Eric Appel

Eric A. Appel, PhD, Associate Professor, Department of Material Science & Engineering, Stanford University School of Engineering; Associate Professor (by courtesy), Department of Bioengineering, Stanford University School of Engineering; Associate Professor (by courtesy), Department of Pediatrics, Division of Endocrinology, Stanford University School of Medicine; Senior Fellow (by courtesy), the Woods Institute for the Environment; Faculty Fellow, ChEM-H Institute

Research description: The Appel lab at Stanford integrates concepts and approaches from supramolecular chemistry and natural/synthetic materials to tackle healthcare challenges of critical importance to society, including diabetes mellitus. They have developed a platform of materials with unique, tunable properties that they are exploiting as the basis for novel treatment strategies for a range of disease targets. Relevant to diabetes, Appel’s group has developed polymer excipient technology affording unprecedented stabilization of monomeric insulin, a strategy that forms the basis of novel ultra-fast-acting insulin formulations for treatment of diabetes. They have also developed a polymer excipient platform to develop a stable co-formulation of insulin and amylin analogues as a dual-hormone therapy for treatment of diabetes. They have several on-going collaborations with multiple members of SDRC that focus on the translation of their new material technologies.

Selected relevant publications (SDRC Members in BOLD):

  1. Maikawa CL, Smith AAA, Zou L, Roth GA, Gale EC, Stapleton LM, Baker SW, Mann JL, Yu AC, Correa S, Grosskopf AK, Liong CS, Meis CM, Chan D, Troxell M, Maahs DM, Buckingham BA, Webber MJ, Appel EA. A co-formulation of supramolecularly stabilized insulin and pramlintide enhances mealtime glucagon suppression in diabetic pigs. Nat Biomed Eng. 2020 May;4(5):507-517. doi: 10.1038/s41551-020-0555-4. PMID: 32393892; PMCID: PMC7274092.

  2. Smith AAA, Maikawa CL, Roth GA, Appel EA. Site-selective modification of proteins using cucurbit[7]uril as supramolecular protection for N-terminal aromatic amino acids. Org Biomol Chem. 2020 May 27. doi: 10.1039/d0ob01004a. PMID: 32459261.

  3. Maikawa CL, Smith AAA, Zou L, Meis CM, Mann JL, Webber MJ, Appel EA. Stable Monomeric Insulin Formulations Enabled by Supramolecular PEGylation of Insulin Analogues. Adv Ther (Weinh). 2020 Jan;3(1):1900094. doi: 10.1002/adtp.201900094. PMID: 32190729; PMCID: PMC7079736.

  4. Mann JL, Maikawa CL, Smith AAA, Grosskopf AK, Baker SW, Roth GA, Meis CM, Gale EC, Liong CS, Correa S, Chan D, Stapleton LM, Yu AC, Muir B, Howard S, Postma A, Appel EA. An ultrafast insulin formulation enabled by high-throughput screening of engineered polymeric excipients. Sci Transl Med. 2020 Jul 1;12(550):eaba6676. doi: 10.1126/scitranslmed.aba6676. PMID: 32611683; PMCID: PMC7716884.

  5. Maikawa CL, d'Aquino AI, Lal RA, Buckingham BA, Appel EA. Engineering biopharmaceutical formulations to improve diabetes management. Sci Transl Med. 2021 Jan 27;13(578):eabd6726. doi: 10.1126/scitranslmed.abd6726. PMID: 33504649; PMCID: PMC8004356. 

  6. Poudineh M, Maikawa CL, Ma EY, Pan J, Mamerow D, Hang Y, Baker SW, Beirami A, Yoshikawa A, Eisenstein M, Kim S, Vučković J, Appel EA, Soh HT. A fluorescence sandwich immunoassay for the real-time continuous detection of glucose and insulin in live animals. Nat Biomed Eng. 2021 Jan;5(1):53-63. doi: 10.1038/s41551-020-00661-1. Epub 2020 Dec 21. PMID: 33349659; PMCID: PMC7856282. 

  7. Meis CM, Salzman EE, Maikawa CL, Smith AAA, Mann JL, Grosskopf AK, Appel EA. Self-Assembled, Dilution-Responsive Hydrogels for Enhanced Thermal Stability of Insulin Biopharmaceuticals. ACS Biomater Sci Eng. 2021 Sep 13;7(9):4221-4229. PMID: 34510910; PMCID: PMC8441967. 

  8. Maikawa CL, Chen PC, Vuong ET, Nguyen LT, Mann JL, d'Aquino AI, Lal RA, Maahs DM, Buckingham BA, Appel EA. Ultra-Fast Insulin-Pramlintide Co-Formulation for Improved Glucose Management in Diabetic Rats. Adv Sci (Weinh). 2021 Sep 9:e2101575. PMID: 34499434. 

  9. Jiang Z, Zhao M, Voilquin L, Jung Y, Aikio MA, Sahai T, Dou FY, Roche AM, Carcamo-Orive I, Knowles JW, Wabitsch M, Appel EA, Maikawa CL, Camporez JP, Shulman GI, Tsai L, Rosen ED, Gardner CD, Spiegelman BM, Svensson KJ. Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis. Cell Metab. 2021 Sep 7;33(9):1836-1852.e11. PMID: 34348115; PMCID: PMC8429235. 

  10. Maikawa CL, d'Aquino AI, Vuong ET, Su B, Zou L, Chen PC, Nguyen LT, Autzen AAA, Mann JL, Webber MJ, Appel EA. Affinity-Directed Dynamics of Host-Guest Motifs for Pharmacokinetic Modulation via Supramolecular PEGylation. Biomacromolecules. 2021 Aug 9;22(8):3565-3573. PMID: 34314146. 

  11. Maikawa CL, Mann JL, Kannan A, Meis CM, Grosskopf AK, Ou BS, Autzen AAA, Fuller GG, Maahs DM, Appel EA. Engineering Insulin Cold Chain Resilience to Improve Global Access. Biomacromolecules. 2021 Aug 9;22(8):3386-3395. PMID: 34213889. 

  12. Lal RA, Maikawa CL, Lewis D, Baker SW, Smith AAA, Roth GA, Gale EC, Stapleton LM, Mann JL, Yu AC, Correa S, Grosskopf AK, Liong CS, Meis CM, Chan D, Garner JP, Maahs DM, Buckingham BA, Appel EA. Full closed loop open-source algorithm performance comparison in pigs with diabetes. Clin Transl Med. 2021 Apr;11(4):e387. PMID: 33931977; PMCID: PMC8087942. 

  13. Mann JL, Grosskopf AK, Smith AAA, Appel EA. Highly Branched Polydimethylacrylamide Copolymers as Functional Biomaterials. Biomacromolecules. 2021 Jan 11;22(1):86-94. PMID: 32786733; PMCID: PMC7805010. 

  14. Maikawa CL, Nguyen LT, Mann JL, Appel EA. Formulation Excipients and Their Role in Insulin Stability and Association State in Formulation. Pharm Res. 2022 Aug 17. PMID: 35978148. 

  15. d'Aquino AI, Maikawa CL, Nguyen LT, Lu K, Hall IA, Jons CK, Kasse CM, Yan J, Prossnitz AN, Chang E, Baker SW, Hovgaard L, Steensgaard DB, Andersen HB, Simonsen L, Appel EA. Use of a biomimetic hydrogel depot technology for sustained delivery of GLP-1 receptor agonists reduces burden of diabetes management. Cell Rep Med. 2023 Nov 21;4(11):101292. doi: 10.1016/j.xcrm.2023.101292. PMID: 37992687; PMCID: PMC10694761. 

  16. Chan D, Maikawa CL, d'Aquino AI, Raghavan SS, Troxell ML, Appel EA. Polyacrylamide-based hydrogel coatings improve biocompatibility of implanted pump devices. J Biomed Mater Res A. 2023 Mar 2. PMID: 36861657.