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

  • Berunda Polypeptides: Multi-Headed Fusion Proteins Promote Subcutaneous Administration of Rapamycin to Breast Cancer In Vivo. Theranostics. 2017; 7(16):3856-3872.. View in PubMed
  • Elastin-like polypeptide switches: A design strategy to detect multimeric proteins. Protein Sci. 2017 Sep; 26(9):1785-1795.. View in PubMed
  • Rapamycin Eye Drops Suppress Lacrimal Gland Inflammation In a Murine Model of Sjögren’s Syndrome. Invest Ophthalmol Vis Sci. 2017 01 01; 58(1):372-385.. View in PubMed
  • Elastin-like polypeptides: Therapeutic applications for an emerging class of nanomedicines. J Control Release. 2016 10 28; 240:93-108.. View in PubMed
  • Image-driven pharmacokinetics: nanomedicine concentration across space and time. Nanomedicine (Lond). 2015; 10(18):2861-79.. View in PubMed
  • Engineering structure and function using thermoresponsive biopolymers. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2016 Jan-Feb; 8(1):123-38.. View in PubMed
  • Tear-mediated delivery of nanoparticles through transcytosis of the lacrimal gland. J Control Release. 2015 Jun 28; 208:2-13.. View in PubMed
  • Lacritin-mediated regeneration of the corneal epithelia by protein polymer nanoparticles. J Mater Chem B. 2014 Dec 14; 2(46):8131-8141.. View in PubMed
  • A thermo-responsive protein treatment for dry eyes. J Control Release. 2015 Feb 10; 199:156-67.. View in PubMed
  • Flipping the Switch on Clathrin-Mediated Endocytosis using Thermally Responsive Protein Microdomains. Adv Funct Mater. 2014 Sep 10; 24(34):5340-5347.. View in PubMed