Education

M.D., Thomas Jefferson University, Jefferson College of Medicine, Philadelphia, PA, USA, 1973

Current position

Professor, Internal Medicine and Gastroenterolgy, Biochemistry/Molecular BIology, Pharmacology, Mayo Clinic, Scottsdale, AZ, USA

Publications （since 2012）

1. Ramil, C. P., Dong, M., An, P., Lewandowski, T. M., Yu, Z., Miller, L. J. and Lin, Q. (2017). Spirohexene-Tetrazine Ligation Enables Bioorthogonal Labeling of Class B G Protein-Coupled Receptors in Live Cells. J Am Chem Soc 139(38): 13376-13386.

2. Yan, Y., Xu, T. H., Harikumar, K. G., Miller, L. J., Melcher, K. and Xu, H. E. (2017). Dimerization of the transmembrane domain of amyloid precursor protein is determined by residues around the gamma-secretase cleavage sites. J Biol Chem 292(38): 15826-15837.

3. Desai, A. J., Dong, M., Langlais, B. T., Dueck, A. C. and Miller, L. J. (2017). Cholecystokinin responsiveness varies across the population dependent on metabolic phenotype. Am J Clin Nutr 106(2): 447-456.

4. DeBruine, Z. J., Ke, J., Harikumar, K. G., Gu, X., Borowsky, P., Williams, B. O., Xu, W., Miller, L. J., Xu, H. E. and Melcher, K. (2017). Wnt5a promotes Frizzled-4 signalosome assembly by stabilizing cysteine-rich domain dimerization. Genes Dev 31(9): 916-926.

5. Liang, Y. L., Khoshouei, M., Radjainia, M., Zhang, Y., Glukhova, A., Tarrasch, J., Thal, D. M., Furness, S. G. B., Christopoulos, G., Coudrat, T., Danev, R., Baumeister, W., Miller, L. J., Christopoulos, A., Kobilka, B. K., Wootten, D., Skiniotis, G. and Sexton, P. M. (2017). Phase-plate cryo-EM structure of a class B GPCR-G-protein complex. Nature 546(7656): 118-123.

6. Harikumar, K. G., Lau, S., Sexton, P. M., Wootten, D. and Miller, L. J. (2017). Coexpressed Class B G Protein-Coupled Secretin and GLP-1 Receptors Self- and Cross-Associate: Impact on Pancreatic Islets. Endocrinology 158(6): 1685-1700.

7. Ward, R. J., Pediani, J. D., Harikumar, K. G., Miller, L. J. and Milligan, G. (2017). Spatial intensity distribution analysis quantifies the extent and regulation of homodimerization of the secretin receptor. Biochem J 474(11): 1879-1895.

8. Wootten, D., Miller, L. J., Koole, C., Christopoulos, A. and Sexton, P. M. (2017). Allostery and Biased Agonism at Class B G Protein-Coupled Receptors. Chem Rev 117(1): 111-138.

9. Desai, A. J., Dong, M., Harikumar, K. G. and Miller, L. J. (2016). Cholecystokinin-induced satiety, a key gut servomechanism that is affected by the membrane microenvironment of this receptor. Int J Obes Suppl 6(Suppl 1): S22-S27.

10. Wootten, D., Reynolds, C. A., Smith, K. J., Mobarec, J. C., Furness, S. G., Miller, L. J., Christopoulos, A. and Sexton, P. M. (2016). Key interactions by conserved polar amino acids located at the transmembrane helical boundaries in Class B GPCRs modulate activation, effector specificity and biased signalling in the glucagon-like peptide-1 receptor. Biochem Pharmacol 118: 68-87.

11. Desai, A. J., Dong, M. and Miller, L. J. (2016). Beneficial effects of beta-sitosterol on type 1 cholecystokinin receptor dysfunction induced by elevated membrane cholesterol. Clin Nutr 35(6): 1374-1379.

12. Ng, H. K., Harikumar, K. G., Miller, L. J. and Chow, B. K. (2016). Signaling Modification by GPCR Heteromer and Its Implication on X-Linked Nephrogenic Diabetes Insipidus. PLoS One 11(9): e0163086.

13. Harikumar, K. G., Augustine, M. L., Lee, L. T., Chow, B. K. and Miller, L. J. (2016). Structure and Function of Cross-class Complexes of G Protein-coupled Secretin and Angiotensin 1a Receptors. J Biol Chem 291(33): 17332-17344.

14. Wootten, D., Reynolds, C. A., Smith, K. J., Mobarec, J. C., Koole, C., Savage, E. E., Pabreja, K., Simms, J., Sridhar, R., Furness, S. G. B., Liu, M., Thompson, P. E., Miller, L. J., Christopoulos, A. and Sexton, P. M. (2016). The Extracellular Surface of the GLP-1 Receptor Is a Molecular Trigger for Biased Agonism. Cell 165(7): 1632-1643.

15. Dong, M., Lam, P. C., Orry, A., Sexton, P. M., Christopoulos, A., Abagyan, R. and Miller, L. J. (2016). Use of Cysteine Trapping to Map Spatial Approximations between Residues Contributing to the Helix N-capping Motif of Secretin and Distinct Residues within Each of the Extracellular Loops of Its Receptor. J Biol Chem 291(10): 5172-5184.

16. Graaf, C., Donnelly, D., Wootten, D., Lau, J., Sexton, P. M., Miller, L. J., Ahn, J. M., Liao, J., Fletcher, M. M., Yang, D., Brown, A. J., Zhou, C., Deng, J. and Wang, M. W. (2016). Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March to Therapeutic Successes. Pharmacol Rev 68(4): 954-1013.

17. Miller, L. J. and Desai, A. J. (2016). Metabolic Actions of the Type 1 Cholecystokinin Receptor: Its Potential as a Therapeutic Target. Trends Endocrinol Metab 27(9): 609-619.

18. Wootten, D., Reynolds, C. A., Koole, C., Smith, K. J., Mobarec, J. C., Simms, J., Quon, T., Coudrat, T., Furness, S. G., Miller, L. J., Christopoulos, A. and Sexton, P. M. (2016). A Hydrogen-Bonded Polar Network in the Core of the Glucagon-Like Peptide-1 Receptor Is a Fulcrum for Biased Agonism: Lessons from Class B Crystal Structures. Mol Pharmacol 89(3): 335-347.

19. Desai, A. J., Lam, P. C., Orry, A., Abagyan, R., Christopoulos, A., Sexton, P. M. and Miller, L. J. (2015). Molecular Mechanism of Action of Triazolobenzodiazepinone Agonists of the Type 1 Cholecystokinin Receptor. Possible Cooperativity across the Receptor Homodimeric Complex. J Med Chem 58(24): 9562-9577.

20. Desai, A. J., Dong, M., Harikumar, K. G. and Miller, L. J. (2015). Impact of ursodeoxycholic acid on a CCK1R cholesterol-binding site may contribute to its positive effects in digestive function. Am J Physiol Gastrointest Liver Physiol 309(5): G377-386.

21. Desai, A. J., Henke, B. R. and Miller, L. J. (2015). Elimination of a cholecystokinin receptor agonist 'trigger' in an effort to develop positive allosteric modulators without intrinsic agonist activity. Bioorg Med Chem Lett 25(9): 1849-1855.

22. Koole, C., Wootten, D., Simms, J., Miller, L. J., Christopoulos, A. and Sexton, P. M. (2015). Differential impact of amino acid substitutions on critical residues of the human glucagon-like peptide-1 receptor involved in peptide activity and small-molecule allostery. J Pharmacol Exp Ther 353(1): 52-63.

23. Dong, M., Vattelana, A. M., Lam, P. C., Orry, A. J., Abagyan, R., Christopoulos, A., Sexton, P. M., Haines, D. R. and Miller, L. J. (2015). Development of a highly selective allosteric antagonist radioligand for the type 1 cholecystokinin receptor and elucidation of its molecular basis of binding. Mol Pharmacol 87(1): 130-140.

24. Miller, L. J., Sexton, P. M., Dong, M. and Harikumar, K. G. (2014). The class B G-protein-coupled GLP-1 receptor: an important target for the treatment of type-2 diabetes mellitus. Int J Obes Suppl 4(Suppl 1): S9-S13.

25. Dong, M., Koole, C., Wootten, D., Sexton, P. M. and Miller, L. J. (2014). Structural and functional insights into the juxtamembranous amino-terminal tail and extracellular loop regions of class B GPCRs. Br J Pharmacol 171(5): 1085-1101.

26. Desai, A. J., Harikumar, K. G. and Miller, L. J. (2014). A type 1 cholecystokinin receptor mutant that mimics the dysfunction observed for wild type receptor in a high cholesterol environment. J Biol Chem 289(26): 18314-18326.

27. Lee, L. T., Ng, S. Y., Chu, J. Y., Sekar, R., Harikumar, K. G., Miller, L. J. and Chow, B. K. (2014). Transmembrane peptides as unique tools to demonstrate the in vivo action of a cross-class GPCR heterocomplex. FASEB J 28(6): 2632-2644.

28. Koole, C., Savage, E. E., Christopoulos, A., Miller, L. J., Sexton, P. M. and Wootten, D. (2013). Minireview: Signal bias, allosterism, and polymorphic variation at the GLP-1R: implications for drug discovery. Mol Endocrinol 27(8): 1234-1244.

29. Miller, L. J. (2013). Molecular basis of peptide activation of the GLP-1 receptor. Mol Metab 2(2): 60-61.

30. Koole, C., Pabreja, K., Savage, E. E., Wootten, D., Furness, S. G., Miller, L. J., Christopoulos, A. and Sexton, P. M. (2013). Recent advances in understanding GLP-1R (glucagon-like peptide-1 receptor) function. Biochem Soc Trans 41(1): 172-179.

31. Miller, L. J. and Dong, M. (2013). The orthosteric agonist-binding pocket in the prototypic class B G-protein-coupled secretin receptor. Biochem Soc Trans 41(1): 154-158.

32. Desai, A. J. and Miller, L. J. (2012). Sensitivity of cholecystokinin receptors to membrane cholesterol content. Front Endocrinol (Lausanne) 3: 123.

33. Ke, J., Harikumar, K. G., Erice, C., Chen, C., Gu, X., Wang, L., Parker, N., Cheng, Z., Xu, W., Williams, B. O., Melcher, K., Miller, L. J. and Xu, H. E. (2013). Structure and function of Norrin in assembly and activation of a Frizzled 4-Lrp5/6 complex. Genes Dev 27(21): 2305-2319.

34. Harikumar, K. G., Cawston, E. E., Lam, P. C., Patil, A., Orry, A., Henke, B. R., Abagyan, R., Christopoulos, A., Sexton, P. M. and Miller, L. J. (2013). Molecular basis for benzodiazepine agonist action at the type 1 cholecystokinin receptor. J Biol Chem 288(29): 21082-21095.

35. Dong, M. and Miller, L. J. (2013). Direct demonstration of unique mode of natural peptide binding to the type 2 cholecystokinin receptor using photoaffinity labeling. Peptides 46: 143-149.\

36. Lomberk, G., Grzenda, A., Mathison, A., Escande, C., Zhang, J. S., Calvo, E., Miller, L. J., Iovanna, J., Chini, E. N., Fernandez-Zapico, M. E. and Urrutia, R. (2013). Kruppel-like factor 11 regulates the expression of metabolic genes via an evolutionarily conserved protein interaction domain functionally disrupted in maturity onset diabetes of the young. J Biol Chem 288(24): 17745-17758.

37. Wootten, D., Simms, J., Miller, L. J., Christopoulos, A. and Sexton, P. M. (2013). Polar transmembrane interactions drive formation of ligand-specific and signal pathway-biased family B G protein-coupled receptor conformations. Proc Natl Acad Sci U S A 110(13): 5211-5216.

38. Harikumar, K. G., Potter, R. M., Patil, A., Echeveste, V. and Miller, L. J. (2013). Membrane cholesterol affects stimulus-activity coupling in type 1, but not type 2, CCK receptors: use of cell lines with elevated cholesterol. Lipids 48(3): 231-244.

39. Dong, M., Pinon, D. I. and Miller, L. J. (2013). Insights into the impact of phenolic residue incorporation at each position along secretin for receptor binding and biological activity. Regul Pept 180: 5-11.

40. Qi, T., Dong, M., Watkins, H. A., Wootten, D., Miller, L. J. and Hay, D. L. (2013). Receptor activity-modifying protein-dependent impairment of calcitonin receptor splice variant Delta(1-47)hCT((a)) function. Br J Pharmacol 168(3): 644-657.

41. Miller, L. J., Dong, M. and Harikumar, K. G. (2012). Ligand binding and activation of the secretin receptor, a prototypic family B G protein-coupled receptor. Br J Pharmacol 166(1): 18-26.

42. Dong, M., Xu, X., Ball, A. M., Makhoul, J. A., Lam, P. C., Pinon, D. I., Orry, A., Sexton, P. M., Abagyan, R. and Miller, L. J. (2012). Mapping spatial approximations between the amino terminus of secretin and each of the extracellular loops of its receptor using cysteine trapping. FASEB J 26(12): 5092-5105.

43. Harikumar, K. G., Wootten, D., Pinon, D. I., Koole, C., Ball, A. M., Furness, S. G., Graham, B., Dong, M., Christopoulos, A., Miller, L. J. and Sexton, P. M. (2012). Glucagon-like peptide-1 receptor dimerization differentially regulates agonist signaling but does not affect small molecule allostery. Proc Natl Acad Sci U S A 109(45): 18607-18612.

44. Te, J. A., Dong, M., Miller, L. J. and Bordner, A. J. (2012). Predicting the effects of amino acid replacements in peptide hormones on their binding affinities for class B GPCRs and application to the design of secretin receptor antagonists. J Comput Aided Mol Des 26(7): 835-845.

45. Cawston, E. E., Lam, P. C., Harikumar, K. G., Dong, M., Ball, A. M., Augustine, M. L., Akgun, E., Portoghese, P. S., Orry, A., Abagyan, R., Sexton, P. M. and Miller, L. J. (2012). Molecular basis for binding and subtype selectivity of 1,4-benzodiazepine antagonist ligands of the cholecystokinin receptor. J Biol Chem 287(22): 18618-18635.

46. Ke, J., Zhang, C., Harikumar, K. G., Zylstra-Diegel, C. R., Wang, L., Mowry, L. E., Miller, L. J., Williams, B. O. and Xu, H. E. (2012). Modulation of beta-catenin signaling by glucagon receptor activation. PLoS One 7(3): e33676.

47. Garcia, G. L., Dong, M. and Miller, L. J. (2012). Differential determinants for coupling of distinct G proteins with the class B secretin receptor. Am J Physiol Cell Physiol 302(8): C1202-1212.

48. Koole, C., Wootten, D., Simms, J., Savage, E. E., Miller, L. J., Christopoulos, A. and Sexton, P. M. (2012). Second extracellular loop of human glucagon-like peptide-1 receptor (GLP-1R) differentially regulates orthosteric but not allosteric agonist binding and function. J Biol Chem 287(6): 3659-3673.

49. Koole, C., Wootten, D., Simms, J., Miller, L. J., Christopoulos, A. and Sexton, P. M. (2012). Second extracellular loop of human glucagon-like peptide-1 receptor (GLP-1R) has a critical role in GLP-1 peptide binding and receptor activation. J Biol Chem 287(6): 3642-3658.

50. Cawston, E. E., Harikumar, K. G. and Miller, L. J. (2012). Ligand-induced internalization of the type 1 cholecystokinin receptor independent of recognized signaling activity. Am J Physiol Cell Physiol 302(3): C615-627.

51. Potter, R. M., Harikumar, K. G., Wu, S. V. and Miller, L. J. (2012). Differential sensitivity of types 1 and 2 cholecystokinin receptors to membrane cholesterol. J Lipid Res 53(1): 137-148.

52. Dong, M., Pinon, D. I. and Miller, L. J. (2012). Site of action of a pentapeptide agonist at the glucagon-like peptide-1 receptor. Insight into a small molecule agonist-binding pocket. Bioorg Med Chem Lett 22(1): 638-641.