Biography and Education
J. Andrew MacKay’s research group develops next-generation drug carriers that target disease microenvironments, including those in the anterior or posterior of the eye. They specialize in the use of genetically engineered protein-polymers that: (i) drive self-assembly of peptides and small molecules into nanostructures at physiological temperatures; (ii) through multivalent assembly, enable enhanced interactions with biological targets; and (iii) promote extended retention and activity at target locations. The protein-polymers they are developing are highly innovative, as they are composed entirely from human-derived polypeptides. Protein-polymers are large polypeptides that can serve roles traditionally achieved by synthetic polymers, such as a high molecular weight, a platform for conjugating multiple agents, or assembly of a nanostructure. Biologically inspired by the human gene for tropoelastin, protein-polymers known as elastin-like polypeptides are biodegradable, biocompatible, switchable, and may be seamlessly fused with an array of biologically active peptides, including fragments of crystallin proteins. Protein-polymers are an emerging platform for co-encapsulating drugs and biopharmaceuticals and generating multi-functional targeted drug carriers.
Through peptide-based pharmaceutics, Dr. MacKay’s goal is to design therapeutics that target the eye. He maintains collaboration with Dr. Hamm-Alvarez, which seeks to target the inflamed lacrimal gland (dacryoadenitis) with immunosuppressants. This work is relevant to millions of Americans with Sjogren’s Syndrome. In collaboration with Drs. Hinton and Kannan, he has published two major papers detailing the activity of crystallin-fragment peptide fusions with a model of human retinal pigment epithelial cells and also with the intact murine retina under oxidative stress. This work is relevant to millions of Americans with macular degeneration and diabetic retinopathy. In collaboration with Dr. Laurie, they are exploring a mitogenic peptide from human tears, called lacritin that has activity in the lacrimal gland and at the corneal epithelium. Dr. MacKay’s collaborative group seeks to further these technologies to provide better activity in the eye. In addition, he has significant teaching and research experience in the quantification and interpretation of preclinical and clinical pharmacokinetics in locations including the brain, tumor, blood, eye, liver, and kidney.
Dr. MacKay explore the biophysics and engineering of ‘protein-polymers’ as molecular tools and therapeutics. Protein-polymers are high molecular weight repetitive polypeptides with properties of polymers that can be expressed in cells, fused to functional peptides, and tuned to respond to environmental cues. Composed entirely from genetically engineered materials, their sequence can be precisely tailored at the DNA level. Using these novel materials, hisgroup has recently made significant breakthroughs to assemble microstructures inside living cells that modulate cellular biology, to develop state-of-the art molecular imaging approach called image-driven pharmacokinetics, and to develop novel peptide therapeutics for ocular disease and cancer.
- S.B., Chemical Engineering, Massachusetts Institute of Technology, 1999
- S.B., Biology, Massachusetts Institute of Technology, 1999
- Ph.D., Bioengineering, University of California at San Francisco/Berkeley, 2005
- Post-doc, Biomedical Engineering, Duke University, 2008
Professional society memberships:
- Member, American Association of Pharmaceutical Scientists
- Member, American Chemical Society
- Member, Association for Research in Vision and Ophthalmology
- Member, Society for Controlled Release
- Controlled Release Society Biomimetic Drug Delivery Focus Group Young Investigator Award, 2019
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. (PMC6338443)
Peddi S, Pan X, MacKay JA. Intracellular Delivery of Rapamycin from FKBP Elastin-like Polypeptides is Consistent with Macropinocytosis. Frontiers in Pharmacology. 2018, 9. (PMC6199897)
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 Oct 22. pii: S0168-3659(18)30605-9. (PMC6294338)
Klinngam W, Janga SR, Lee C, Ju Y, Yarber F, Shah M, Guo H, Wang D, MacKay JA, Edman MC, Hamm-Alvarez SF. Inhibition of Cathepsin S Reduces Lacrimal Gland Inflammation and Increases Tear Flow in a Mouse Model of Sjögren’s Syndrome. Sci Rep. 2019 Jul 2;9(1):9559. doi: 10.1038/s41598-019-45966-7. (PMC6606642)
Tyrpak DR, Wang Y, Avila H, Guo H, Fu R, Truong AT, Park M, Okamoto CT, Hamm-Alvarez SF, MacKay JA. Caveolin elastin-like polypeptide fusions mediate temperature-dependent assembly of caveolar microdomains. ACS Biomaterials Science and Engineering. 2019 Nov 22, 2019.