Overview

Our lab engineers innovative protein-polymer tools and drug carriers that respond to their environment. Cancer and ocular drug delivery are our primary focus; however, we also develop biomaterials that modulate cell signaling and trafficking. Protein-polymers are repetitive polypeptides that can be expressed in cells, fused to functional peptides, and tuned to respond to cues such as temperature, concentration, or nanoassembly. Composed from genetically-engineered biomaterials, their sequence and behavior can be precisely tailored at the genetic level. Drug delivery in the eye and cancer is often limited by access to and retention at the target site. In addition, many small molecules are dose-limited by toxicity at peripheral sites in the body. Our strategy is to repackage drugs and functional peptides into protein-polymers that control release and reduce toxicity. Successful carrier strategies are being formulated and evaluated for translation to the clinic. Using these biomaterials, our group has recently made significant breakthroughs by assembling ‘microdomains’ inside living cells. When decorated with functional proteins, these microdomains are helping us to precisely modulate cellular biology. To explore the potential for these new tools, we explore fundamental relationships between microdomain phase behavior and interactions with other proteins, membranes, organelles, and cells. Please explore our lab website to learn more about our work.

Dr. MacKay received his SB in chemical engineering and biology from the Massachusetts Institute of Technology in 1999. A Howard Hughes Medical Institute Predoctoral Fellow, he completed his PhD at the University of California at San Francisco and Berkeley in the joint graduate group in Bioengineering in 2005. As a Kirschstein National Research Service Award Postdoctoral Fellow, Dr. MacKay studied at Duke University in the Department of Biomedical Engineering. In 2008 Dr. MacKay joined the faculty at the University of Southern California. Dr. MacKay is a full member of the USC Norris Comprehensive Cancer Center. He has authored over 49 peer-reviewed publications. His work is and has been supported by the US Army, NIH/NIGMS, NIH/NIBIB, NIH/NEI, StopCancer, USC Ming Hsieh Institute, and the USC Whittier Foundation. His group explores biomolecular engineering and nanomedicine. At the USC School of Pharmacy, Dr. MacKay has deep expertise teaching drug delivery, nanoscience, and pharmacokinetics.

Research Funding

  • Protein-polymer nanomedicine for Sjogren's Syndrome
    NIH · R01EY026635 · Mar 1, 2017 – Dec 31, 2027 · Role: Co-Principal Investigator
  • Intracellular switching using genetically engineered protein microdomains
    NIH · R01GM114839 · Apr 1, 2015 – Mar 31, 2021 · Role: Principal Investigator
  • A rapid, reversible switch for controlling intracellular trafficking
    NIH · R21EB012281 · Jul 1, 2010 – Jun 30, 2013 · Role: Principal Investigator
  • pH sensitive elastin-like-peptides for tumor targeting
    NIH · F32CA123889 · Jul 1, 2006 – Jun 30, 2008 · Role: Principal Investigator

Publications

  • Anti-FLT3 nanoparticles for acute myeloid leukemia: Preclinical pharmacology and pharmacokinetics. J Control Release. 2020 08 10; 324:317-329.. View in PubMed
  • Human Granulocyte-Macrophage Colony-Stimulating Factor Fused to Elastin-Like Polypeptides Assembles Biologically-Active Nanoparticles. Bioconjug Chem. 2020 05 20; 31(5):1551-1561.. View in PubMed
  • A Multivalent ICAM-1 Binding Nanoparticle which Inhibits ICAM-1 and LFA-1 Interaction Represents a New Tool for the Investigation of Autoimmune-Mediated Dry Eye. Int J Mol Sci. 2020 Apr 15; 21(8).. View in PubMed
  • Evaluation of extracellular matrix mimetic laminin bioactive peptide and elastin-like polypeptide. FASEB J. 2020 05; 34(5):6729-6740.. View in PubMed
  • Nanotoxicology of an Elastin-like Polypeptide Rapamycin Formulation for Breast Cancer. Biomacromolecules. 2020 03 09; 21(3):1091-1102.. View in PubMed
  • Advanced drug delivery 2020 – Parts 1,2 and 3. Adv Drug Deliv Rev. 2020; 156:1-2.. View in PubMed
  • Caveolin elastin-like polypeptide fusions mediate temperature-dependent assembly of caveolar microdomains. ACS Biomater Sci Eng. 2020 01 13; 6(1):198-204.. View in PubMed
  • The humanin peptide mediates ELP nanoassembly and protects human retinal pigment epithelial cells from oxidative stress. Nanomedicine. 2020 02; 24:102111.. View in PubMed
  • Molecular Targeting of Immunosuppressants Using a Bifunctional Elastin-Like Polypeptide. Bioconjug Chem. 2019 09 18; 30(9):2358-2372.. View in PubMed
  • Generation of a Monoclonal Antibody to Detect Elastin-like Polypeptides. Biomacromolecules. 2019 08 12; 20(8):2942-2952.. View in PubMed