J. Andrew MacKay

J. Andrew MacKay, PhD

Associate Professor

Pharmacology and Pharmaceutical Sciences

Research Topics

  1. Drug delivery
  2. Biomolecular engineering
  3. Liposomes
  4. Elastin like polypeptides
  5. Protein polymers,
  6. Nanomedicine

Contact Information

  • jamackay@usc.edu
  • 9121
  • Health Science Campus, PS306
  • (323) 442-4118
  • (323) 442-1390

Education

S.B. 1999 Chemical Engineering and Biology - Massachusetts Institute of Technology

Ph.D. 2005 Bioengineering - University of California at Berkeley/San Francisco
Ph.D. 2005 Bioengineering - University of California at Berkeley/San Francisco

Postdoctoral Research Fellowship:
2005 - 2008 Duke University

Started at USC: December, 2008

J. Andrew MacKay

Research Interest

OVERVIEW
Our lab engineers a new generation of polypeptide-based drug carriers that change physical properties in response to disease microenvironments. Cancer and ocular diseases are our primary focus. The delivery of drugs, both in the eye and throughout the body, is hindered by access and retention at the target site. Many drugs are dose-limited by toxicity at peripheral sites in the body. Our goal is to repackage these drugs into bioresponsive nanocarriers (10-200 nm in diameter), composed from lipids and/or peptides, which activate site-specific drug release and reduce toxicity. Successful carrier strategies are being formulated and evaluated for translation to the clinic.

PROTEIN POLYMERS
Protein polymers are a powerful technology exploited by our group. Some conformations/behaviors found in natural proteins can be recapitulated in repetitive genetically engineered peptides, such as leucine zippers, the collagen triple helix, or silkworm silk. A related example from human tropoelastin, the elastin-like-polypeptides (ELPs) are repeats of (Val-Pro-Gly-Xaa-Gly)n. ELPs have characteristic inverse phase transition temperatures above which they rapidly phase separate from bulk solution. A function of peptide sequence and environment, this reversible transition can cycle between soluble and insoluble states, equivalent to an on/off switch. Under isothermal conditions, ELP switches can be engineered for sensitivity to other specific environmental variables, such as pH, ionic strength, and conformation of adjacent proteins. As a pharmacological platform, genetically engineered ELPs are monodisperse, biodegradable, encoded from human self-antigens, and can incorporate specific residues for biological (protein) or chemical (drug) payloads. Our group actively explores design parameters that link environmental cues to peptide phase transitions and applications for these switches in disease microenvironments.

LIPOSOMES
Lipid-based drug carriers are another powerful technology used by our group. Composed of phospholipids similar to those found in cell membranes, liposomes are vesicles with aqueous interiors that can carry a variety of therapeutic cargo. The most prominent liposome-based chemotherapeutic, Doxil TM, consists of doxorubicin within a sterically shielded lipid bilayer. Liposome technology is mature, meaning that a wide platform of compositions, sizes and drug encapsulation methods are achievable. Building on this broad platform, our group explores liposomes coated with bioresponsive peptides that mediate rapid drug accumulation and release in the tumor microenvironment.

FUNDING
Within the past four years, we have been funded by the NIH National Eye Institute, the NIH National Institute of Biomedical Imaging and Bioengineering, the US Army TATRC, the Stop Cancer Foundation, the American Cancer Society, the USC Research Center for Liver Disease, the USC Ming Hsieh Institute, the Whittier Foundation, the Wright Foundation, the SC-CTSI, and the USC School of Pharmacy.

Biography

Dr. MacKay received his S.B. in chemical engineering and biology from the Massachusetts Institute of Technology in 1999. After working for a Boston area biotechnology company, he entered the Joint Graduate Group in Bioengineering at the University of California at San Francisco and Berkeley. At UCSF-Berkeley, he earned a Howard Hughes Medical Institute Predoctoral Fellowship. Upon completing his Ph.D. in 2005, Dr. Mackay joined the Department of Biomedical Engineering at Duke University, where he earned a Kirschstein National Research Service Award Postdoctoral Fellowship. Dr. MacKay joined the faculty in the Department of Pharmaceutical Sciences at the University of Southern California as an Assistant Professor in December 2008.

Selected Projects/Publications

View a complete PubMed search

View a complete Google Scholar search

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. Epub 2012 Aug 21. PubMed

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. doi: 10.1002/pro.2063. Epub 2012 May 14. PubMed

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. Epub 2011 Jun 14. PubMed

Pastuszka MK, MacKay JA. Biomolecular engineering of intracellular switches in eukaryotes. J Drug Deliv Sci Technol. 2010 May;20(3):163-169. PubMed

Janib SM, Moses AS, MacKay JA. Imaging and drug delivery using theranostic nanoparticles. Adv Drug Deliv Rev. 2010 Aug 30;62(11):1052-63. Epub 2010 Aug 13. PubMed

Aluri S, Janib SM, MacKay JA. Environmentally responsive peptides as anticancer drug carriers. Adv Drug Deliv Rev. 2009 Sep 30;61(11):940-52. Epub 2009 Jul 20. PubMed

MacKay JA, Callahan DJ, Fitzgerald KN, Chilkoti A. Quantitative Model of the Phase Behavior of Recombinant pH-Responsive Elastin-Like Polypeptides. Biomacromolecules. 2010 Oct 6. [Epub ahead of print] PubMed

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. Epub 2009 Nov 8. PubMed

MacKay JA, Li W, Huang Z, Dy EE, Huynh G, Tihan T, Collins R, Deen DF, Szoka FC Jr. HIV TAT peptide modifies the distribution of DNA nanolipoparticles following convection-enhanced delivery. Mol Ther. 2008 May;16(5):893-900. Epub 2008 Mar 11. PubMed

Lee CC, MacKay JA, Fréchet JM, Szoka FC. Designing dendrimers for biological applications. Nat Biotechnol. 2005 Dec;23(12):1517-26. PubMed

MacKay JA, Deen DF, Szoka FC Jr. 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. Epub 2005 Jan 28. PubMed

Martin I, Shastri VP, Padera RF, Yang J, Mackay JA, 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. PubMed