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Danny Manor completed his undergraduate studies in Biochemistry in 1982 at Tel Aviv University in Israel and received his PhD in Anatomy, Structural Biology and Biophysics from the Albert Einstein College of Medicine (NY) in 1989. Dr. Manor held a postodctoral position in the Department of Physics at the City University of New York, where he applied biophysical approaches for the study of 'visual pigments' and 'GTP-binding proteins'.
In 1992, Dr. Manor moved to the Department of Pharmacology at Cornell University in Ithaca (NY) where he studied the role of small GTP-binding proteins in malignant transformation. After receiving a faculty position at Cornell's Division of Nutritional Science, his studies diversified to include molecular bases of cancer prevention and vitamin E biology.
Danny Manor joined the Department of Nutrition in the School of Medicine at Case Western Reserve University as an Associate Professor in 2006. His research work has been funded by the American Cancer Society (ACS), the National Cancer Institute (NCI), and the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK).
B.Sc. (Biochemistry) | 1982
Tel Aviv University (Israel)
Ph.D. (Anatomy, Structural Biology & Biophysics) | 1989
Albert Einstein College of Medicine (New York)
Our research interests can be divided to two areas:
(1) understanding the signal transduction pathways that regulate normal cell growth and that are disrupted by oncogenic mutations and,
(2) understanding the molecular mechanisms by which some chemo-preventative agents offer protection from cancer ('molecular prevention').
Research Project I: Signal transduction pathways that regulate cell growth
We are studying how proliferative signaling pathways are regulated in normal cells, and how they are perturbed in particular cancers. We focus on the Dbl family of proto-oncogenes that transduce signals from cell surface factors receptors to the small GTP binding proteins Cdc42, Rac and Rho.
(1) How is the activity of proto-Dbl regulated in normal (untransformed) cells?
The upstream events that lead to activation of Dbl- like exchange factors are unknown at present. We seek to identify the molecules that functionally 'connect' between the exchange factors and cell surface receptors, and how these regulate Dbl's biochemical activity.
(2) What downstream pathway(s) and effectors contribute to Dbl transformation?
Presently, little is known regarding how targets of small GTP-binding proteins regulate cell growth (and transformation). We aim to delineate the downstream cascades that respond to Dbl signaling, decipher their biochemical activity, and, most importantly, understand their contribution to Dbl- induced transformation.
Research Project 2: Biological activities of vitamin E
Vitamin E (tocopherol) is a lipid soluble antioxidant that offers protection against several 'oxidative stress' -related pathologies (cardiovascular disease, neuronal degeneration, inflammation). Vitamin E supplementation also inhibits (and, to some extent, reverses) tumor formation in animal cancer-models.
(1) What are the functions of vitamin E binding proteins?
(2) Does vitamin E function in modulating gene expression?
A few lines of evidence suggest that the physiological functions of vitamin E involve novel activities, such as stimulation of signaling cascades and modulation of transcriptional events. We aim to characterize the genomic and metabolic activities of vitamin E, utilizing expression- profiling and cell-biological approaches.
Gupta M, Kamynina E, Morley S, Chung S, Muakkassa N, Wang H, Brathwaite S, Sharma G, Manor D. (2013) Plekhg4 is a novel Dbl family guanine nucleotide exchange factor protein for rho family GTPases. J. Biol. Chem.; 288: 14522-30.
Ulatowski L, Manor D. (2013) Vitamin E trafficking in Neurologic Health and Disease. Ann. Rev. Nutrition. 33: 87-103.
Ulatowski L, Manor D. (2012) Vitamin E status in Niemann-Pick type C Disease. Diet and Nutrition in Dementia and Cognitive Decline (Elsevier). In press.
Ulatowski L, Dreussi C, Noy N, Barnholtz-Sloan J, Klein E, Manor D. (2012) Expression of the α-tocopherol transfer protein gene is regulated by oxidative stress and common single-nucleotide polymorphisms. Free Radic Biol Med.; 53: 2318-26. PMCID: PMC3612136
Miller GW, Ulatowski L, Labut EM, Lebold KM, Manor D, Atkinson J, Barton CL, Tanguay RL, Traber MG. (2012) The α-Tocopherol Transfer Protein Is Essential for Vertebrate Embryogenesis. 2012 PLoS One 7(10): e47402. PMCID: PMC3471827
Bardowell SA, Duan F, Manor D, Swanson JE, Parker RS. (2012) Disruption of mouse cytochrome p450 4f14 (Cyp4f14 gene) causes severe perturbations in vitamin E metabolism. J Biol Chem.; 287: 26077-86. PMCID: PMC3406691
Traber MG, Manor D. (2012) Vitamin E. Adv Nutr.; 3(3): 330. PMCID: PMC3649464
Bardowell SA, Duan F, Manor D, Swanson JE, Parker RS. (2011) “Disruption of mouse cytochrome p450 4f14 (Cyp4f14 gene) causes severe perturbations in vitamin E metabolism.” (2011) J Lipid Res.; 52(7): 1400-10. PMID: 21550990.
Ulatowski L, Parker R, Davidson C, Yanjanin N, Kelley TJ, Corey D, Atkinson J, Porter F, Arai H, Walkley SU, Manor D. (2011) Altered vitamin E status in Niemann-Pick type C disease. (2011) J Lipid Res.; 52(7): 1400-10. PMID: 21550990.
Thakur V, Morley S, Manor D. (2010) Hepatic a-tocopherol transfer protein (TTP): ligand-induced protection from proteasomal degradation. Biochemistry; 49(43): 9339-44. PMID: 20828164.
Morley S, Thakur V, Danielpour D, Parker R, Arai H, Atkinson J, Barnholtz-Sloan J, Klein E, Manor D. (2010) Tocopherol transfer protein sensitizes prostate cancer cells to vitamin E. J. Biol. Chem.; 285(46): 35578-89. PMID: 20826775.
Atkinson J, Manor D, Parker R. (2010) "Vitamin E" in Encylopedia of Biological Chemistry (W. Lennarz, M. Lane, P. Modrich, J. Dixon, E. Carafoli, J. Exton, & D. Cleveland, Eds.); Elsevier. (invited book chapter).
Kayden HJ and Manor D. (2010) Vitamin E, alpha Tocopherol Transfer Protein and Ataxia with Vitamin E Deficiency. Encyclopedia of Movement Disorders (K. Kompoliti & L. Verhagen, Eds.); Elsevier. (invited book chapter).
Zhang WX, Frahm G, Morley S, Manor D, Atkinson J. (2009) Effect of bilayer phospholipid composition and curvature on ligand transfer by the alpha-tocopherol transfer protein. Lipids; 44(7): 631-41. PMID: 19458973.
Morley S, Cacchini M, Zhang W, Virgulti A, Noy N, Atkinson J, Manor D. (2008) Mechanisms of ligand transfer by the hepatic tocopherol transfer protein. J Biol Chem; 283(26): 17797-804. PMID: 18458085.
Valastyan S, Thakur V, Johnson A, Kumar K, Manor D. (2008) Novel transcriptional activities of vitamin E: inhibition of cholesterol biosynthesis. Biochemistry; 47: 744-52. PMID: 18095660
Manor D, Morley S. (2007) The alpha-tocopherol transfer protein. Vitam. Horm.; 76: 45-65. PMID: 17628171
Kamynina E, Kaupinnen K, Duan F, Muakkassa N, Manor D. (2007) Regulation of the proto-oncogeneic Dbl by ubiquitin-mediated proteasomal degradation. Molec. Cell. Biol.; 27(5): 1809-22. PMID: 17178836
Morley S, Wagner J, Kauppinnen K, Sherman M, Manor D. (2007) Requirement for Akt-mediated survival signaling in cell transformation by the dbl oncogene. Cell Signal; 19(1): 211-8. PMID: 16916597
Qian J, Atkinson J, and Manor D. (2006) Biochemical consequences of heritable mutations in the alpha-tocopherol transfer protein. Biochemistry; 45: 8236-42. PMID: 16024914
Nava P. Cecchini M. Chirico S. Gordon H. Morley S. Manor D. Atkinson J. (2006) Preparation of fluorescent tocopherols for use in protein binding and localization with the alpha-tocopherol transfer protein. Biochemistry; 14(11): 3721-36. PMID: 16481173
Morley S, Cross V, Cecchini M, Nava P, Atkinson J, Manor D. (2006) Utility of a fluorescent vitamin E analogue as a probe for tocopherol transfer protein activity. Biochemistry; 45: 1075-81. PMID: 16430203
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