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Andrew Mackay, PhD

TitleAssociate Professor
InstitutionUniversity of Southern California
DepartmentPharmacology and Pharmaceutical Sciences
AddressPSC 306A
Health Sciences Campus
Los Angeles CA 90089-9121
Phone+1 323 442 4118
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    Collapse Overview 
    Collapse 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.


    Collapse Research 
    Collapse Research Activities and Funding
    Protein-polymer nanomedicine for Sjogren's Syndrome
    NIH/NEI R01EY026635Mar 1, 2017 - Feb 28, 2022
    Role: Co-Principal Investigator
    Intracellular switching using genetically engineered protein microdomains
    NIH/NIGMS R01GM114839Apr 1, 2015 - Mar 31, 2020
    Role: Principal Investigator
    A rapid, reversible switch for controlling intracellular trafficking
    NIH/NIBIB R21EB012281Jul 1, 2010 - Jun 30, 2013
    Role: Principal Investigator
    pH sensitive elastin-like-peptides for tumor targeting
    NIH/NCI F32CA123889Jul 1, 2006 - Jun 30, 2008
    Role: Principal Investigator

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    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Peddi S, Pan X, MacKay JA. Intracellular Delivery of Rapamycin From FKBP Elastin-Like Polypeptides Is Consistent With Macropinocytosis. Front Pharmacol. 2018; 9:1184. PMID: 30386244.
      View in: PubMed
    2. Aluri SR, Shi P, Gustafson JA, Wang W, Lin YA, Cui H, Liu S, Conti PS, Li Z, Hu P, Epstein AL, MacKay JA. A hybrid protein-polymer nanoworm potentiates apoptosis better than a monoclonal antibody. ACS Nano. 2014 Mar 25; 8(3):2064-76. PMID: 24484356; PMCID: PMC4004287.
    3. Aluri S, Pastuszka MK, Moses AS, MacKay JA. Elastin-like peptide amphiphiles form nanofibers with tunable length. Biomacromolecules. 2012 Sep 10; 13(9):2645-54. PMID: 22849577; PMCID: PMC3461336.
    4. Sun G, Hsueh PY, Janib SM, Hamm-Alvarez S, MacKay JA. Design and cellular internalization of genetically engineered polypeptide nanoparticles displaying adenovirus knob domain. J Control Release. 2011 Oct 30; 155(2):218-26. PMID: 21699930; PMCID: PMC3196066.
    5. Chen M, McDaniel JR, MacKay JA, Chilkoti, A. .Proceedings of the National Academy of Inventors. Nanoscale Self-Assembly for Delivery of Therapeutics and Imaging Agents. 2011; 1(13):5-25.
    6. Mackay JA, Callahan DJ, Fitzgerald KN, Chilkoti A. Quantitative model of the phase behavior of recombinant pH-responsive elastin-like polypeptides. Biomacromolecules. 2010 Nov 08; 11(11):2873-9. PMID: 20925333.
      View in: PubMed
    7. MacKay JA, Li Z. Theranostic agents that co-deliver therapeutic and imaging agents? Adv Drug Deliv Rev. 2010 Aug 30; 62(11):1003-4. PMID: 20937334.
      View in: PubMed
    8. Pastuszka MK, Mackay JA. Biomolecular engineering of intracellular switches in eukaryotes. J Drug Deliv Sci Technol. 2010 May; 20(3):163-169. PMID: 21209849.
      View in: PubMed
    9. McDaniel JR, Mackay JA, Quiroz FG, Chilkoti A. Recursive directional ligation by plasmid reconstruction allows rapid and seamless cloning of oligomeric genes. Biomacromolecules. 2010 Apr 12; 11(4):944-52. PMID: 20184309; PMCID: PMC2862688.
    10. Liu W, MacKay JA, Dreher MR, Chen M, McDaniel JR, Simnick AJ, Callahan DJ, Zalutsky MR, Chilkoti A. Injectable intratumoral depot of thermally responsive polypeptide-radionuclide conjugates delays tumor progression in a mouse model. J Control Release. 2010 May 21; 144(1):2-9. PMID: 20117157; PMCID: PMC2862899.
    11. Gao W, Liu W, Mackay JA, Zalutsky MR, Toone EJ, Chilkoti A. In situ growth of a stoichiometric PEG-like conjugate at a protein's N-terminus with significantly improved pharmacokinetics. Proc Natl Acad Sci U S A. 2009 Sep 08; 106(36):15231-6. PMID: 19706892.
      View in: PubMed
    12. Wu Y, MacKay JA, McDaniel JR, Chilkoti A, Clark RL. Fabrication of elastin-like polypeptide nanoparticles for drug delivery by electrospraying. Biomacromolecules. 2009 Jan 12; 10(1):19-24. PMID: 19072041; PMCID: PMC2820340.
    13. Mackay JA, Chilkoti A. Temperature sensitive peptides: engineering hyperthermia-directed therapeutics. Int J Hyperthermia. 2008 Sep; 24(6):483-95. PMID: 18608590; PMCID: PMC2820342.
    14. MacKay JA, Li W, Huang Z, Dy EE, Huynh G, Tihan T, Collins R, Deen DF, Szoka FC. HIV TAT peptide modifies the distribution of DNA nanolipoparticles following convection-enhanced delivery. Mol Ther. 2008 May; 16(5):893-900. PMID: 18388927.
      View in: PubMed
    15. Lim DW, Trabbic-Carlson K, Mackay JA, Chilkoti A. Improved non-chromatographic purification of a recombinant protein by cationic elastin-like polypeptides. Biomacromolecules. 2007 May; 8(5):1417-24. PMID: 17407348; PMCID: PMC2562536.
    16. Chilkoti A, Christensen T, MacKay JA. Stimulus responsive elastin biopolymers: Applications in medicine and biotechnology. Curr Opin Chem Biol. 2006 Dec; 10(6):652-7. PMID: 17055770; PMCID: PMC3732176.
    17. Huang Z, Guo X, Li W, MacKay JA, Szoka FC. Acid-triggered transformation of diortho ester phosphocholine liposome. J Am Chem Soc. 2006 Jan 11; 128(1):60-1. PMID: 16390121; PMCID: PMC3280609.
    18. Lee CC, MacKay JA, Fr├ęchet JM, Szoka FC. Designing dendrimers for biological applications. Nat Biotechnol. 2005 Dec; 23(12):1517-26. PMID: 16333296.
      View in: PubMed
    19. Huang Z, Li W, MacKay JA, Szoka FC. Thiocholesterol-based lipids for ordered assembly of bioresponsive gene carriers. Mol Ther. 2005 Mar; 11(3):409-17. PMID: 15727937.
      View in: PubMed
    20. Krylova IN, Sablin EP, Moore J, Xu RX, Waitt GM, MacKay JA, Juzumiene D, Bynum JM, Madauss K, Montana V, Lebedeva L, Suzawa M, Williams JD, Williams SP, Guy RK, Thornton JW, Fletterick RJ, Willson TM, Ingraham HA. Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1. Cell. 2005 Feb 11; 120(3):343-55. PMID: 15707893.
      View in: PubMed
    21. MacKay JA, Deen DF, Szoka FC. Distribution in brain of liposomes after convection enhanced delivery; modulation by particle charge, particle diameter, and presence of steric coating. Brain Res. 2005 Feb 28; 1035(2):139-53. PMID: 15722054.
      View in: PubMed
    22. Li W, Huang Z, MacKay JA, Grube S, Szoka FC. Low-pH-sensitive poly(ethylene glycol) (PEG)-stabilized plasmid nanolipoparticles: effects of PEG chain length, lipid composition and assembly conditions on gene delivery. J Gene Med. 2005 Jan; 7(1):67-79. PMID: 15515149.
      View in: PubMed
    23. Guo X, MacKay JA, Szoka FC. Mechanism of pH-triggered collapse of phosphatidylethanolamine liposomes stabilized by an ortho ester polyethyleneglycol lipid. Biophys J. 2003 Mar; 84(3):1784-95. PMID: 12609880; PMCID: PMC1302747.
    24. Choi JS, MacKay JA, Szoka FC. Low-pH-sensitive PEG-stabilized plasmid-lipid nanoparticles: preparation and characterization. Bioconjug Chem. 2003 Mar-Apr; 14(2):420-9. PMID: 12643753.
      View in: PubMed
    25. Mackay JA, Szoka FC. HIV TAT Protein Transduction Domain Mediated Cell Binding and Intracellular Delivery of Nanoparticles. J Dispers Sci Technol. 2003; 24(3):465-473. PMID: 20808712.
      View in: PubMed
    26. Martin I, Shastri VP, Padera RF, Yang J, Mackay AJ, Langer R, Vunjak-Novakovic G, Freed LE. Selective differentiation of mammalian bone marrow stromal cells cultured on three-dimensional polymer foams. J Biomed Mater Res. 2001 May; 55(2):229-35. PMID: 11255174.
      View in: PubMed
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