigment production. One can find pure eumelanin throughout nature, thereby enabling the quantification of its chemical properties, but pure pheomelanin is commonly observed in conjunction with eumalnin and rarely makes up more than ~25% of the total melanin present. Understanding the factors controlling the relative abundance of the two pigments has become increasingly important because epidemiological studies of skin and ocular cancers suggests that increasing relative proportions of pheomelanin correlate with increased risk factors for these diseases. Consequently, there has been a significant effort to elucidate the chemistry of pheomelanin in order to determine whether the pigment plays a causative role in these cancers and if so, by what mechanism(s). We have used the technique of photoemission electron microscopy (PEEM) to determine surface properties of intact melanosomes,and have recently established that the surface photoionization threshold of pheomelanin is lower than that of eumelanin, supporting the hypothesis that the photoactivation of oxygen by pheomelanin in the UV-A could be a contributing mechanism to UV-induced cancers. A complementary study of intact human melanosomes isolated from different colored irides reveals that the absorption coefficient of the melanosome decreases with increasing pheomelanin content, suggesting the epidemiological data may simply result from an increased exposure of the underlying tissues to UV light. We are currently using PEEM to determine the absorption spectra of intact melanosomes throughout the UV region.
Preservation of soft-tissue in fossils is rare because organic material readily decomposes leaving few traces of its previously complex structures. Resistance to degradation occurs more frequently when structures are highly cross-linked and insoluble in water and melanins meet these criteria. The presence of melanin in the fossil record has been the subject of recent publications. Studies of fossil feathers provide visual evidence of structures commonly associated with melanosomes, organelle like structures containing melanin pigment, and indirect chemical methods confirm the presence and density of melanin distribution using trace metals associated with the structures in long extinct organisms. In collaboration with Dr. Phil Wilby (British Geological Survey) and Dr. Shosuke Ito (Fujita Health University), we are examining fossilized ink sacs from the Jurassic period. Using a variety of analytical and chemical techniques, many involving collaborations with other scientists around the world, we are providing chemical evidence for the existence of the melanin pigment in the fossil record, and are comparing its chemical properties to phylogenic related species present today.
A variety of experimental techniques are commonly used to quantify the binding between nanoparticles and proteins. We are currently comparing the capacity and association constant associated with the binding of chymotrypsin to poly-acrylate coated gold nanoparticles determined by a range of techniques – fluorescence quenching, optical absorption and circular dichroism spectroscopy, isothermal calorimetry, gel electrophoresis. While collectively the data reveal a binding capacity and constant for this particular system of ~7 and ~2 x 106 M-1, respectively; the actual values vary somewhat among the individual techniques, and not all techniques are able to provide insight into both capacity and binding constant. We are exploring the limitations of certain approaches and how the assumptions made in deriving the desired information from the data affect the accuracy of the analysis. We are extending these studies to related protein/nanostructure systems.
The Effect of Dehydration on the Absorption Properties of Intact Melanosomes, Erica Lin, Dana N. Peles, Photochemical and Photobiological Sciences, 11, 687 – 691 (2012)
The UV-Absorption Spectrum of Human Iridal Melanosomes: A New Perspective on the Relative Absorption of Eumelanin and Pheomelnain and its Consequences, Dana N. Peles, John D. Simon, Photochemistry and Photobiology, 88, 1378–1384 (2012).
Direct Chemical Evidence for Undegraded Eumelanin Pigment from the Jurassic Period, Keely Glass, Shosuke Ito, Philip R. Wilby, Takayuki Sota, Atsushi Nakamura, Clifford R. Bowers, Jakob Vinther, Suryendu Dutta, Roger Summons, Derek E. G. Briggs, Kazumasa Wakamatsu, John D. Simon, Proceedings of the National Academy of Science USA, 109 10218-10223 (2012).
Insights into Copper Association with Neuropeptides using Isothermal Calorimetry. Hong, L and Simon, JD. Metallomics – themed issue on Metals in Neurodegenerative Diseases. 3, 262–266 (2011).
The red and the black. Simon JD, Peles DN. Acc Chem Res. 43:1452-60 (2010).