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

  • An amphipathic alpha-helical peptide from apolipoprotein A1 stabilizes protein polymer vesicles. J Control Release. 2014 Oct 10; 191:15-23.. View in PubMed
  • Multimeric disintegrin protein polymer fusions that target tumor vasculature. Biomacromolecules. 2014 Jul 14; 15(7):2347-58.. View in PubMed
  • Protein polymer nanoparticles engineered as chaperones protect against apoptosis in human retinal pigment epithelial cells. J Control Release. 2014 Oct 10; 191:4-14.. View in PubMed
  • Genetically engineered nanocarriers for drug delivery. Int J Nanomedicine. 2014; 9:1617-26.. View in PubMed
  • A hybrid protein-polymer nanoworm potentiates apoptosis better than a monoclonal antibody. ACS Nano. 2014 Mar 25; 8(3):2064-76.. View in PubMed
  • A quantitative recipe for engineering protein polymer nanoparticles. Polym Chem. 2014 Jan; 5(5):1614-1625.. View in PubMed
  • Triggered sorting and co-assembly of genetically engineered protein microdomains in the cytoplasm. Adv Mater. 2014 Jan 22; 26(3):449-54.. View in PubMed
  • A rapamycin-binding protein polymer nanoparticle shows potent therapeutic activity in suppressing autoimmune dacryoadenitis in a mouse model of Sjögren’s syndrome. J Control Release. 2013 Nov 10; 171(3):269-79.. View in PubMed
  • Elastin-based protein polymer nanoparticles carrying drug at both corona and core suppress tumor growth in vivo. J Control Release. 2013 Nov 10; 171(3):330-8.. View in PubMed
  • Switchable elastin-like polypeptides that respond to chemical inducers of dimerization. Biomacromolecules. 2013 Apr 08; 14(4):976-85.. View in PubMed