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

  • Supra-lacrimal protein-based carriers for cyclosporine A reduce Th17-mediated autoimmunity in murine model of Sjögren’s syndrome. Biomaterials. 2022 04; 283:121441.. View in PubMed
  • Intracellular Dynamin Elastin-like Polypeptides Assemble into Rodlike, Spherical, and Reticular Dynasomes. Biomacromolecules. 2022 01 10; 23(1):265-275.. View in PubMed
  • Single-Cell Quantification of the Transition Temperature of Intracellular Elastin-like Polypeptides. ACS Biomater Sci Eng. 2021 02 08; 7(2):428-440.. View in PubMed
  • Intralacrimal Sustained Delivery of Rapamycin Shows Therapeutic Effects without Systemic Toxicity in a Mouse Model of Autoimmune Dacryoadenitis Characteristic of Sjögren’s Syndrome. Biomacromolecules. 2021 03 08; 22(3):1102-1114.. View in PubMed
  • SIAL: A simple image analysis library for wet-lab scientists. J Open Source Softw. 2020; 5(56).. View in PubMed
  • Live long and active: Polypeptide-mediated assembly of antibody variable fragments. Adv Drug Deliv Rev. 2020 12; 167:1-18.. View in PubMed
  • Adaptable antibody Nanoworms designed for non-Hodgkin lymphoma. Biomaterials. 2020 12; 262:120338.. View in PubMed
  • Biosynthesized Multivalent Lacritin Peptides Stimulate Exosome Production in Human Corneal Epithelium. Int J Mol Sci. 2020 Aug 26; 21(17).. View in PubMed
  • Berunda Polypeptides Carrying Rapalogues Inhibit Tumor mTORC1 Better than Oral Everolimus. Biomacromolecules. 2020 08 10; 21(8):3038-3046.. View in PubMed
  • Anti-CD99 scFv-ELP nanoworms for the treatment of acute myeloid leukemia. Nanomedicine. 2020 10; 29:102236.. View in PubMed