Michael Lucido.

Michael Lucido

Department

Structural Biology

Thesis

PhD Thesis title: The inhibition of cyclooxygenases by nonspecific nonsteroidal anti-inflammatory drugs: Probing the differential effect of aspirin on COX-2

Date of Completion of PhD: June 22, 2015

Residency

Psychiatry/Research, Emory University

Undergraduate Education

Psychology and Pre-Medical Chemistry,
Florida Institute of Technology

Thesis Advisor

Utilizing in vitro methods, I am assessing the observed differential effect of classic, “nonselective” NSAIDs on cyclooxygenase (COX) isozyme activity. In short, aspirin is a covalent inhibitor of COX activity that acetylates an active site serine. In COX-1, the acetylation confers complete inhibition. In COX-2, however, there is persistent activity despite acetylation and there is a concomitant alteration in the product profile from generation of predominantly prostaglandin H2 (PGH2) to 15­R-hydroxyeicosatetraenoic acid (15R-HETE). 15R-HETE is a precursor in the production of 15-epi-lipoxins in vivo, which are pro-resolving lipid mediators. The alteration in regio- and stereoselectivity induced by acetylation of COX-2 is a matter of debate and the molecular basis is yet to be elucidated. Using recombinant technologies, functional assays, chromatographic techniques, and x-ray crystallography, I hope to shed light onto the matter.

Publications

  • Orlando, B.J., McDougle, D.R., Lucido, M.J., Eng, E. T., Graham, L.A, Schneider, C., Stokes, D.L., Das, A., and Malkowski, M.G. (2014) Cyclooxygenase-2 Catalysis and Inhibition in Lipid Bilayer Nanodiscs. Arch. Biochem. Biophys., 546, 33-40.
  • Orlando, B.J., Lucido, M.J., and Malkowski, M.G. (2015) The structure of ibuprofen bound to cyclooxygenase-2. J. Struct. Biol., 189, 62-66.
  • Lucido, M.J., Orlando, B.J., Schneider, C., and Malkowski, M.G. (2016) Crystal Structure of Aspirin-Acetylated Human Cyclooxygenase-2: Insight into the Formation of Products with Reversed Stereochemistry. Biochemistry, 55(8), 1226-1238.

Professional/Educational Meetings/Abstracts

  • Lucido, M.J., Orlando, B.J., and Malkowski, M.G. Role of Phe-205 in Determining the Stereoselectivity of Arachidonate Oxygenation by Aspirin-Acetylated Cyclooxygenase-2. Pittsburgh Diffraction Conference, Buffalo, September 2013.
  • Orlando, B.J., McDougle, D., Lucido, M.J., Eng, E., Stokes, D., Das, A., and Malkowski, M.G. Lipid Bilayer Nanodisc Incorporation Facilitates the Investigation of Membrane Bound COX-2. Pittsburgh Diffraction Conference, Buffalo, September 2013.
  • Lucido, M.J., Orlando, B.J., and Malkowski, M.G. The Generation of 15R-HETE by Aspirin-acetylated Cyclooxygenase-2: The Role of Phe-205. Bioactive Lipids in Cancer, Inflammation, and Related Diseases 13th International Conference, Puerto Rico, November 2013.
  • Orlando, B.J., McDougle, D., Lucido, M.J., Eng, E.T., Stokes, D.L., Das, A., and Malkowski, M.G. Lipid Bilayer Nanodiscs as a Tool in the Study of Membrane-Associated Cyclooxygenase-2. Bioactive Lipids in Cancer, Inflammation, and Related Diseases 13th International Conference, Puerto Rico, November 2013.
  • Orlando, B.J., McDougle, D., Lucido, M.J., Eng, E.T., Graham, L.A., Schneider, C., Stokes, D.L., Das, A., and Malkowski, M.G. Investigating Cyclooxygenase-2 Function in Detergent-Free Nanoscale Lipid Bilayer Discs. 15th International Winter Eicosanoid Conference, Baltimore, March 2014.
  • Lucido, M.J., Orlando, B.J., and Malkowski, M.G. Stereoselectivity of Arachidonate Oxygenation: The Role of Phe-205 in Aspirin Acetylated Cyclooxygenase-2. 15th International Winter Eicosanoid Conference, Baltimore, March 2014.
  • Lucido, M.J., Orlando, B.J., and Malkowski, M.G. Insights into Aspirin-Mediated Acetylation of Cyclooxygenase-2: Implications of the Solubilization System on in vitro Inhibition. 2014 MSTP Tri-Institutional Research Conference, Rochester, October 2014.
  • Orlando, B.J., McDougle, D., Lucido, M.J., Eng, E.T., Graham, L.A., Schneider, C., Stokes, D.L., Das, A., and Malkowski, M.G. Catalysis and Inhibition of a Monotopic Membrane Enzyme in Lipid Bilayer. Membrane Protein Structures 2015 Meeting, Chicago, April 2015.

Medical School Activities

  • Anesthesiology Interest Group – President, 2011-2012
  • Student AMA – Member, 2010-2012

Extracurricular Interests

Baseball, beer and wine tasting