Our interests in bioorganic chemistry include activity in organic synthesis as well as protein and lipid biochemistry, structural biology, and analytical biochemistry.

Strong collaborations with active groups in the Canada, the US, and Europe mean that we are directly involved with aspects of vitamin E (tocopherol) biokinetics, intracellular location, the mechanism of action of the tocopherol transfer protein (TTP), and other lipid transfer proteins, as well as proteins that interact with phospholipid membranes.

We have prepared 22 different fluorescent forms of tocopherol some of which have been used to follow intracellular and tissue location of this vitamin. Our newest labels are now being used in 3D-imaging of mice brains to explore the role of vitamin E in neuron and brain health.

We have also designed and synthesized compounds that disrupt the normal oxidative metabolism of tocopherols and may aid in the understanding of the fate of the different forms of vitamin E and the potential of tocotrienols as therapeutics for human health.

Lipid Transfer and Binding Proteins

Every hydrophobic ligand would have trouble moving about the aqueous portion of cells were it not for specific transfer proteins. Transfer proteins exist for retinoids, sterols, fatty acids, phospholipids, cholesterol, vitamin D and, of course, vitamin E (tocopherols). Each ligand has particular biochemistry to which the transfer protein must be attuned.

For instance, the sterol binding proteins (SBP) and ceramide transfer proteins (CERT) are coordinated so that the biosynthesis of both cholesterol and ceramides are controlled together. Since tocopherols are vitamins, there is no necessity for controlling biosynthesis in mammalian tissue, but we, and our collaborators, have shown that the tocopherol transfer protein (TTP) has a critical role to play in transporting tocopherol to particular membranes involved in vesicular traffic (i.e. VLDL secretion from liver cells) or to those membranes that are prone to lipid peroxidation.

We are looking at the features that control the rates of tocopherol delivery to membranes by TTP. To this end we have developed FRET assays using our fluorescent tocopherol derivative NBD-alpha-tocopherol. By varying the phospholipid composition of membrane acceptor, as well as making mutations in the transfer protein, we (along with Dr. Danny Manor, at Case Western Reserve University) have begun to decipher those features necessary for membrane recognition by TTP, and phospholipids that effect efficient transfer. Our most recent work focuses on the role of tocopherol in neurons and astrocytes. Vitamin E deficiency can lead to critical pathologies of the nervous system, especially cerebellar ataxias.

Other proteins of interest include the phosphatidylinositol binding proteins (PITPs) Sec14p (from yeast) and the mammalian orthologues PITPalpha and PITPbeta. Using a fluorescent form of phosphatidylcholine (PC) we are able to show the ability of these proteins to transfer PC to membranes and how the rate of this transfer is affected by membrane curvature and composition. Particularly important are the so-called addressing-lipids called phosphatidylinositol phosphates (PIPs). The oxysterol binding protein (OSBP) is particularly sensitive to the presence of membrane PIPs and we have shown that PI(4)P is extracted from the membrane by OSBP. Current work is exploring the role of sterols in modifying membrane and PIP recognition.

We base our protein experiments on two major techniques. One, mentioned above, is fluorescence energy resonance transfer (FRET), and the other is called surface plasmon resonance (SPR). In brief, this is a surface adsorption technique that allows us to adsorb phospholipid vesicles onto a sensor chip. We can then measure the rates of protein association and dissociation with the tethered vesicles. By analyzing specific protein mutants and by changing vesicle phospholipid composition we learn great deal about how the protein can recognize membranes, and deliver or extract ligands. All of this work lends support to the proposed mechanism(s) of these protein in vivo.

Synthesis of lipid-based probes of protein-membrane interactions

About half of our research group performs organic synthesis. We design and prepare new compounds to investigate the function of proteins that interaction with phospholipid membranes.

We remain active in the organic synthesis of tocopherols and tocotrienols, and other hydrophobic compounds as tools for biochemical research. This inlcudes a number of efforts such as:

• membrane-spanning bola-phospholipids as probes of phospholipid transfer protein action
• phospholipid biomolecular probes and bioconjugates
  • fluorescent phospholipids
  • conformationally restricted phospholipids
  • photocleavable and redox active bola-phospholipids
  • biotin tagged lipid (photo)affinity labels

2023

Matthew Chen, Michael Ghelfi, Vansh Mehta, Jia-Fei Poon, Stephen Valentino, Michaela Stamper, Anirudh Muralidharan, Hamza Tariq, Elizabeth Zunica, Lynn Ulatowski, Stacey Chung, Mark Cameron, Cheryl Cameron, Derek Pratt, Jeffrey Atkinson, Carrie Finno, Danny Manor. For submission to Antioxidants (Dec 2023)

Sean Wilson, Candace Panagabko, Tayo Laleye, Morgan Robinson, Samuel Jagas, David Bowman, Jeffrey Atkinson. Synthesis of a Photocleavable Bola-Phosphatidylcholine. Bioorg. Med. Chem. 117465 (2023) doi:10.1016/j.bmc.2023.117465.

Valerian E Kagan, Yulia Y Tyurina, Karolina A Mikulska-Ruminska, Deena Damschroder, Alessia Lasorsa, Aleksander A Kapralov, Vladimir A Tyurin, Andrew A Amoscato, Svetlana N Samovich, Haider H Dar, Abu Ramim, Michael W Schmidtke, Georgy K Vladimirov, Margarita A Artyukhova, Ammanamanchi Niyatie, Emma-Kate Baker*, Jim Peterson, Grant M Hatch, Jeffrey Atkinson, Kuhn Bernhard, Robert Wessells, Patrick CA van der Wel, Ivet Bahar, Hulya Bayir, Miriam L. Greenberg. (2022). Anomalous peroxidase is the primary pathogenic target in Barth syndrome. Nature – Metabolism. In-press 2023

Angelo Azzi, Jeffrey Atkinson, Nesrin Kartal Ozerc, Danny Manor, Maria Wallert, Francesco Galli.

Vitamin E discussion forum position paper on the revision of the nomenclature of vitamin E. Free Radic. Biol. Med. 207, 178–180 (2023). doi: 10.1016/j.freeradbiomed.2023.06.029

2022

Lynn Ulatowski, Mikel Ghelfi*, Ryan West*, J. Atkinson, C. J. Finno, and D. Manor. (2022). The tocopherol transfer protein mediates vitamin E trafficking between cerebellar astrocytes and neurons. Journal of Biological Chemistry. 298(3): 101712-101724. http://dx.doi.org/https://doi.org/10.1016/j.jbc.2022.101712

Nicholas Krueger*, Sean Wilson*, Anna Migni, Francesco Galli, Jeffrey Atkinson. (2022). The reactivity of Vitamin E quinones with N-acetyl cysteine. Bioorganic and Medicinal Chemistry.
Awaiting collaborator contributions. Submission for Dec 2023.

2021

Jeffrey Atkinson, Drew Marquardt, Mitchell DiPasquale, Thad Harroun,. (2021). From fat to bilayers: Understanding where and how vitamin E works. Free Radical Biology and Medicine. 176: 73-79. http://dx.doi.org/10.1016/j.freeradbiomed.2021.09.015

2020

Pierre-Christian Violet, Ifechukwude C. Ebenuwa, Yu Wang, Mahtab Niyyati, Sebastian J. Padayatty, Brian Head, Kenneth Wilkins, Stacey Chung, Varsha Thakur, Lynn Ulatowski, Jeffrey Atkinson, Mikel Ghelfi, Sheila Smith, Hongbin Tu, Gerd Bobe, Chia-Ying CCVLiu, David W. Herion, Robert D. Shamburek, Danny Manor, Maret G. Traber, and Mark Levine. Vitamin E sequestration by liver fat in humans.  JCI Insight. 2020;5(1):e133309. https://doi.org/10.1172/jci.insight.133309.

2019

Candace Panagabko, Matilda Baptist, Jeffrey Atkinson. In vitro lipid transfer assays of phosphatidylinositol transfer proteins provide insight into the in vivo mechanism of ligand transfer. BBA Biomembranes 1861, 2019, 619-630.

Mikel Ghelfi, Lucas A. Maddalena, Jeffrey A. Stuart, Jeffrey Atkinson, Thad A. Harrounc, Drew Marquardt. Vitamin E-inspired multi-scale imaging agent. Bioorganic and Medicinal Chemistry Letters. 2019, 29(1), 107-114.

https://doi.org/10.1016/j.bmcl.2018.10.052

Atkinson, D. Marquardt, and T. Harroun. The Behaviour of Vitamin E in Membranes. Invited review in the book and eBook “Vitamin E: Chemistry and Nutritional Benefits” published by The Royal Society of Chemistry, 2019. (in press)

Jeffrey Atkinson, Varsha Thakur and Danny Manor. The tocopherol transfer protein: regulator of vitamin E status. (Invited review) In “Vitamin E in Human Health” Edited by M. Birringer and Peter Weber. Springer 2019. (in press)

2018

Panagabko, M. Baptist, J. Atkinson, In vitro lipid transfer assays of phosphatidylinositol transfer proteins provide insight into the in vivo mechanism of ligand transfer, Biochimica Et Biophysica Acta (BBA) – Biomembranes, (2018) 1861(3) 619-630. https://doi.org/10.1016/j.bbamem.2018.12.003

Luke Taylor, Nick Krueger, Olga Malysheva, Jeffrey Atkinson, Robert S. Parker. ω-Hydroxylation of α-tocopheryl quinone reveals a dual function for cytochrome P450-4F2 in vitamin E metabolism. Bioorganic & Medicinal Chemistry 26 (20), 2018, Pages 5555-5565

https://doi.org/10.1016/j.bmc.2018.10.002

Parthajit Mukherjee, Hasam Madarati, Neale D. Ridgway, Jeffrey Atkinson. Lipid and membrane recognition by the oxysterol binding protein and its phosphomimetic mutant using dual polarization interferometry. Biochimica et Biophysica Acta – Biomembranes.2018,1860(11), 2356-2365. https://doi.org/10.1016/j.bbamem.2018.05.022

2017

Drew Marquardt, Brad J. Van Oosten, Mikel Ghelfi, Jeffrey Atkinson, Thad A. Harroun. Vitamin E Circular Dichroism Studies: Insights to conformational changes induced by the solvent’s polarity. Membranes,2017, 6(4), 56. doi:10.3390/membranes6040056

Lucas A. Maddalena, Mikel Ghelfi, Jeffrey Atkinson^,and Jeffrey A. Stuart. TPP-IOA affects mitochondrial bioenergetics and its protective efficacy in cells is influenced by cellular dependence on aerobic metabolism. BBA-Bioenergetics2017, 1858(1), 73-85. https://doi.org/10.1016/j.bbabio.2016.11.005

2016

Drew Marquardt, Brad J. Van Oosten, Mikel Ghelfi, Jeffrey Atkinson, Thad A. Harroun. Vitamin E Circular Dichroism Studies: Insights to conformational changes induced by the solvent’s polarity. Membranes, 6(4). E56. [PubMed]

Lucas A. Maddalena, Mikel Ghelfi, Jeffrey Atkinson, and Jeffrey A. Stuart. The mitochondria-targeted imidazole substituted oleic acid ‘TPP-IOA’ affects mitochondrial bioenergetics and its protective efficacy in cells is influenced by cellular dependence on aerobic metabolism
BBA-Bioenergetics 2017, 1858 (1), 73-85. [PubMed]

Stacey Chung, Mikel Ghelfi, Jeffrey Atkinson, Robert Parker, Jinghui Qian, Cathleen Carlin, Danny Manor. Regulation of the Hepatic a-Tocopherol Transfer Protein by Vitamin E and Phosphoinositides. J Biol Chem 2016, 291 (33), 17028-17039. [PubMed]

Mikel Ghelfi, Lynn Ulatowski, Danny Manor, Jeffrey Atkinson. Synthesis and characterization of a fluorescent probe for a-tocopherol suitable for fluorescence spectroscopy. Bioorganic & Medicinal Chemistry, 2016, 24(12), 2754-2761. [PubMed]

Matilda Baptist, Candace Panagabko, Shamshad Cockcroft, Jeffrey Atkinson. Ligand and membrane-binding behavior of the phosphatidylinositol transfer proteins PITPα and β. Biochemistry and Cell Biology, 2016, (94) 528-533. [PubMed]

2015

Xiaoling Leng, Jacob J. Kinnun, Drew Marquardt, Mikel Ghefli, Norbert Kučerka, John Katsaras, Jeffrey Atkinson, Thad A. Harroun, Scott E. Feller and Stephen R. Wassall.  Tocopherol is well-designed to protect polyunsaturated phospholipids: md simulations Submitted to Biophysical Journal, 2015

Desiree Bailey; Jeffrey Atkinson; Solomon Fixon-Owoo; Martin C Henman; Graham G Shaw; Karen M Doyle, Brian P Kirby. Hydroxycinnamic acid amide derivatives of polyamines reverse spermine-induced CNS excitation. Pharmacology, Biochemistry and Behavior. [PubMed] 133:57-64, 2015

Baptist, M., Panagabko, C., Nickels, J. D., Katsaras, J., & Atkinson, J. 2,2′-Bis(monoacylglycero) PO₄ (BMP), but not 3,1′-BMP, increases membrane curvature stress to enhance α-tocopherol transfer protein binding to membranes. Lipids. 50(3):323-8, 2015 [PubMed]

2014

Jianfei Jiang, Ahmet  Bakan, Alexandr A Kapralov , Zhentai Huang, Andrew A Amoscato, Venkata K Garapati; Kulakulasooriyag I Ishara, Sunil  K Saxena, Hülya Bayir, Jeffrey Atkinson, Ivet  Bahar, Valerian E Kagan. Designing Inhibitors of Cytochrome c/Cardiolipin Peroxidase Complexes:  Mitochondria-Targeted Imidazole-Substituted Fatty Acids. Free Rad. Biol. Med. 71, 221-230, 2014, [PubMed]

Marquardt D, Williams JA, Kinnun JJ, Kučerka N, Atkinson J, Wassall SR, Katsaras J, Harroun TA. Dimyristoyl Phosphatidylcholine: A Remarkable Exception to α-Tocopherol’s Membrane Presence.  J. Am. Chem. Soc. 2014, 136(1): 203-10. [PubMed]

2013

Julie Goff, Donna Shields, Hong Wang, Erin Skoda, Melissa Sprachman, Peter Wipf , Venkata Krishna Garapati, Jeffrey Atkinson, Barry London, John Lazo, Valerian Kagan, Michael Epperly and Joel S. Greenberger. Evaluation of ionizing irradiation protectors and mitigators using clonogenic survival of human umbilical cord blood hematopoietic progenitor cells. (In Press:  Experimental Hematology, 41(11):957-66 2013, 41(11):957-66. [PubMed]

Marquardt, Drew; Williams, Justin; Kucerka, Norbert; Atkinson, Jeffrey; Wassall, Stephen; Katsaras, John; Harroun, Thad “Tocopherol activity correlates with its location in a membrane: A new perspective on the anti-oxidant Vitamin E.” J. Am. Chem. Soc., 2013, 135 (20), pp 7523–7533.[PubMed]

Bo Li, Jitendra R. Harjani, Nicholas S. Cormier, Hasam Madarati, Jeffrey Atkinson and Derek A. Pratt. Besting Vitamin E: The role of sidechain substitution on the reactivity of naphthyridinol antioxidants in lipid bilayers. J. Amer. Chem. Soc. 135, 1394–1405, 2013. [PubMed]

Galen W Miller, Lynn Ulatowski, Edwin M Labut, Katie M Lebold, Danny Manor, Jeffrey Atkinson, Carrie L Barton, Robert L Tanguay, Maret G Traber. The α-tocopherol transfer protein is essential for vertebrate embryogenesis. PLoS ONE 7(10): e47402. doi:10.1371/journal.pone.0047402. 2013 [PubMed]

2012

 Christine A. McCary, Youngdae Yoon, Candace Panagabko, Wonhwa Cho, Jeffrey Atkinson, and Joan M. Cook-Mills. Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. Biochemical Journal, 2012, 441, 189-198 [PubMed]

2011

 Ulatowski, L., Parker, R., Davidson, C., Yanjanin, N., Kelley, T. J., Corey, D., Atkinson, J., Porter, F., Arai, H., Walkley, S. U., and D. Manor. Altered vitamin E status in Niemann-Pick type C disease. J. Lipid. Res.,2011,52,1400–1410. [PubMed]

Jeffrey Atkinson, Alexandr A. Kapralov, Naveena Yanamala, Linda Pierce, James Peterson, Yulia Y. Tyurina, Michael Epperly, Zhentai Huang, Jianfei Jiang, Akihiro Maeda, Weihong Feng, Karla Wasserlos, Natalia A. Belikova, Vladimir A. Tyurin, Jackie Fletcher, Yongsheng Wang, Judith Klein-Seetharaman, Detcho A. Stoyanovsky, Hülya Bayîr, Bruce R. Pitt, Joel S. Greenberger, Valerian E. Kagan. A mitochondria-targeted inhibitor of cytochrome c peroxidase mitigates radiation-induced death. Nature Communications 2, 2011, Article number: 497 (doi:10.1038/ncomms1499). [PubMed]

Nishio, K., Ishida, N., Saito, Y., Ogawa-Akazawa, Y., Shichiri, M., Yoshida, Y., Hagihara, Y., Noguchi, N., Chirico, J., Atkinson, J., and Etsuo Niki. α-Tocopheryl phosphate: uptake, hydrolysis, and antioxidant action in cultured cells and mouse Free Radical Biology and Medicine, 2011, 50(12), 1794–1800. [PubMed]

2010

Wen Xiao Zhang, Varsha Thakur, Andrei Lomize, Irina Pogozheva, Candace Panagabko, Matt Cecchini, Matilda Baptist, Samantha Morley, Danny Manor and Jeffrey Atkinson. The Contribution of Surface Residues to Membrane Binding and Ligand Transfer by the α-Tocopherol Transfer Protein (α-TTP). J. Mol. Biol. 2010, 405, 972-988. [PubMed]

Samantha Morley, Varsha Thakur, David Danielpour, Robert Parker, Hiroyuki Arai, Jeffrey Atkinson, Jill Barnholtz-Sloan, Eric Klein, and Danny Manor. The tocopherol transfer protein sensitizes prostate cancer cells to vitamin E. J. Biol. Chem. 2010, 285(46), 35578-35589. [PubMed]

Ryan West, Candace Panagabko, and Jeffrey Atkinson. Synthesis and Characterization of BODIPY-α-Tocopherol: A Fluorescent Form of Vitamin E. J. Org. Chem. 2010, 75(9), 2883–2892. [PubMed]

Yongsheng Wang, Candace Panagabko, Jeffrey Atkinson. Synthesis of α-tocohexaenol (α-T6) a fluorescent, oxidatively sensitive polyene analogue of α-tocopherol. Bioorganic & Medicinal Chemistry.2010 18, 777–786. [PubMed]

(Invited Review) Jeffrey Atkinson, Thad Harroun, Stephen R. Wassall, William Stillwell and John Katsaras. The location and behavior of α-tocopherol in membranes. Mol. Nutr. Food Res. 2010, 54, 1–11. [PubMed]

2009

Wen Xiao Zhang, Grant Frahm, Samantha Morley, Danny Manor and Jeffrey Atkinson. Effect of Bilayer Phospholipid Composition and Curvature on Ligand Transfer by the α-Tocopherol Transfer Protein.  Lipids 2009 (in press) [PubMed]

1. E. Kagan, A. Bayir, H. Bayir, D. Stoyanovsky, G. G. Borisenko, Y. Y. Tyurina, P. Wipf, J. Atkinson, J. S. Greenberger, R. S. Chapkin and N. A. Belikova.  Mitochondria-targeted disruptors and inhibitors of cytochrome c peroxidase complexes: A new strategy in anti-apoptotic drug discovery. Molecular Nutrition and Food Research.  2009, 104-114 [PubMed]

2008

Stephan Ohnmacht, Phillip Nava, Ryan West, Robert Parker and Jeffrey Atkinson.  Inhibition of oxidative metabolism of tocopherols with ω−N-heterocyclic derivatives of vitamin E.  Bioorganic & Medicinal Chemistry, 2008, 16(16), 7631-7638. [PubMed]

Samantha Morley, Matt Cecchini, Wendy Zhang, Alessandro Virgulti, Noa Noy, Jeffrey Atkinson, and Danny Manor.  Mechanisms of ligand transfer by the hepatic Tocopherol Transfer Protein.  J Biol Chem 2008 283(26): 17797–17804 [PubMed]

Jan Frank, Sangeun Lee, Scott W. Leonard, Jeffrey K. Atkinson,  Afaf Kamal-Eldin, and Maret G. Traber. Gender differences in the inhibition of γ-tocopherol metabolism by a single dose of dietary sesame oil in healthy subjects.  Am. J. Clin. Nutr. 2008, 87(6):1723-9 [PubMed]

Matthew A. Churchward, Tatiana Rogasevskaia, David M. Brandman, Houman Khosravani,
Phillip Nava, Jeffrey K. Atkinson, and Jens R. Coorssen.  Specific lipids supply critical negative spontaneous curvature ― an essential component of native Ca2+-triggered membrane fusion.  Biophys. J. 2008, 94(10):3976-86 [PubMed]

Jeffrey Atkinson, Raquel F. Epand, Richard M. Epand.  Tocopherols and Tocotrienols in Membranes: A Critical Review.  Free. Rad. Biol. Med. 2008 44, 739-764. [PubMed]

Stephan Ohnmacht1, Ryan West, Razvan Simionescu, Jeffrey Atkinson. Assignment of the 1H- and 13C-NMR of Tocotrienols.  Mag. Res. Chem. 2008  46(3), 287-294. [PubMed]

2007

Tae-gyu Nam, Christopher L. Rector, Hye-young Kim, Andreas F.-P. Sonnen, Roland Meyer, Werner M. Nau, Jeffrey Atkinson, Julia Rintoul, Derek A. Pratt, and Ned A. Porter.  Tetrahydro-1,8-naphthyridinol Analogues of -Tocopherol as Antioxidants in Lipid Membranes and Low-Density Lipoproteins. J. Am. Chem. Soc. 2007, 129(33), 10211 – 10219 [PubMed]

Maret G. Traber and Jeffrey Atkinson.  Vitamin E, anrtioxidant and nothing more.  Free Rad Biol Med 2007 43, 4-15. (Invited Review) [PubMed]

2006

Qian J, Atkinson J, Manor D.  Biochemical consequences of heritable mutations in the alpha-tocopherol transfer protein. Biochemistry. 2006 45(27):8236-42. [PubMed]

Nava P, Cecchini M, Chirico S, Gordon H, Morley S, Manor D, Atkinson J.
Preparation of fluorescent tocopherols for use in protein binding and localization with the alpha-tocopherol transfer protein. Bioorg Med Chem. 2006, 14(11):3721-36. [PubMed]

Jun Li, Martin C. Henmana, Jeffrey Atkinson, Solomon Fixon-Owoo, Turgut Tatlisumak, Graham G. Shaw, Karen M. Doyle, The pre-ischaemic neuroprotective effects of the polyamine analogues BU43b and BU36b in permanent and transient focal cerebral ischaemia models in mice.  2006, Brain Research, 1076(1), 209-215.

Richard S. Bruno, Scott W. Leonard, Jeffery Atkinson, Thomas J. Montine, Rajasekhar Ramakrishnan, Tammy M. Bray, Maret G. Traber.  Faster plasma Vitamin E disappearance in smokers is normalized by vitamin C supplementation.   2006 Free Radical Biology & Medicine 40, 689 – 697. [PubMed]

Samantha Morley, Valerie Curtis, Matt Cecchini, Phil Nava, Jeffrey Atkinson, and Danny Manor. Utility of a fluorescent Vitamin E analog as a probe for tocopherol transfer protein activity.  Biochemistry 2006   45(4), 1075-1081. [PubMed]

2005

Scott W. Leonard, Elaine Paterson, Jeffrey Atkinson, Rajasekhar Ramakrishnan, Carroll E. Cross, & Maret G. Traber. Studies in humans using deuterium-labeled alpha– and gamma–tocopherols demonstrate faster plasma gamma–tocopherol disappearance and greater metabolite production.  Free Radic Biol Med. 2005 38(7):857-66. [PubMed]

Qian J, Morley S, Wilson K, Nava P, Atkinson J, Manor D.  Intracellular trafficking of vitamin E in hepatocytes: the role of tocopherol transfer protein.  Lipid Res. 2005, 46(10):2072-82. [PubMed]

2004

Morley S, Panagabko C, Stocker A, Atkinson J, Manor D. Structure-function relationship in the tocopherol transfer protein. Ann N Y Acad Sci. 2004 1031:332-3.

Qian J, Wilson K, Nava P, Morley S, Atkinson J, Manor D. Intracellular Localization of {alpha}-Tocopherol Transfer Protein and alpha-Tocopherol. Ann N Y Acad Sci. 2004 1031:330-1.

Atkinson JK, Nava P, Frahm G, Curtis V, Manor D. Fluorescent Tocopherols as Probes of Inter-Vesicular Transfer Catalyzed by the alpha-Tocopherol Transfer Protein. Ann N Y Acad Sci. 2004 1031:324-7.

Lawson KA, Anderson K, Simmons-Menchaca M, Atkinson J, Sun L, Sanders BG, Kline K.
Comparison of vitamin E derivatives alpha-TEA and VES in reduction of mouse mammary tumor burden and metastasis. Exp Biol Med. 2004, 229(9), 954-63. [PubMed]

Samantha Morley, Candance Panagabko, Diana Shineman, Achim Stocker, Jeffrey Atkinson and Danny Manor.  Molecular Determinants of Heritable Vitamin E Deficiency. Biochemistry 2004, 43, 4143-4149. [PubMed]

Ming-Chieh Shun, Weiping Yu, Jeffrey Atkinson, Abdul Gapor, Bob G. Sanders, and Kimberly Kline Pro-apoptotic Mechanisms of Action of a Novel Vitamin E Analog (alpha-TEA) and a Naturally Occurring Form of Vitamin E (delta-Tocotrienol) in MDA-MB-435 Human Breast Cancer Cells. Nutrition and Cancer 2004, 48(1), 95-105

Lawson KA, Anderson K, Snyder RM, Simmons-Menchaca M, Atkinson J, Sun LZ, Bandyopadhyay A, Knight V, Gilbert BE, Sanders BG, Kline K.  Novel vitamin E analogue and 9-nitro-camptothecin administered as liposome aerosols decrease syngeneic mouse mammary tumor burden and inhibit metastasis.  Cancer Chemother Pharmacol. 2004 54(5):421-31 [PubMed]

Scott W. Leonard, Richard S Bruno, Elaine Paterson, Bettina Schock, Jeffrey Atkinson, Tammy M. Bray, Carroll E Cross, and Maret G. Traber. 5-Nitro-gamma-tocopherol increases in human plasma exposed to cigarette smoke in-vitro and in-vivo. Free Radicals in Biology and Medicine 2003, 35(12):1560-7.  [PubMed]

2003

Galli F, Lee R, Atkinson J, Floridi A, Kelly FJ. Gamma-Tocopherol biokinetics and transformation in humans. Free Radic Res. 2003, 37(11):1225-33. [PubMed]

Bradford A, Atkinson J, Fuller N, Rand RP. The effect of vitamin E on the structure of membrane lipid assemblies. J Lipid Res. 2003, 44(10):1940-5. [PubMed]

Lawson KA, Anderson K, Menchaca M, Atkinson J, Sun LZ, Knight V, Gilbert B, Conti C, Sanders BS, Kline K. Novel Vitamin E Analog Inhibits Syngeneic Mouse Mammary Tumor Growth and Blocks Lung Metastasis. Molecular Cancer Therapeutics. 2003 Molecular Cancer Therapeutics. 2003, 2, 437-444. [PubMed]

Candace Panagabko, Samantha Morley, Marta Hernandez, Patrick Cassolato, Heather Gordon, Rachel Parsons, Danny Manor and Jeffrey Atkinson.   Ligand specificity in the CRAL-TRIO protein family. Biochemistry  2003, 42(21), 6467-6474 [PubMed]

Solomon Fixon-Owoo,  Frédéric Levasseur,  Keith Williams, Thomas N. Sabado, Mike Lowe, Markus Klose, A. Joffre Mercier, Paul Fields, Jeffrey Atkinson.  Preparation and Biological Assessment of Hydroxycinnamic Acid Amides of Polyamines In press: Phytochemistry 2003, 63(3):315-34.

2002

Panagabko, C., Neely, S., Lei, H., Morley, S., Manor, D., and Atkinson, J. Expression and refolding of recombinant human alpha-tocopherol transfer protein (alpha-TTP) capable of specific alpha-tocopherol binding.  Protein Expression and Purification. 2002 , 24, 395-403

Klose, M.K., Atkinson, J.K., and Mercier, A.J.  Effects of a hydroxycinnamoyl conjugate of spermidine on arthropod neuromuscular junctions. J Comp Physiol A, 187:945-952, 2002

1991-2001

Galli, F., Lee, R., Dunster, C., Atkinson, J.K., Floridi, A.,  and Kelly, F.J.  Gamma-tocopherol metabolism and its relationship with alpha-tocopherol in humans: a stable isotope supplementation study. Biofactors 2001 15(2-4), 65-69

Lei, Huangshu; Jeffrey Atkinson. Hydrogen-deuterium scrambling during the reductive deuteration of alpha- and gamma-tocopherol chromenes Journal of Labeled Compounds and Radiopharmaceutical. 2001, 44, 215-223.

Lei, Huangshu,; Atkinson, J.K. Synthesis of phytyl and chroman derivatized photoaffinity labels based on a-tocopherol. Journal of Organic Chemistry.2000, 65(8); 2560-2567.

Panagabko, C.; Chenier, D.; Fixon-Owoo, S.; Atkinson, J.K. Ion-pair HPLC determination of hydroxycinnamic acid monoconjugates of putrescine, spermidine and spermine. Phytochemical Analysis ,2000, 11, 11-17.

Lei, H.; Marks, V.; Pasquale, T.; Atkinson, J.K. Synthesis of photoaffinity label analogues of a-tocopherol. Bioorg. Med. Chem. Letters, 1998 8, 3453-3458.

Mercier, A. Joffre; Farragher, Suzanne; Schmor, B.; Kamau, M.; Atkinson, J. Effect of a plant derived spider-toxin analogue on the crayfish neuromuscular junctions. Canadian Journal of Zoology, 1998, 76, 2103-2107.

Tays, K.; Atkinson, J.K. An improved synthesis of cyclic hydroxamic acids from Gramineae. Synthetic Communications, 1998 28(5), 903-912.

Sen, A.; Bergvinson, D.; Miller, S; Atkinson,J.K.; Fulcher, G.; Arnanson, J.T. Distribution and microchemical detection of phenolic acids, flavanoids and phenolic acid amides in maize kernels. J. Chem. Ecol. 1994 42, 1879-1883

Palli, S. R.; Touhara, K; Charles, J.-P.; Bonning, B.C.; Atkinson, J.K.; Trowell, S. C.; Hiruma, K.; Goodman, W.G.; Kyriakides, T; Prestwich, G.D.; Hammock, B. D. and Riddiford, L.M. A nuclear juvenile hormone binding protein from larvae of Manduca sexta: A putative receptor for the metamorphic action of juvenile hormone. Proceedings of the National Academy of Science USA, 1994, 91, 6191-6195.

J.K. Atkinson, J. Arnason, F. Campos, H.M. Niemeyer, H.R. Bravo, “Synthesis and Reactivity of Cyclic Hydroxamic Acids: Resistance Factors in the Gramineae”, Chapter 32 in Synthesis and Chemistry of Agrochemicals, Vol. III, ed. by D.R. Baker, J.G. Fenyes and J.J. Steffens, ACS Symposium Series, 504, 349-360 ( 1992 ).

1. Atkinson, P. Morand, J.T Arnason, H.M. Niemeyer, H. Bravo, “Synthesis of Analogues of the Cyclic Hydroxamic Acid 2,4-Dihydroxy- 7-Methoxy-1,4-Benzoxazin-3-One (DIMBOA): Their pH Dependent Decomposition and Reaction with Mercaptoethanol”, J. Org. Chem., 56, 1788-1800 ( 1991 ).

• BTEC 3P09: Bioreactor Processes
• BTEC 3P93: Proteins and Nucleic Acids
• CHEM/BTEC 4P27: Enzyme and Co-enzyme Mechanisms
• CHEM/BTEC 5P25: Medicinal Chemistry

 

The current research group:

Dr. Candace Panagabko – (Research Associate, PhD 2004)
Cloning, expression, and purification of lipid kinases from yeast (Pik1) and humans (PI(4)K); fluorescence kinase assays;  fluorescence-based ligand transfer assays and immobilized phospholipid membrane binding by phospholipid transfer proteins

 

Dr. Ahmadreza Massah – (Visiting Chemistry Scholar, PhD 1998, Professor in Organic Chemistry, Department of Chemistry, Islamic Azad University, Shahreza, Isfahan, Iran

Synthesis of non-antioxidant analogues of tocopherol, imidazole-substituted fatty acid conjugates as inhibitors of cytochrome c peroxidase, synthesis of bolaphospholipids

PhD

Tayo Laleye 

(In Progress) Thesis/Project Title: Synthesis of bola-phosphatidyl inositols and their analogues

MSc

Natalie Boccalon

(In Progress) Thesis/Project Title: Synthesis of a fluorescent form of the non-antioxidant active tocopherol analogue 6-hydroxymethyl-tocopherol

Jennifer Kujani

(In Progress) Thesis/Project Title: Phospholipid bilayer binding and lipid transfer of the α-tocopherol transfer protein explored using surface plasmon resonance.

 

Hons BSc

 

Morgan Robinson

(In Progress) Thesis/Project Title: Expression and assay of frequenin and NCS1, two myristoylated membrane binding partners for PI4K-IIIbeta.

 

Thomas Scheinkerman

(In Progress) Thesis/Project Title: Expression of human electrophile and redox sensor  Keap1 and it reaction with γ-tocopherol quinone.

 

Past Students

 

Post-Docs

Dr. Rachel Parsons, 2001-2

Dr. Frederic Levasseur, 1998

 

PhD

Mikel Ghelfi (PhD, Chemistry, 2019)
Thesis/Project Title: Synthesis of fluorescent BODIPY tocopherols and PET analogues of tocopherols
Present Position: Post-doctoral Fellow, University of Pennsylvania

Parthajit Mukherjee (PhD, Biotechnology, 2016)

Thesis/Project Title: Membrane interactions of the human oxysterol binding protein

Present Position: Senior Laboratory Demonstrator, Brock University

Matilda Baptist (PhD, Biotechnology, 2015)

Thesis/Project Title: The ligand and membrane-binding behaviour of the phosphatidylinositol transfer proteins (PITP-alpha & PITP-beta)
Present Position: Medical Science Writer / Editor

Wendy Zhang (PhD, Biotechnology. 2009)

Thesis/Project Title: Mechanism of Tocopherol Transfer by human a-Tocopherol Transfer Protein (a-hTTP)

Candace Panagabko (PhD, Biotechnology, 2004)

Ligand Specificity in the CRAL-TRIO Protein Family

 

MSc

Marcelo Muniz Correa (2023)

Thesis/Project Title: The optimization of a time-resolved, vesicle-based fluorescence assay for the activity of the lipid kinase PI4k-IIIbeta and the effect of lipid transfer proteins on enzyme activity

Present Position: PhD candidate, Université de Montreal

Sean Wilson (2023)

Thesis/Project Title: Synthesis of photocleavable bolalipids.

Present Position: Environmental Chemical Analyst, Environment and Climate Change Canada, Burlington, ON.

Vansh Mehta (2022)

Thesis/Project Title: Effect of plasma membrane and late endosomal lipids phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2 and bis-monoacylphophosphate (BMP) on the vesicle binding properties of wild-type and mutant forms of the human tocopherol transfer protein.

Yasaman Hosseini (2020)
Thesis/Project Title: Synthesis of redox sensitive and “click”-able bola- phosphatidylinositols.

Shannon Jewell (2019)

Thesis/Project Title: Synthesis of Bola-Phosphatidylinositols as Substrates for the PI-kinase Pik1
Present Position: Graduate student, University of Queensland, Australia

Kailey Meehan (2019)
Thesis/Project Title: Expression, purification, and fluorescence assay development for the yeast PI3-kinase, Pik1, and exploration of its natural and bolalipid substrate recognition efficiency supported by the yeast PITP, Sec14.

Present Position: University Chaplin, Brock University

Nicholas Krueger (2017)
Thesis/Project Title: Reactivity of tocopherol and tocotrienol derived quinones with small molecule and protein thiols and their ability to stimulate the Keap1/Nrf2 system.
Present Position: Staff Chemist, Cytec-Solvay Group

Andrew Hildering – 2016 (Chemistry)

Hasam Madarati – 2015 (Biotechnology)

Venkata Krishna Garapati Rao  – (Chemistry)

Ryan West – 2009 (Chemistry)

Matilda Baptist – 2009 (Biotechnology)

Yongsheng Wang – 2008 (Chemistry)

Grant Frahm – 2007 (Biotechnology)

Stephan Ohnmacht – 2007 (Chemistry)

Phil Nava – 2006 (Biotechnology))

Fan Gu – 2006 (Chemistry)

Marta Hernandez – 2003 (Biotechnology)

Solomon Fixon-Owoo – 2000 (Chemistry)

John Huangshu Lei – 1999 (Chemistry)

Kevin Tays – MSc 1998, Honours Thesis 1996

Graduated Hons BSc Students

Jennifer Kujani (2024)

Thesis/Project Title: A mutagenic study of the α-tocopherol transfer protein

 

Nicolas Sardella (2021)

Thesis/Project Title: Expression, isolation, and fluorescence enzyme assay development of the human phosphatidylinositol 4-kinase.

 

Marcelo Muniz Correa (2021)

Thesis/Project Title: Expression, purification, and fluorescence enzyme assay development of the human phosphatidylinositol-4-kinase: Probing the mechanism of PI- transfer proteins.

 

Yvonne Yong (2020)

Thesis/Project Title: Assessment of the binding of the mutant tocopherol transfer protein (TTP K217A) to endosomal phospholipids using surface plasmon resonance.
Present Position: Pharmacy

Cassie Bergwerff (2020)
Thesis/Project Title: Assessment of the binding of the wild-type tocopherol transfer protein (TTP) to endosomal phospholipids using surface plasmon resonance.
Present Position: Researcher, Ontario Institute for Cancer Research MaRS Centre

Sean Wilson (2020)

Thesis/Project Title: Synthesis of photocleavable bolalipids.

Present Position: Graduate Student, Brock University

Shraddha Khirwadkir (2020)
Thesis/Project Title: Expression, purification, and assay of the yeast PI-4-kinase Pik1 Present

Present Position: Graduate Student, Biochemistry, University of Toronto

Laura Voigt  (2020)
Thesis/Project Title: Synthesis of conformationally restricted biphenyl analogues of bola- phosphatidylinositols
Present Position: PhD Student, Chemistry, Brock University

Sarah Bagnarol  (2020)
Thesis/Project Title: Newly Discovered Ligand Binding Properties of the Human SEC14L4 Protein
Present Position: Teacher’s College, York University

Vansh Mehta (2019)
Thesis/Project Title: Binding of triphenylphosphonium derivatives of Vitamin E to the tocopherol transfer protein and the antioxidant activity of 6-hydroxymethyl-alpha- tocopherol.
Present Position: Graduate student, Brock University

Alessandro Perri (2017)
Thesis/Project Title: A study of Human ⍺-Tocopherol Transfer Protein’s Membrane Binding Ability on Differing Phospholipid Membranes by Surface Plasmon Resonance Present Position: Graduate student, Schulich School of Business, York University

Sam Jagas (2018)
Thesis/Project Title: Synthesis of photocleavable long chain diacids for bolalipids Present Position: National wrestling team; Teacher’s college

Jordan Willbanks
Thesis/Project Title: Characterization of a fluorescent redox-sensitive analogue of alpha- tocopherol as a probe of lipid peroxidation.
Present Position: Dentistry

Bridgette Hartley (2018)
Thesis/Project Title: Synthesis of bola-phospholipid bioconjugating probes for the lipid kinase Pik1
Present Position: Graduate student, University of Alberta

Aaron DeJong (2017)

Thesis/Project Title: Synthesis of chiral bola-glycerophospholipid analogues of phosphatidylinositol as probes of lipid kinase activity
Present Position: MBA

Loreen Bahour (2017)
Thesis/Project Title: Determination of the membrane binding affinity of mutant forms of the tocopherol transfer protein using surface plasmon resonance.
Present Position: Business and Management, Karger Publishers

Trisha Anne Thomas (2017)
Thesis/Project Title: The efficiency of phospholipid ligand pick-up by the yeast lipid transfer protein Sec14.
Present Position: Forensic Science Specialist

Kailey Meehan – BTEC 2016

Essa Alqahtani – BTEC 2016

Luke Taylor – BTEC 2015

Anas Madarti  – BTEC 2015

Nick Krueger – BTEC 2015

Hasam Madarti – BTEC 2013

Andrew Hildering – BIOL/CHEM 2013

Izabela Subczinska – BCHM 2012

Katy Howard – 2012

Cameron Miotto – BTEC 2012

Kaleigh Giles – BTEC 2011

Andrew Barty – CHEM 2011

Bryan Morris – BTEC 2011

Kaitlin Bynkoski – 2009

Mohammad Howard-Azzeh – BTEC 2009

Michael Flewelling – BTEC 2008

Alessandro Virgulti – BTEC 2007

Julia Rintoul – BTEC 2007

Matt Cecchini – BCHM 2007

John Chirico – BTEC 2007

Marie Dion – BTEC 2007

Ryan West – CHEM 2006

Robin Jansen – BTEC 2003

Pat Cassolato – BTEC 2002

Brad Harrison – BTEC 2001

Christina Pinelli – BTEC 2000

Steve Neely – BTEC 2000

Miranda Wellwood – BTEC 1999

Monika Dabrowski- BTEC 1999

Doug Burr– BTEC 1999

Brian Matier – BTEC 1999

Ken Lo – BTEC 1998

Candace Panagabko – BTEC 1998

Virginia Marks – BTEC 1998

Deb Chenier – BTEC 1998

Neil Shuart – BTEC 1998

Brad Schmor – BTEC 1997

Kathy Hillier – CHEM 1997

Dave Green – CHEM 1995

Steve Jenkins – CHEM 1995

 Summer Research Assistants

Nicolas Sardella – NSERC USRA, 2020

Rachel Ciccone – Match of Minds, 2020

Alessandro Fabiano – NSERC USRA, 2019

Marcelo Muniz Correa – Match of Minds, 2018

Shraddha Khirwadkar – NSERC USRA, 2019, Match of Minds, 2017

Alessandro Perri – NSERC USRA, 2017

Mateo Andrade – NSERC USRA, 2017

Aaron de Jong – 2016, NSERC USRA, 2017

Kailey Meehan – Match of Minds, 2016

Patrick Roy-Gayos – NSERC USRA, 2015

Uzair Sayani – 2015

Joanna Boucard – 2014

Hasam Madarati – NSERC USRA, 2012

Kaleigh Giles – 2008

Michael Flewelling – NSERC USRA, 2008

Marie Dion – NSERC USRA 2005

Ryan West -2005

Abdullah Mahboob – 2004

Tony Pasquale – 1996

Luke Landry – 1995

High School Mentorship Students 

Morgan Robinson (2020)

Greater Fort Eerie Secondary School

Thesis/Project Title: Can the tocopherol transfer protein be stored frozen without denaturation or precipitation?
Present Position: High school student, Greater Fort Eerie Secondary School

Curtis Ehlert (2018)

Governor Simco High School
Thesis/Project Title: Synthesis of very long chain dicarboxylic acids for membrane- spanning bolaphospholipids
Present Position: Schulich School of Business

Kirztyn de Torres (2018)

Holy Cross Catholic Secondary School

Thesis/Project Title: Ligand binding ability of TTPL1 and Sec14L4 proteins Present Position: Undergraduate student, Brock University

Dylan Perera (2015)

A.N. Myer Secondary School
Thesis/Project Title: Synthesis of Bola-Lipids: Hunting for Lipid-Binding Proteins

Present Position: Undergraduate, Biochemistry (Univ. of Waterloo)

Holly Phillbrick (2015)

Laura Secord Secondary School
Thesis/Project Title: Synthesis and assessment of a vitamin E analogues lacking all antioxidant activity: 6-hydroxymethyl-alpha-tocochroman
Graduated from McMaster University

Tristyn Clarke (2014)

Samford Collegiate
Thesis/Project Title: Synthesis of naphthol and phenol-based inhibitors of monooxygenases involved in tocopherol and tocotrienol metabolism
Graduated Biomedical Sciences, Brock University

Rebecca Bunz – 2007

Dennis Moore  – 1999

Ben Lichty – 1998

 

Research Assistants

Tammy Keifer – 1999

Muthoni Kamau – 1996