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

  • FLT3/CD99 Bispecific Antibody-Based Nanoparticles for Acute Myeloid Leukemia. Cancer Res Commun. 2024 08 01; 4(8):1946-1962.. View in PubMed
  • Synergy between Laminin-Derived Elastin-like Polypeptides (LELPs) Optimizes Cell Spreading. Biomacromolecules. 2024 07 08; 25(7):4001-4013.. View in PubMed
  • Steric stabilization of bioactive nanoparticles using elastin-like polypeptides. Adv Drug Deliv Rev. 2024 03; 206:115189.. View in PubMed
  • Noncovalent Conjugation of OVA323 to ELP Micelles Increases Immune Response. Biomacromolecules. 2024 02 12; 25(2):1027-1037.. View in PubMed
  • Pharmacokinetic model of human exposure to ciprofloxacin through consumption of fish. Environ Toxicol Pharmacol. 2024 Mar; 106:104359.. View in PubMed
  • αB-Crystallin Peptide Fused with Elastin-like Polypeptide: Intracellular Activity in Retinal Pigment Epithelial Cells Challenged with Oxidative Stress. Antioxidants (Basel). 2023 Sep 30; 12(10).. View in PubMed
  • Biomimetic SARS-CoV-2 Spike Protein Nanoparticles. Biomacromolecules. 2023 05 08; 24(5):2030-2041.. View in PubMed
  • Bet v 1-displaying elastin-like polypeptide nanoparticles induce a strong humoral and weak CD4+ T-cell response against Bet v 1 in a murine immunogenicity model. Front Immunol. 2022; 13:1006776.. View in PubMed
  • Protein and polypeptide mediated delivery to the eye. Adv Drug Deliv Rev. 2022 09; 188:114441.. View in PubMed
  • Hydra-Elastin-like Polypeptides Increase Rapamycin Potency When Targeting Cell Surface GRP78. Biomacromolecules. 2022 08 08; 23(8):3116-3129.. View in PubMed