Chemistry and Biochemistry 918-631-2319
Robert Sheaff's lab investigates the biochemical basis of human diseases like cancer and neurodegeneration. Projects in cancer biochemistry center on how disrupted signaling contributes to aberrant cell cycle progression and altered metabolic pathways. Collaborative drug discovery and characterization projects focus on screening chemical libraries and evaluating novel chemotherapeutic agents. Work on neurodegenerative diseases investigates the role of deregulated protein degradation by the ubiquitin-proteasome system. A third area of research involves identifying biological markers of the human stress and pain responses, which is carried out in collaboration with members of the Psychology Department.
Ph.D., University of Colorado-Boulder
B.A., University of North Carolina-Chapel Hill
Cancer Cell Metabolism
Screening Natural Product Libraries for Novel Therapeutics
Deregulation of Cell Cycle in Cancer
Regulation of the Tumor suppressor p27kip1
Biochemistry of Cancer
Biochemistry of Cell Fate
Introduction to Biochemistry
The following may be selected publications rather than a comprehensive list.
Elliott, M et al. “Identification of Novel Proteasome Inhibitors from an Enaminone Library.” Chemical biology & drug design (2014): n. pag. Print.
Caruso, J.F., et al., Salivary hormonal values from high-speed resistive exercise workouts. Journal of Strength and Conditioning Research, 2012. 26(3): p. 625-632.
Bedford R, LePage D, Hoffmann R, Kennedy S, Gutschenritter T, Bull L, Sujijantarat N, DiCesare JC, Sheaff RJ. Luciferase inhibition by a novel naphthoquinone. Journal of Photochemistry and Photobiology B: Biology 107: 55–64, 2012.
Sherwood, Vaughn et al. “Altered UV Absorbance and Cytotoxicity of Chlorinated Sunscreen Agents.” Cutaneous and ocular toxicology 31.4 (2012): 273–279. Print.
Kennedy S, DiCesare JC, Sheaff RJ. Topoisomerase I/II Inhibition by a Novel Naphthoquinone Containing a Modified Anthracycline Ring System. Biochemical and Biophysical Research Communications. vol 408, Issue 1, 29 April 2011, pgs 94-98.
Palit, S.,** Sheaff, R. J., France, C. R., McGlone, S., Potter, W., Harkness, A., McNulty, J., Bartley, E. J.,* Hoffman, R., Monda, J. K., & Rhudy, J. L. (2011). Serotonin transporter gene (5-HTTLPR) polymorphisms are associated with emotional modulation of pain but not emotional modulation of spinal nociception. Biological Psychology, 86, 360-369. PMID: 21291949
Kennedy S, DiCesare JC, Sheaff RJ. Topoisomerase I inactivation by a novel thiol reactive Naphthoquinone. Biochemical and Biophysical Research Communications. 410 (2011) pgs 152–158.
Carvajal D, Kennedy S, Boustani A, Lazare M, Nguyen S, DiCesare JC, Sheaff RJ. Cell Death Induction and Topoisomerase I/II Inhibition by a Novel Naphthaquinone Containing a Modified Anthracycline Ring System. Chem Biol Drug Des., 78: 764–777, 2011.
Palit S, Sheaff RJ, France CR, McGlone S, Potter WT, Harkness A, McNulty J, Bartley EJ, Hoffmann R, Monda JK, Rhudy JL. Serotonin Transporter Gene (SLC6A4) Polymorphisms and Emotional Modulation of Pain and Nociception. Biological Psychology 86 (2011) 360–369.
Nacusi L, Sheaff RJ. Deregulation of cell cycle machinery in pancreatic cancer. Pancreatology; 7:373-377, 2007.
Nacusi L, Sheaff RJ. Akt phosphorylates p27kip1 at a noncononical but evolutionarily conserved site. Cell Division. 1:11, 2006.
Wang W, Nacusi L, Sanford E, Sheaff RJ, Lui X. Regulation of p21Cip1/WAF1 Ubiquitination by SCFSkp2: Substrate Requirement and Ubiquitination Site Selection. Biochemistry, 44: 14553-14564, 2005.
Moeller SJM, Head E, Sheaff RJ. p27Kip1 inhibition of GRB2-SOS formation can regulate Ras activation. Molecular and Cellular Biology 23: 3735–3752, 2003.
Sheaff RJ, Singer J, Swanger J, Smitherman M, Roberts JM, Clurman BE. Proteasome-dependent turnover of p21cip1 does not require p21 ubiquitination. Molecular Cell 5:403-410, 2000.
Sheaff RJ, Groudine M, Gordon M, Roberts JM, Clurman BE. Cyclin E-Cdk2 is a Regulator of P27kip1. Genes and Development 11:1464-1478, 1997.
Sheaff RJ, Roberts JM. End of the Line–Proteolytic Degradation of Cyclin Dependent Kinase Inhibitors. Chemistry and Biology 3:869-873, 1996.
Clurman BE, Sheaff RJ, Thress K, Groudine M, Roberts JM. Turnover of Cyclin E by the Ubiquitin-Proteasome Pathway is Regulated by CDK2 Binding and Cyclin Phosphorylation. Genes and Development 10:1979-1990, 1996.
Thompson HC, Sheaff RJ, Kuchta RD. Interactions of Calf Thymus DNA Polymerase with Primer/Templates. Nucleic Acids Research, 20:4109-4115, 1995.
Sheaff RJ, Roberts JM. Lessons in p16 from Phylum Falconium. Current Biology 1:28-31, 1995.
Sheaff RJ, Kuchta RD, Ilsley D. DNA Polymerase: Primase- “Communication” and Primer:Template Movement Between Two Active Sites. Biochemistry 33:2247-2254, 1994.
Sheaff RJ, Kuchta RD. Misincorporation of Nucleotides by Calf Thymus DNA Primase and Elongation of Primers Containing Multiple Non-cognate Nucleotides by DNA Polymerase alpha. Journal of Biological Chemistry 30:19225-19231, 1994.
Sheaff RJ, Kuchta RD. Mechanism of Calf Thymus DNA Primase: Slow Initiation, Rapid Polymerization and Intelligent Termination. Biochemistry 32:3027-3037, 1993.
Sheaff RJ, Ilsley D, Kuchta RD. Mechanism of DNA Polymerase alpha Inhibition by Aphidicolin. Biochemistry 30:8590-8597, 1991
Steven Kennedy, Hannah Berrett and Robert J. Sheaff (2012). Disruption of Cell Cycle Machinery in Pancreatic Cancer, Pancreatic Cancer - Molecular Mechanism and Targets, Sanjay K. Srivastava (Ed.), ISBN: 978-953-51-0410-0
Nacusi L, Sheaff RJ. Cell cycle control of stem cell fate. In “Stem Cells and Regenerative Medicine,” Low W, Verfaillie C (ed), World Scientific Publishing, 2008.
Moeller SM, Sheaff RJ. G1 Phase: Components, Conundrums, Context. Results and Problems in Cell Differentiation. Kaldis, P. (ed): Springer Verlag, Berlin, 2005.
Sheaff RJ, Roberts JM: Regulation of G1 Phase. Cell Cycle Control: Results and Problems in Cell Differentiation. Pagano M (ed): Springer Verlag, Berlin, 1997, 1-27.
Sheaff RJ, Regulation of Mammalian Cyclin-Dependent Kinase 2, in Dunphy WG (ed): Methods in Enzymology, Vol 283, Academic Press, New York, NY, 1997, p. 173-193.
Nho SR and Sheaff RJ. P27kip1 contributions to cancer. Progress in Cell Cycle Research: Cell Cycle Regulators as Therapeutic Targets, vol. 5. Meijer, L (ed). 2002.
Fitzgerald, Casey, Robert Sheaff, and Gordon Purser. “Effect of Environment on Antioxidant Properties of Lipoic Acid.” ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. Vol. 243. 2012. Print.
Sherwood, Vaughn, Robert Sheaff, and Gordon Purser. “Toxicity of Chlorinated Sunscreen Agents.” ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. Vol. 241. 2011. Print.
Palit, S.**, Hoffmann, R., Sheaff, R. J., McGlone, S., France, C. R., Potter, W., Harkness, A., McNulty, J., Bartley, E. J. *, Monda, J. K., & Rhudy, J. L.. Associations between serotonin transporter gene (SLC6A4) polymorphisms and emotional modulation of pain and nociception. Program No. 487.1/XX13. 2010 Neuroscience Meeting Planner, San Diego, CA: Society for Neuroscience, 2010. Online.
Quick, B., et al., Gene markers in post-traumatic stress disorder. Abstracts of Papers, 239th ACS National Meeting, San Francisco, CA, United States, March 21-25, 2010, 2010: p. CHED-539.
Palit, S. **, Hoffmann, R., Monda, J. K., DelVentura, J. L. *, Bartley, E. J. *, Sheaff, R. J., Potter, W., France, C. R., Harkness, A., McNulty, J., & Rhudy, J. L. (2009). Do 5-HT Transporter Gene (SLC6A4) Polymorphisms Confer Risk for Situation-Specific Pain Catastrophizing?: A Pilot Study. Program No. 779.2. Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience, 2009. Online.
Hughes, R.C., et al., Understanding genetic characteristics of the human stress response. Abstracts of Papers, 237th ACS National Meeting, Salt Lake City, UT, United States, March 22-26, 2009, 2009: p. CHED-430