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Carlos Enrique Catalano, PharmD, PhD

Professor, Department of Pharmaceutical Sciences


Mailing Address

University of Colorado
Skaggs School of Pharmacy and Pharmaceutical Sciences
Mail Stop C238
12850 E. Montview Blvd. V20-4118
Aurora, CO 80045

Office Location

Pharmacy and Pharmaceutical Sciences Building (V20)
Fourth Floor
Room 4118

Lab Location

Pharmacy and Pharmaceutical Sciences Building (V20)
Fourth Floor
Room 4450A

Contact

Affiliations

  • Pharmaceutical Sciences Program

Training and Education

  • B.A., Biochemistry, 1979, San Francisco State University, San Francisco, California
  • Pharm.D., Clinical Pharmacy, 1983, University of California, San Francisco, California
  • Ph.D., Medicinal Chemistry, 1987, University of California, San Francisco, California

Teaching

Professional Program

  • PHRD5915: Modern Drug Design & Drug Action

Research Interests

The studies performed in my lab fall into three broad categories that seek to understand the molecular mechanisms of virus development in the complex double-stranded DNA (dsDNA) viruses. The first project centers on the enzymology of terminase, the DNA packaging motor of bacteriophage lambda. This motor is among the most powerful known in biology; it packages the viral genome into a preformed procapsid shell to liquid crystalline density, which ultimately generates over 25 atmospheres of internal pressure. We utilize detailed enzyme kinetic, biochemical, and biophysical approaches to dissect the intimate details of motor structure and function. The second project focuses on the procapsid into which the genome is packaged. The structure is assembled from 415 copies of the major capsid protein that forms an icosahedral shell and a dodecameric portal protein ring situated at a unique vertex of the icosahedron; the portal vertex serves as a conduit through which DNA enters during particle assembly and exits during infection. We utilize biochemical, biophysical, and structural approaches to interrogate the mechanism of procapsid assembly and to characterize the thermodynamic features of a remarkable capsid expansion transition that is triggered by DNA packaging. The third project seeks to harness the lambda capsid as nanoparticle for “theragnostic” applications (Viral Bioengineering). We have developed an in vitro assembly system that allows “decoration” of the capsid surface with proteins, peptides, and non-proteinaceous ligands including small molecules, carbohydrates, and synthetic polymers. Further, the shell interior can be loaded with nucleic acid, small molecule (drug), synthetic polymer, and/or inorganic (quantum dot) “cargo” for therapeutic and/or diagnostic applications. The particles can be specifically modified to afford “designer” nanoparticles of defined and tunable composition.

Representative Publications

  • Andrews, B.T. and Catalano, C.E. (2013) “Strong Subunit Coordination Drives a Powerful Viral DNA Packaging Motor” Proc. Natl. Acad. Sci. USA, 110, 5909-5914.
  • Sanyal, S.J., Yang, T.-C. and Catalano, C.E. (2014) “Integration Host Factor Assembly at the Cohesive End Site of the Bacteriophage Lambda Genome: Implications for Viral DNA Packaging and Bacterial Gene Regulation” Biochemistry, 53, 7459-7470.
  • Medina, E., Nakatani, E., Kruse, S. and Catalano, C.E. (2012) “Thermodynamic Characterization of Viral Procapsid Expansion into a Functional Capsid Shell” J. Mol. Biol., 418, 167–180.
  • Singh, P., Nakatani, E., Goodlett, D.R. and Catalano, C.E. (2013) “A Pseudo-Atomic Model for the Capsid Shell of Bacteriophage Lambda Using Chemical Cross-Linking/Mass Spectrometry and Molecular Modeling” J. Mol. Biol., 425, 3378-3388.
  • Chang, J.R., Song, E.-H., Nakatani-Webster, E., Monkkonen, L., Ratner, D.M. and Catalano, C.E. (2014) “Phage Lambda Capsids as Tunable Display Nanoparticles” Biomacromolecules, 15, 4410-4419.

Keywords

Virus assembly, biochemistry, biophysics, molecular motors, nanoparticles, viral bioengineering, theragnostics.

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