The Faculty

Professor Spencer received his undergraduate education at Amherst College and his graduate education at the University of Wisconsin, from which he received his Ph.D. degree in 1960. He has taught at Dartmouth since that time, becoming New Hampshire Professor of Chemistry in 1972. He was an Alfred P. Sloan Fellow during 1965-68 and served as Department Chairman from 1969-1973. Over the years his research interests have broadened from pure in organic synthesis to include several areas of bioorganic chemistry, such as enzyme model systems and inhibitors, oxysterol regulation of cholesterol metabolism, and photoaffinity labeling analogs of cholesterol and phosolipids. He is currently a Research Professor of Chemistry.

Name : Thomas A. Spencer (e-mail)
Position: Professor of Chemistry Emeritus

Research Interests

Professor Spencer has research interests in a number of areas of organic and bioorganic chemistry. All of these projects involve organic synthesis as the principal activity; some involve, in addition, various biochemical experiments in collaboration with other laboratories. Recent emphasis has been on several aspects of steroid chemistry and biochemistry. The discovery that 24(S),25-epoxycholesterol is present in normal cells has led to extensive investigations of the roles of this and other oxysterols in regulation of cholesterol metabolism, for example as ligands for the LXR nuclear receptor. An ongoing interest in the mechanisms of action of enzymes involved in cholesterol biosynthesis, particularly squalene synthase, has led to an investigation of how biochemical carbocation intermediates can be stabilized by pi complexation with aromatic side chain amino acid residues of enzymes. This project is being pursued both computationally and experimentally in model systems (in collaboration with R. Ditchfield). A new and major area of research is the design and synthesis of photoactivable analogs of cholesterol and phospholipids for use in covalent labeling of proteins involved in cholesterol transport and HDL formation, in order to gain greater understanding of these physiologically important processes.

Selected Publications

• "Cholesterol Surrogates Incorporating a Benzophenone as Part of the Sterol Tetracycle:, Gan, Y.; Spencer, T.A. J. Org. Chem., 2006, 71, 5870-5875.
• "Nonsteroidal Benzophenone-Containing Analogs of Cholesterol", Gan, Y.; Blank, D.H.; Ney, J.E.; Spencer, T.A. J. Org. Chem., 2006, 71, 5864-5669.
• "Preparation and Biochemical Evaluation of Fluorenone-Containing Lipid Analogs", Spencer, T.A.; Wang, P.; Popoici-Muller, J.V.; Peltan, I.D.; Fielding, P.E.; Fielding, C.J. Bioorg. Med. Chem. Lett., 2006, 16, 3000-3004.
• "Molecular Mechanism of Reverse Cholesterol Transport: Reaction of Pre-β-Migrating High-Density Lipoprotein with Plasma Lecithin/Cholesterol Acyltransferase", Nakamura, Y.; Kotite, L.; Gan, Y.; Spencer, T.A.; Fielding, C.J.; Fielding, P.E. Biochemistry, 2004, 434, 14811-14820.
• "Benzophenoe-Containing Cholesterol Surrogates: Synthesis and Biological Evaluation", Spencer, T.A.; Wang, P.; Li, D.; Russel, J.S.; Blank, D.H.; Fielding, P.E.; Fielding, C.J. J. Lipid Res., 2004, 45, 1510-1518.
• "Synthesis of Benzophenoe-Containing Analogues of Phosphatidylcholine", Wang, P.; Blank, D.H.; Spencer, T.A. J. Org. Chem. 2004, 69. 2693-2702.
• "Sterol Efflux to Apolipoprotein A-I Originates from Caveolin-Rich Microdomains and Protentiates PDGF-Dependent Protein Kinase Activity", Fielding, P.E.; Russel, J.S., Spencer, T.A.; Hakamata, H.; Nagao, K.; Fielding, C.J. Biochemistry 2002, 41, 4929-4937.
• "Key Regulatory Oxysterols in Liver: Analysis as Δ4-3-Ketone Derivatives by High Performance Liquid Chromatography and Response to Physiological Perturbations", Zhang, Z.; Li, D.; Blanchard, D.E.; Lear, S.R.; Erickson, S.K.; Spencer, T.A. J. Lipid Res., 2001, 42, 649-658.
• "Sterol Efflux to Apolipoprotein A-I Originates from Caveolin-Rich Microdomains and Potentiates PDGF-Dependent Protein Kinase Activity", Fielding, P.E.; Russel, J.S; Spencer, T.A; Hakamata, H.; Nagao, K.; Fielding, C.J. Biochemistry 2002, 41, 4929-4937.
• "Pharmacophore Analysis of the Nuclear Oxysterol Receptor LXRα", Spencer, T.A.; Li, D.; Russel, J.S.; Collins, J.L.; Bledsoe, R.K.; Consler, T.G.; Moore, L.B.; Galardi, C.M.; McKee, D.D.; Moore, J.T.; Watson, M.A.; Parks, D.J.; Lambert, M.H.; Willson, T.M. J. Med. Chem., 2001, 44, 886-897.
• "Synthesis of 7α-Hydroxy Derivatives of Regulatory Oxysterols", Li, D.; Spencer, T.A. Steroids 2000, 65, 529-535.
• "Further Studies on the synthesis of 24(S),25-Epoxycholesterol. A New Efficient Preparation of Desmosterol", Spencer, T.A.; Li, D.; Russel, J.S.; Tomkinson, N.C.O.; Willson, T.M. J. Org. Chem.2000, 65, 1919-1923.
• "Synthesis and Evaluation of Sulfobetaine Zwitterionic Inhibitors of Squalene Synthase", Spencer, T.A.; Onofrey, T.J.; Cann, R.O.; Russel, J.S.; Lee, L.E.; Blanchard, D.E.; Castro, A.; Gu, P.; Jiang, G.; Shechter, I. J. Org. Chem. 1999, 64, 807-818.
• "Efficient, Stereoselective Synthesis of 24(S),25-Epoxycholesterol", Tomkinson, N.C.O.; Willson, T.M.; Russel, J.S.; Spencer, T.A. J. Org. Chem. 1998, 63, 9919-9923.
• "ACAT-2, A Second Mammalian Acyl CoA:Cholesterol Acyltransferase: Its cloning, expression, and characterization", Cases, S.; Novak, S.; Zheng, Y-W.; Myers, H.M.; Lear, S.R.; Sande, E.; Welch, C.B.; Lusis, A.J.; Spencer, T.A.; Krause, B.R.; Erickson, S.K.; Farese, Jr., R.V. J. Biol. Chem. 1998, 273, 26755-26764.
• "Function-Structure Studies and Identification of Three Enzyme Domains Involved in the Catalytic Activity in Rat Hepatic Squalene Synthase", Gu, P.; Ishii, Y.; Spencer, T.A.; Shechter, I. J. Biol. Chem. 1998, 273, 12515-12525.
• "Carbocation-Pi Interaction: Computational Study of Complexation of Methyl Cation with Benzene and Comparisons with Related Systems", Miklis, P.C.; Ditchfield, R.; Spencer, T.A. J. Am. Chem. Soc. 1998, 120, 10482-10489.
• "The Singular Reductions of 1,8-bis-Hydroxymethylnaphthalene for a Benzonorcaradiene by LiAlH4", Popovici-Muller, J.V.; Spencer, T.A. Tetrahedron Lett. 1997 38, 8161-8164.
• "Activation of the Nuclear Receptor LXR by Oxysterols Defines a New Hormone Response Pathway", Lehmann, J.M.; Kliewer, S.A.; Moore, L.B.; Smith-Oliver, T.A.; Oliver, B.B.; Su, J-L.; Sundseth, S.S.; Winegar, D.A.; Blanchard, D.E.; Spencer, T.A.; Willson, .M. J. Biol. Chem. 1997, 272.