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Andrew Mackay, PhD

Title(s)Associate Professor
SchoolSchool of Pharmacy
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.
    List All   |   Timeline
    1. Guo H, Lee C, Shah M, Janga SR, Edman MC, Klinngam W, Hamm-Alvarez SF, MacKay JA. A novel elastin-like polypeptide drug carrier for cyclosporine A improves tear flow in a mouse model of Sjögren's syndrome. J Control Release. 2018 Dec 28; 292:183-195. PMID: 30359668.
      View in: PubMed
    2. 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
    3. Ju Y, Janga SR, Klinngam W, MacKay JA, Hawley D, Zoukhri D, Edman MC, Hamm-Alvarez SF. NOD and NOR mice exhibit comparable development of lacrimal gland secretory dysfunction but NOD mice have more severe autoimmune dacryoadenitis. Exp Eye Res. 2018 Nov; 176:243-251. PMID: 30201519.
      View in: PubMed
    4. Li Z, Tyrpak DR, Park M, Okamoto CT, MacKay JA. A new temperature-dependent strategy to modulate the epidermal growth factor receptor. Biomaterials. 2018 Nov; 183:319-330. PMID: 30196151.
      View in: PubMed
    5. Sreekumar PG, Li Z, Wang W, Spee C, Hinton DR, Kannan R, MacKay JA. Intra-vitreal aB crystallin fused to elastin-like polypeptide provides neuroprotection in a mouse model of age-related macular degeneration. J Control Release. 2018 Aug 10; 283:94-104. PMID: 29778783.
      View in: PubMed
    6. Dhandhukia JP, Shi P, Peddi S, Li Z, Aluri S, Ju Y, Brill D, Wang W, Janib SM, Lin YA, Liu S, Cui H, MacKay JA. Bifunctional Elastin-like Polypeptide Nanoparticles Bind Rapamycin and Integrins and Suppress Tumor Growth in Vivo. Bioconjug Chem. 2017 11 15; 28(11):2715-2728. PMID: 28937754.
      View in: PubMed
    7. Dhandhukia JP, Brill DA, Kouhi A, Pastuszka MK, MacKay JA. Elastin-like polypeptide switches: A design strategy to detect multimeric proteins. Protein Sci. 2017 Sep; 26(9):1785-1795. PMID: 28639381.
      View in: PubMed
    8. Shah M, Edman MC, Reddy Janga S, Yarber F, Meng Z, Klinngam W, Bushman J, Ma T, Liu S, Louie S, Mehta A, Ding C, MacKay JA, Hamm-Alvarez SF. 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. PMID: 28122086.
      View in: PubMed
    9. Despanie J, Dhandhukia JP, Hamm-Alvarez SF, MacKay JA. Elastin-like polypeptides: Therapeutic applications for an emerging class of nanomedicines. J Control Release. 2016 10 28; 240:93-108. PMID: 26578439.
      View in: PubMed
    10. Brill DA, MacKay JA. Image-driven pharmacokinetics: nanomedicine concentration across space and time. Nanomedicine (Lond). 2015; 10(18):2861-79. PMID: 26370694.
      View in: PubMed
    11. Pastuszka MK, MacKay JA. Engineering structure and function using thermoresponsive biopolymers. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2016 Jan-Feb; 8(1):123-38. PMID: 26112277; PMCID: PMC4732732 [Available on 01/01/17].
    12. Hsueh PY, Edman MC, Sun G, Shi P, Xu S, Lin YA, Cui H, Hamm-Alvarez SF, MacKay JA. Tear-mediated delivery of nanoparticles through transcytosis of the lacrimal gland. J Control Release. 2015 Jun 28; 208:2-13. PMID: 25523518; PMCID: PMC4456098.
    13. Wang W, Despanie J, Shi P, Edman-Woolcott MC, Lin YA, Cui H, Heur JM, Fini ME, Hamm-Alvarez SF, MacKay JA. Lacritin-mediated regeneration of the corneal epithelia by protein polymer nanoparticles. J Mater Chem B. 2014 Dec 14; 2(46):8131-8141. PMID: 25530855.
      View in: PubMed
    14. Wang W, Jashnani A, Aluri SR, Gustafson JA, Hsueh PY, Yarber F, McKown RL, Laurie GW, Hamm-Alvarez SF, MacKay JA. A thermo-responsive protein treatment for dry eyes. J Control Release. 2015 Feb 10; 199:156-67. PMID: 25481446; PMCID: PMC4456095.
    15. Pastuszka MK, Okamoto CT, Hamm-Alvarez SF, MacKay JA. Flipping the Switch on Clathrin-Mediated Endocytosis using Thermally Responsive Protein Microdomains. Adv Funct Mater. 2014 Sep 10; 24(34):5340-5347. PMID: 25419208.
      View in: PubMed
    16. Pastuszka MK, Wang X, Lock LL, Janib SM, Cui H, DeLeve LD, MacKay JA. An amphipathic alpha-helical peptide from apolipoprotein A1 stabilizes protein polymer vesicles. J Control Release. 2014 Oct 10; 191:15-23. PMID: 25016969; PMCID: PMC4327866.
    17. Janib SM, Gustafson JA, Minea RO, Swenson SD, Liu S, Pastuszka MK, Lock LL, Cui H, Markland FS, Conti PS, Li Z, MacKay JA. Multimeric disintegrin protein polymer fusions that target tumor vasculature. Biomacromolecules. 2014 Jul 14; 15(7):2347-58. PMID: 24871936; PMCID: PMC4098058.
    18. Wang W, Sreekumar PG, Valluripalli V, Shi P, Wang J, Lin YA, Cui H, Kannan R, Hinton DR, MacKay JA. Protein polymer nanoparticles engineered as chaperones protect against apoptosis in human retinal pigment epithelial cells. J Control Release. 2014 Oct 10; 191:4-14. PMID: 24780268.
      View in: PubMed
    19. Shi P, Gustafson JA, MacKay JA. Genetically engineered nanocarriers for drug delivery. Int J Nanomedicine. 2014; 9:1617-26. PMID: 24741309; PMCID: PMC3970941.
    20. 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.
    21. Janib SM, Pastuszka M, Aluri S, Folchman-Wagner Z, Hsueh PY, Shi P, Cui H, Mackay JA. A quantitative recipe for engineering protein polymer nanoparticles. Polym Chem. 2014 Jan; 5(5):1614-1625. PMID: 24511327.
      View in: PubMed
    22. Shi P, Lin YA, Pastuszka M, Cui H, Mackay JA. Triggered sorting and co-assembly of genetically engineered protein microdomains in the cytoplasm. Adv Mater. 2014 Jan 22; 26(3):449-54. PMID: 24136711; PMCID: PMC3947098.
    23. Shah M, Edman MC, Janga SR, Shi P, Dhandhukia J, Liu S, Louie SG, Rodgers K, Mackay JA, Hamm-Alvarez SF. 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. PMID: 23892265; PMCID: PMC3796004.
    24. Shi P, Aluri S, Lin YA, Shah M, Edman M, Dhandhukia J, Cui H, MacKay JA. 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. PMID: 23714121; PMCID: PMC3795821.
    25. Dhandhukia J, Weitzhandler I, Wang W, MacKay JA. Switchable elastin-like polypeptides that respond to chemical inducers of dimerization. Biomacromolecules. 2013 Apr 08; 14(4):976-85. PMID: 23406497; PMCID: PMC3721738.
    26. Janib SM, Liu S, Park R, Pastuszka MK, Shi P, Moses AS, Orosco MM, Lin YA, Cui H, Conti PS, Li Z, MacKay JA. Kinetic quantification of protein polymer nanoparticles using non-invasive imaging. Integr Biol (Camb). 2013 Jan; 5(1):183-94. PMID: 23093022; PMCID: PMC3762326.
    27. Pastuszka MK, Janib SM, Weitzhandler I, Okamoto CT, Hamm-Alvarez S, Mackay JA. A tunable and reversible platform for the intracellular formation of genetically engineered protein microdomains. Biomacromolecules. 2012 Nov 12; 13(11):3439-44. PMID: 23088632; PMCID: PMC3500625.
    28. 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.
    29. Shah M, Hsueh PY, Sun G, Chang HY, Janib SM, MacKay JA. Biodegradation of elastin-like polypeptide nanoparticles. Protein Sci. 2012 Jun; 21(6):743-50. PMID: 22434766; PMCID: PMC3403411.
    30. 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.
    31. Chen M, McDaniel JR, Mackay JA, Chilkoti A. NANOSCALE SELF-ASSEMBLY FOR DELIVERY OF THERAPEUTICS AND IMAGING AGENTS. Technol Innov. 2011 Jan 01; 13(1):5-25. PMID: 24077873.
      View in: PubMed
    32. 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.
    33. 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
    34. 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
    35. Janib SM, Moses AS, MacKay JA. Imaging and drug delivery using theranostic nanoparticles. Adv Drug Deliv Rev. 2010 Aug 30; 62(11):1052-1063. PMID: 20709124; PMCID: PMC3769170.
    36. 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
    37. 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.
    38. 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.
    39. MacKay JA, Chen M, McDaniel JR, Liu W, Simnick AJ, Chilkoti A. Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection. Nat Mater. 2009 Dec; 8(12):993-9. PMID: 19898461; PMCID: PMC2862348.
    40. 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
    41. Aluri S, Janib SM, Mackay JA. Environmentally responsive peptides as anticancer drug carriers. Adv Drug Deliv Rev. 2009 Sep 30; 61(11):940-52. PMID: 19628014; PMCID: PMC2757494.
    42. 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.
    43. Mackay JA, Chilkoti A. Temperature sensitive peptides: engineering hyperthermia-directed therapeutics. Int J Hyperthermia. 2008 Sep; 24(6):483-95. PMID: 18608590; PMCID: PMC2820342.
    44. 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
    45. 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.
    46. 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.
    47. 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.
    48. Lee CC, MacKay JA, Fréchet JM, Szoka FC. Designing dendrimers for biological applications. Nat Biotechnol. 2005 Dec; 23(12):1517-26. PMID: 16333296.
      View in: PubMed
    49. 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
    50. 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
    51. 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
    52. 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
    53. 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.
    54. 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
    55. 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
    56. 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