Overview

Dr. Chinnapen’s research focuses on addressing two major problems faced in biotechnological drug development: 1) lack of transport for biologics across the blood-brain-barrier, and 2) lack of oral bioavailability of large therapeutic peptides. His lab is currently developing technology to improve existing approaches to treat rare genetic lysosomal disorders, such as Tay-Sachs and Fabry diseases, and to deliver biologics across cellular barriers (endothelial and epithelial) as a platform approach to treat Type II Diabetes orally. Treatment of lysosomal diseases not only requires the delivery to affected vital organs, such as the heart, kidney and vascular endothelium, but also the crossing of the highly-selective blood-brain-barrier, which is virtually impenetrable for large biomolecules such as proteins. The lab also engages industry partners to help accelerate technology toward proof of concept and employing a broad range of disciplines, from organic chemistry to in vivo biology, Another main goal of the lab is to better understand the cellular mechanisms that underpin transcellular transport. Getting a better understanding in this process will aid in the development of next-in-class biotherapeutics that can cross highly-selective cellular barriers.

Background

Dr. Chinnapen received his PhD in nucleic acid biochemistry from Simon Fraser University in Canada, and postdoctoral training at MIT in the lab of Alice Ting and then Harvard Medical School and Boston Children’s Hospital in the lab of Wayne Lencer, MD. Dr. Chinnapen also served as senior scientist in two biotechnology companies in Cambridge MA, developing biologics that enter the cell and signal to treat various diseases.

Selected Publications

  1. Chinnapen DJ, Hsieh WT, te Welscher YM, Saslowsky DE, Kaoutzani L, Brandsma E, D'Auria L, Park H, Wagner JS, Drake KR, Kang M, Benjamin T, Ullman MD, Costello CE, Kenworthy AK, Baumgart T, Massol RH, Lencer WI. (2012) “Lipid Sorting by Ceramide Structure from Plasma Membrane to ER for the Cholera Toxin Receptor GM1.” Developmental Cell. 23:3, 573-586. Featured in Article “GM1 Gets Sorted” Nat. Chem. Biol (2012) 8, 873. 
  2. te Welscher YM, Chinnapen DJ, Kaoutzani L, Mrsny RJ, Lencer WI. (2014) “Unsaturated glycoceramides as molecular carriers for mucosal drug delivery of GLP-1 analogues.” J. Contr. Release. 175: 72-8. 
  3. D. J.-F. Chinnapen, H. Chinnapen, D. Saslowsky and W.I. Lencer. (2007) “Rafting with Cholera Toxin: Endocytosis and Trafficking from the Plasma Membrane to ER.” (Review) FEMS Microbiol. Lett. 266: 129-137 
  4. D.J.-F. Chinnapen and D. Sen. (2004) “A Deoxyribozyme that Harnesses Light to Repair Thymine Dimers in DNA.” Proceedings of the National Academy of Sciences U.S.A. 101: 65-69. Featured in Article “Light-Triggered DNA Self Repair” Chem. & Eng. News (2004) 82:1, 21.

PUBLICATIONS

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  1. Genetic architecture underlying changes in carotenoid accumulation during the evolution of the blind Mexican cavefish, Astyanax mexicanus. J Exp Zool B Mol Dev Evol. 2020 11; 334(7-8):405-422. View abstract
  2. Conjugation of peptides to short-acyl-chain ceramides for delivery across mucosal cell barriers. Bioorg Med Chem Lett. 2020 04 15; 30(8):127014. View abstract
  3. Transcytosis Assay for Transport of Glycosphingolipids across MDCK-II Cells. Bio Protoc. 2018 Oct 20; 8(20). View abstract
  4. Mucosal absorption of therapeutic peptides by harnessing the endogenous sorting of glycosphingolipids. Elife. 2018 05 31; 7. View abstract
  5. Targeting friend and foe: Emerging therapeutics in the age of gut microbiome and disease. J Microbiol. 2018 Mar; 56(3):183-188. View abstract
  6. Membrane Transport across Polarized Epithelia. Cold Spring Harb Perspect Biol. 2017 Sep 01; 9(9). View abstract
  7. Glycolipid Crosslinking Is Required for Cholera Toxin to Partition Into and Stabilize Ordered Domains. Biophys J. 2016 Dec 20; 111(12):2547-2550. View abstract
  8. Microtubule motors power plasma membrane tubulation in clathrin-independent endocytosis. Traffic. 2015 Jun; 16(6):572-90. View abstract
  9. Unsaturated glycoceramides as molecular carriers for mucosal drug delivery of GLP-1. J Control Release. 2014 Feb 10; 175:72-8. View abstract
  10. Ganglioside GM1-mediated transcytosis of cholera toxin bypasses the retrograde pathway and depends on the structure of the ceramide domain. J Biol Chem. 2013 Sep 06; 288(36):25804-25809. View abstract
  11. Lipid sorting by ceramide structure from plasma membrane to ER for the cholera toxin receptor ganglioside GM1. Dev Cell. 2012 Sep 11; 23(3):573-86. View abstract
  12. Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins. Front Cell Infect Microbiol. 2012; 2:51. View abstract
  13. Direct interaction between an allosteric agonist pepducin and the chemokine receptor CXCR4. J Am Chem Soc. 2011 Oct 12; 133(40):15878-81. View abstract
  14. Discovery of dual-action membrane-anchored modulators of incretin receptors. PLoS One. 2011; 6(9):e24693. View abstract
  15. Intracellular phosphatidylserine is essential for retrograde membrane traffic through endosomes. Proc Natl Acad Sci U S A. 2011 Sep 20; 108(38):15846-51. View abstract
  16. Intoxication of zebrafish and mammalian cells by cholera toxin depends on the flotillin/reggie proteins but not Derlin-1 or -2. J Clin Invest. 2010 Dec; 120(12):4399-4409. View abstract
  17. Cholera toxin: an intracellular journey into the cytosol by way of the endoplasmic reticulum. Toxins (Basel). 2010 03; 2(3):310-25. View abstract
  18. Toxins. Cholera Toxin: An Intracellular Journey into the Cytosol by Way of the Endoplasmic Reticulum. 2010; 3:310-325. View abstract
  19. A deoxyribozyme, Sero1C, uses light and serotonin to repair diverse pyrimidine dimers in DNA. J Mol Biol. 2009 Apr 24; 388(1):21-9. View abstract
  20. Rafting with cholera toxin: endocytosis and trafficking from plasma membrane to ER. FEMS Microbiol Lett. 2007 Jan; 266(2):129-37. View abstract
  21. Towards elucidation of the mechanism of UV1C, a deoxyribozyme with photolyase activity. J Mol Biol. 2007 Feb 02; 365(5):1326-36. View abstract
  22. A monovalent streptavidin with a single femtomolar biotin binding site. Nat Methods. 2006 Apr; 3(4):267-73. View abstract
  23. Pure and Applied Chemistry. Structure-Function Investigation of a Deoxyribozyme with Dual Chelatase and Peroxidase Activities. 2004; 76:1537-1545. View abstract
  24. A deoxyribozyme that harnesses light to repair thymine dimers in DNA. Proc Natl Acad Sci U S A. 2004 Jan 06; 101(1):65-9. View abstract
  25. Deoxyribozymes that catalyze photochemistry: cofactor-dependent and -independent photorepair of thymine dimers. Nucleic Acids Res Suppl. 2003; (3):217-8. View abstract
  26. Hemin-stimulated docking of cytochrome c to a hemin-DNA aptamer complex. Biochemistry. 2002 Apr 23; 41(16):5202-12. View abstract