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Thomas Angel, Ph. D., Postdoctoral Fellow

Research interests:

G protein coupled receptors, structural biology and signal transduction


Field of study:

Biochemistry and Signal Transduction


Selected recent publications:

• Angel, T.E., P.C., Kraft, and E.A. Drats, Metarhodopskin-II stabilization by crosslinked Gtalpha C-terminal peptides and implications for the mechanism of GPCR-G protein coupling. Vision Res, 2006. 46(27): p.4547-55.
• Piscitelli, C.L., Angel, T.E., Bailey, B.W., Hargrave, P., Dratz, E.A., and Lawrence, C.M. (2006) Equilibrium between metarhodopsin-I and metarhodopsin-II is dependent on the conformation of the third cytoplasmic loop, J Biol Chem 281 6813-6825.

Grzegorz Bereta, MSc, Research Associate

Research interests:

Regulation of activity of retinal guanylate cyclase

Field of study:

Molecular Biology and Biochemistry

Selected recent publications:

• Golczak M, Maeda A, Bereta G, Maeda T, Kiser P, Hunzelmann S, von Lintig J, Blaner WS, Palczewski K. Metabolic basis of visual cycle inhibition by retinoid and non-retinoid compounds in the vertebrate retina. J Biol Chem. 2008 Jan 14
• Stephen R, Bereta G, Golczak M, Palczewski K, Sousa MC. Stabilizing function for myristoyl group revealed by the crystal structure of a neuronal calcium sensor, guanylate cyclase-activating protein 1. Structure. 2007 Nov;15(11):1392-402

Zhiqian Dong, MD, PhD

Research interests:

Molecular and genetic studies of neurodegenerative diseases and brain tumors

Field of study:

Molecular biology; Histopathology

Selected recent publications:

• Yuan J, Dong Z, Guo JP, McGeehan J, Xiao X, Wang J, Cali I, McGeer PL, Cashman NR, Bessen R, Surewicz WK, Kneale G, Peteren RB, Gambetti P, Zou WQ. Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions. Cell Mol Life Sci 2008 Jan 15 [Epub ahead of print]
• Dong Z, Pang JS, Ng MH, Poon WS, Zhou L, Ng HK. Identification of two contiguous minimally deleted regions on chromosome 1p36.31-p36.32 in oligodendroglial tumours. Br J Cancer 2004; 91(6): 1105-11.
• Pang JC, Dong Z, Zhang R, Liu Y, Zhou LF, Chan BW, Poon WS, Ng HK. Mutation analysis of DMBT1 in glioblastoma, medulloblastoma and oligodendroglial tumors. Int J Cancer 2003; 105(1): 76-81.
• Dong ZQ, Pang JC, Tong CY, Zhou LF, Ng HK. Clonality of oligoastrocytomas. Human Pathol 2002; 33(5): 528-35.

Anna Goc, PhD, Postdoctoral Fellow

Research interests:

Proteins of rod outer segment involved in the visual transduction system

Field of study:

Molecular biology and biochemistry

Selected recent publications:

• W. Dabros, A. Goc, B. Turyna, A.M. Kordowiak: Influence of vanadyl sulphate [VOSO4] on biochemical activity and morphology of control and streptozotocin-diabetic rat liver Golgi complexes, Pol. J. Pathol. 2004; 55: 25-32.
• A.M. Kordowiak, A. Goc, E. Drozdowska, B. Turyna, W. Dabros: Sodium orthovanadate exerts influence on liver Golgi complexes from control and streptozotocin-diabetic rats. J. Inorg. Biochem. 2005; 99: 1086-1089.
• Anna Goc: Biological activity of vanadium compounds. Cent. Eur. J. Biol. 2006; 1: 314-332.
• Pharmacology Retreat Geneva-on-the-Lake, Cleveland 25-26 October 2007 ( A. Goc, K. Palczewski, Purification of native transducin and cGMP phosphodiesterase - two main peripheral proteins of disk membranes of rod cells.

Marcin Golczak, PhD, Research Associate

Research interests:

Molecular biology of vision, Retinoid metabolism


Field of study:

Biochemistry

Selected recent publications:

• Isken A, Golczak M, Oberhauser V, Hunzelmann S, Driever W, Imanishi Y, Palczewski K, and von Lintig J. RBP4 Disrupts Vitamin A Uptake Homeostasis in a STRA6-Deficient Animal Model for Matthew-Wood Syndrome. Cell Metabolism, in press
• Golczak M, Maeda A, Bereta G, Maeda T, Kiser P, Hunzelmann S, von Lintig J, Blaner WS, Palczewski K. Metabolic basis of visual cycle inhibition by retinoid and non-retinoid compounds in the vertebrate retina. J Biol Chem. 2008 Jan 14;
• Golczak M, Imanishi Y, Kuksa V, Maeda T, Kubota R, Palczewski K. Lecithin:retinol acyltransferase is responsible for amidation of retinylamine, a potent inhibitor of the retinoid cycle. J Biol Chem. 2005 Dec 23;280(51):42263-73
• Golczak M, Kuksa V, Maeda T, Moise AR, Palczewski K. Positively charged retinoids are potent and selective inhibitors of the trans-cis isomerization in the retinoid (visual) cycle. Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8162-7.

Jingwei Huang, PhD, Senior Research Associate

Research interests:

Medically and biologically important proteins examined by X-ray crystallography


Field of study:

Structural biology, especially protein crystallography

Selected recent publications:

• Huang, J., Lipscomb, W.N. (2006) T-state active site of aspartate transcarbamylase: crystal structure of the carbamyl phosphate and L-alanosine ligated enzyme, Biochemistry, 45, 346-352.
• Huang, J., Lipscomb, W.N. (2004) Aspartate transcarbamoylase (ATCase) of Escherichia coli: A new crystalline R state bound to PALA, or to product analogues phosphate and citrate, Biochemistry, 43, 6415-6421.
• Huang, J., Lipscomb, W.N. (2004) Products in the T state of aspartate transcarbamoylase: Crystal structure of phosphate and N-carbamoyl-L-aspartate ligated enzyme, Biochemistry, 43, 6422-6426.
• Pace, H.C., Hodawadekar, S.C., Draganescu, A., Huang, J., Bieganowski, P., Pekarsky, Y., Croce, C.M., Brenner C. (2000) Crystal Structure of the worm NitFhit Rosetta Stone protein revels a Nit tetramer binding two Fhit dimers, Current Biology, 10, 907-917.

Beata Jastrzebska, PhD, Senior Fellow

Research interests:

Structural biology of macromolecules.

Field of study:

Biochemistry and Signal Transduction

Selected recent publications:

• B. Jastrzebska, T. Maeda, L. Zhu, D. Fotiadis, S. Filipek, A. Engel, R.E. Stenkamp, K. Palczewski, (2004). Functional characterization of rhodopsin monomers and dimers in detergents. J. Biol. Chem., 279: 53828-53839.
• B. Jastrzebska, D. Fotiadis, GF Jang, A. Engel, R.E. Stenkamp, K. Palczewski, (2006). Functional and structural characterization of rhodopsin oligomers. J. Biol. Chem., 281: 11917-11922.
• D. Fotiadis, B. Jastrzebska, A Philippsen, DJ Muller, K. Palczewski, A. Engel, K. Palczewski, (2006). Structure of rhodopsin dimer: a working model for G-protein-coupled receptors. Curr. Opin. Struct. Biol., 2: 252-259.
• M.R. Whorton, B. Jastrzebska, P.S. Park, D. Fotiadis, A. Engel, K. Palczewski, R.K. Sunahara (2008). Efficient coupling of transducin to monomeric rhodopsin in a phospholipid bilayer. J Biol Chem., 283:4387-94.

Philip Kiser , PharmD, Graduate Student

Research interests:

X-ray crystallographic structure determination of proteins

Field of study:

Pharmacology

Selected recent publications:

• Golczak, M., Maeda, A., Bereta, G., Maeda, T., Kiser, P., Hunzelmann, S., von Lintig, J., Blaner, W. S., and Palczewski, K. (2008) J Biol Chem
• Kiser, P. D., Lodowski, D. T., and Palczewski, K. (2007) Acta Crystallogr Sect F Struct Biol Cryst Commun 63(Pt 6), 457-461
• Matsumoto, M. L., Narzinski, K., Kiser, P. D., Nikiforovich, G. V., and Baranski, T. J. (2007) J Biol Chem 282(5), 3105-3121
• Moise, A. R., Dominguez, M., Alvarez, S., Alvarez, R., Schupp, M., Cristancho, A. G., Kiser, P. D., de Lera, A. R., Lazar, M. A., and Palczewski, K. (2008) Journal of the American Chemical Society 130(4), 1154-1155

Research interests:

X-ray crystallographic structure determination of membrane proteins

Field of study:

G protein signaling and membrane protein physiology  

Selected recent publications:

• Lodowski DT , Pitcher JA, Capel WD, Lefkowitz RJ, Tesmer JJG: Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gβ1γ2. Science 2003, 300: 1256-1262.
• Salom D, Le Trong I, Pohl E, Ballesteros JA, Stenkamp RE, Palczewski K, Lodowski DT. Improvements in G protein-coupled receptor purification yield light stable rhodopsin crystals. Journal of Structural Biology. 2006 Jun 2; [Epub ahead of print]
• Salom D, Lodowski DT, Stenkamp RE, Le Trong I, Golczak M, Jastrzebska B, Harris T, Ballesteros JA, Palczewski K.Crystal structure of a photoactivated deprotonated intermediate of rhodopsin.Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16123-8. Epub 2006 Oct 23.
• Lodowski DT, Salom D, Le Trong I, Teller DC, Ballesteros JA, Palczewski K, Stenkamp RE.Crystal packing analysis of Rhodopsin crystals. J Struct Biol. 2007 Jun;158(3):455-62. Epub 2007 Feb 9.

• Maeda A, Maeda T, Sun W, Zhang H, Baehr W, Palczewski K. Redundant and unique roles of retinol dehydrogenases in the mouse retina. Proc Natl Acad Sci USA. 2007; 104, 19565-19570.
• Maeda A, Maeda T, Imanishi y, Sun W, Jastrzbska B, Hatala DA, Winkens HJ, Hofmann KP, Janssen JJ, Beahr W, Driessen CA, Palczewski K. Retinol dehydrogenase (RDH12) protects photoreceptors from light-induced degeneration in mice.  J. Biol. Chem. 2006; 281, 37697-37704.
• Maeda A, Maeda T, Golczak M, Imanishi Y, Leahy P, Kubota R, Palczewski K. Effects of potent inhibitors of  the retinoid cycle on visual function and photoreceptor protection from light damage in mice. Mol Pharmacology 2006; 70, 1220-1229.
• Maeda A, Maeda T, Palczewski K. Improvements in rod and cone functions in the mouse model of Fundus Albipunctatus after pharmacological treatments with 9-cis-retinal. Invest Ophthal­mol Vis Sci 2006;  47, 4540-4546.

Tadao Maeda, MD, PhD, Instructor

Research interests:

Structure analysis and characterization of rod outer segment proteins of vertebrate photoreceptor cells

Field of study:

Biochemistry of Vision

Selected recent publications:

• Maeda A, Maeda T, Sun W, Zhang H, Baehr W, Palczewski K. Redundant and unique roles of retinol dehydrogenases in the mouse retina. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19565-70. Epub 2007 Nov 28.
• Golczak M, Kuksa V, Maeda T, Moise AR, Palczewski K. Positively charged retinoids are potent and selective inhibitors of the trans-cis isomerization in the retinoid (visual) cycle. Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8162-7. Epub 2005 May 25.
• Maeda T, Lem J, Palczewski K, Haeseleer F. A critical role of CaBP4 in the cone synapse. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4320-7.
• Haeseleer F, Imanishi Y, Maeda T, Possin DE, Maeda A, Lee A, Rieke F, Palczewski K. Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in photoreceptor synaptic function. Nat Neurosci. 2004 Oct;7(10):1079-87. Epub 2004 Sep 26.

Alex Moise, PhD, Instructor

Research interests:

Physiological roles and metabolism of vitamin A and its derivatives.

Field of study:

Molecular biology, biochemistry

Selected recent publications:

• Moise AR, Domínguez M, Alvarez S, Alvarez R, Schupp M, Cristancho AG, Kiser PD, de Lera AR, Lazar MA, Palczewski K. Stereospecificity of retinol saturase: absolute configuration, synthesis, and biological evaluation of dihydroretinoids. J. Am. Chem. Soc. 2008 Jan 30;130(4):1154-5.
• Moise AR, Noy N, Palczewski K, Blaner WS. Delivery of retinoid-based therapies to target tissues. Biochemistry. 2007 Apr 17;46(15):4449-58. Review
• Moise AR, Isken A, Domínguez M, de Lera AR, von Lintig J, Palczewski K. Specificity of zebrafish retinol saturase: formation of all-trans-13,14-dihydroretinol and all-trans-7,8- dihydroretinol. Biochemistry. 2007 Feb 20;46(7):1811-20.
• Moise AR, Golczak M, Imanishi Y, Palczewski K. Topology and membrane association of lecithin: retinol acyltransferase. J. Biol. Chem. 2007 Jan 19;282(3):2081-90.

Debarshi Mustafi, MD/PhD student

Research interests:

Cone cell morphology and function.

Field of study:

Pharmacology

Selected recent publications:

• Li, L., Mustafi, D., Fu, Q., Tereshko, V., Chen, D. L., Tice, J. D., and Ismagilov, R. F., Nanoliter Microfluidic Hybrid Method for Simultaneous Screening and Optimization Validated with Crystallization of Membrane Proteins, Proceedings of the National Academy of Sciences, 2006, 103, 19243-19248
• Adamson, D. N., Mustafi, D., Zhang, J. X. J., Zheng, B., and Ismagilov, R. F., Producing Arrays of Chemically Distinct Nanoliter Plugs via Repeated Splitting in Microfluidic Devices, Lab on a Chip, 2006, 6, 1178 - 1186.
• Tezcan, F. A., Kaiser, J. T., Mustafi, D., Walton, M. Y., Howard, J. B., and Rees, D. C., Nitrogenase Complexes: Multiple Docking Sites for a Nucleotide Switch Protein, Science, 26 August 2005, 1377-1380.

Tivadar Orban, Ph.D., Postdoctoral Scholar

Research interests:

Biochemistry/Biophysics

Field of study:

Guanylate cyclase activating protein-1 activity regulation / Retinosome function

Selected recent publications:

• Orban T., Kalafatis M., Gogonea V. Completed three-dimensional model of human coagulation factor Va. Molecular dynamics simulations and structural analyses. Biochemistry. 2005, 44:13082-90
• Bukys M.A., Orban T., Kim P.Y., Beck D.O., Nesheim M.E., Kalafatis M. The structural integrity of anion binding exosite I of thrombin is required and sufficient for timely cleavage and activation of factor V and factor VIII. J. Biol. Chem. 2006, 281:18569-80
• Bukys M.A., Orban T., Kim P.Y., Nesheim M.E., Kalafatis M. The interaction of fragment 1 of prothrombin with the membrane surface is a prerequisite for optimum expression of factor Va cofactor activity within prothrombinase. Thromb. Haemost. 2008, 99:511-22
• Barhoover, M.A., Orban T., Beck D.O., Bukys M.A., Kalafatis M. Contribution of amino acids 334 and 335 from the factor Va heavy chain to the catalytic efficiency of prothrombinase. Biochemistry (in press)

David Peck , Lab Manager

Mikolaj Piekarski , MPharm, SURP student

Research interests:

Biochemistry of vision, vision circle and also anthracycline antibiotics

Field of study:

Pharmacy

Selected recent publications:

• Marianna Zajac, Przemyslaw Zalewski, Anna Jelinska, Mikolaj Piekarski, Irena Oszczapowicz, Malgorzata Wasowska. "Stability of (N-hexahydroazepi-1-yl)methylenedaunorubicine in alkaline solutions" "Achievements in drug chemistry"congress, Poznan Sep 6-7 2007
• Piekarski M., Ratajczak T., Lesniak M., Snarski J., "Microwave assisted synthesis of new azole derivatives as potential new drugs" Polish Chemical Association congress, Poznan Sep 2005.

Lakshmi Padmavathi Pulagam , Ph.D., Postdoctoral Scholar

Research interests:

Structural Biology and Structure-based drug design.

Field of study:

Molecular biology, Biochemistry and Bioinformatics.

Selected recent publications:

• Pulagam V.L. Padmavathi and HJ-Steinhoff. Conformation of the closed channel state of colicin A in proteoliposomes: An umbrella model. Journal molecular biology 2008, 378:204-214.
• K. Bharati, S. R. Mohanty, P.V.L. Padmavathi, V. R. Rao and T. K. Adhya. Influence of six nitrification inhibitors on methane production in a flooded alluvial soils. Nutrient cycling in agro eco systems 2000, 58:389-394.

Melissa Matosky, Research Assistant, Medical School Student

Satsumi Roos, Research Assistant

Sanae Sakami, Ph.D., Postdoctoral Fellow

Research interests:

Cell biology of the photoreceptor cell

Field of study:

Cell biology

Selected recent publications:

• Sakakibara S, Hiramatsu H, Takahashi Y, Hisatomi O, Kobayashi Y, Sakami S, Saito T, Tokunaga F.  Opsin expression in adult, developing, and regenerating newt retinas. Brain Res Mol Brain Res. 2002; (103) 28-35.
• Sakami S, Hisatomi O, Sakakibara S, Liu J, Reh TA, Tokunaga F.  Downregulation of Otx2 in the dedifferentiated RPE cells of regenerating newt retina.  Brain Res Dev Brain Res.  2005; (155) 49-59.
• Sakami S, Etter P, Reh TA. Activin signaling limits the competence for retinal regeneration from the pigmented epithelium. Mechanisms of Development. 2008;125(1-2):106-16.

David Salom, Ph.D., Scientist

Research interests:

Structure-activity relationship of membrane proteins in general, and GPCRs in particular

Field of study:

Structural biology, pharmacology

Selected recent publications:

• Salom D, Perez-Paya E, Pascal J, & Abad C. "Environment- and sequence-dependent modulation of the double-stranded to single-stranded conformational transition of gramicidin A in membranes". Biochemistry 37, 14279-14291 (1998).
• Salom D , Hill BR, Lear JD, & DeGrado WF. "pH-Dependent tetramerization and amantadine binding of the transmembrane helix of M2 from influenza A virus". Biochemistry 39, 14160-14170 (2000).
• Salom D, Lodowski DT, Stenkamp RE, Le Trong I, Golczak M, Jastrzebska B, Harris T, Ballesteros JA, & Palczewski K. "Crystal structure of a photoactivated deprotonated intermediate of rhodopsin". Proc. Natl. Acad. Sci. USA 103, 16123-16128 (2006).
• Stouffer AL*, Acharya R*, Salom D*, Levine AS, Di Costanzo L, Soto CS, Tereshko V, Nanda V, Stayrook S, & DeGrado WF. "Structural basis for the function and pharmaceutical inhibition of an influenza virus proton channel". Nature 451, 596-599 (2008). *Contributed equally.

Madeline Singer, Student Worker

• Sun W, Gerth C, Maeda A, Lodowski DT, van der Kraak L, Saperstein DA, Heon E, Palczewski K. Novel RDH12 mutations associated with Leber Congenital Amaurosis and Cone-Rod Dysthrophy: Biochemical and Clinical Evaluations. Vision Res. 2007, 47(15): 2055-66.
• Maeda A, Maeda T, Sun W, Zhang H, Baehr W and Palczewski K. Redundant and unique roles of retinol dehydrogenases in the mouse retina. PNAS. 10.1073/pnas.0707477104.
• Chen Y, Guo X, Deng FM, Liang FX, Sun W, Ren M, Izumi T, Sabatini DD, Sun TT, Kreibich G. Rab27b is associated with fusiform vesicles and may be involved in targeting uroplakins to urothelial apical membranes. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14012-14017.
• Sun W, Liu S, Brindley PJ, Mcmanus DP. Bacterial expression and characterization of functional recombinant triosephosphate isomerase from Schistosoma japonicum. Protein Expr Purif. 1999 Dec;17:410-3.

Research Interest:

Structure-function relationships in complex proteins, protein-protein interactions, structural enzymology

Field of Study:

Structural biology, biophysics, biochemistry

• Y. Tsybovsky, H. Donato, N.I. Krupenko, C. Davies, S.A. Krupenko: Crystal structures of the carboxyl terminal domain of rat 10-formyltetrahydrofolate dehydrogenase: implications for the catalytic mechanism of aldehyde dehydrogenases. Biochemistry. 2007; 46: 2917-29.
• Y. Tsybovsky, D.V. Shubenok, Z.I. Kravchuk, S.P. Martsev: Folding of an antibody variable domain in two functional conformations in vitro: calorimetric and spectroscopic study of the anti-ferritin antibody VL domain. Protein Eng. Des. Sel. 2007; 20: 481-90.
• H. Donato, N.I. Krupenko, Y. Tsybovsky, S.A. Krupenko. 10-formyltetrahydrofolate dehydrogenase requires a 4'-phosphopantetheine prosthetic group for catalysis. J. Biol. Chem. 2007; 282: 34159-66.

Research Interest:

Structural biology

Field of Study:

Pharmacology and biochemistry

• Soelaiman S, Jakes K, Wu N, Li C, and Shoham M. (2001) Crystal Structure of Coicin E3: Implications for Cell Entry and Ribosome Inactivation. Molecular Cell.  8:1053-1062.
• Zarivach R, Ben-Zeev E, Wu N, Auerbach T, Bashan A, Jakes K, Dickman K, Kosmidis A, Schluenzen F, Yonath A, Eisenstein M, and Shoham M. (2002) On the Interaction of Colicin E3 with the Ribosome. Biochimie. 84: 447-454.
• Wu N, Macion-Dazard R, Nithianantham S, Xu Z, Vishnivetskiy SA, Gurevich VV, Thibonnier M, and Shoham M. (2006) Soluble mimics of the cytoplasmic face of the human V1-vascular vasopressin receptor bind arrestin2 and calmodulin, Molecular Pharmacology. 70: 249-258.
• Wu N, Hanson SM, Francis DJ, Vishnivetskiy SA, Thibonnier M, Klug CS, Shoham M, Gurevich V. (2006) Arrestin binding to calmodulin: a direct interaction between two ubiquitous signaling proteins.  J. Mol. Bio. Accepted.