Emmanuelle J. Meuillet, PhD

Associate Research Professor, Nutritional Sciences

E-Mail Address: 
Phone Number: 
(520) 626-5794
Short Bio: 

Dr. Meuillet recieved her PhD in Biochemistry and Pharmacology from the University Louis Pasteur, Strasbourg (France) in 1995. She completed post-doctoral training at the Childrens' Memorial Hospital at Northwestern University (Chicago, IL) in 1999 and at the Arizona Cancer Center (Tucson, AZ) in 2002. Dr. Meuillet's research program has been funded by the National Institute for Health (NIH) since 2002, by the Arizona Sate and by several foundation including the Hirshberg Foundation for Pancreatic Cancer Research. She has co-foundeed Phusis Therapeutics, Inc (San Diego, CA) in 2009 based on her work on AKT. Her interests includes the discovery and development of novel targeted therapies for the treatment of metastases.  

Research Information
Research Program: 
1. Therapeutic Development
Member Status: 
Member
Year of Membership Acceptance: 
2002
Institution: 
University of Arizona Cancer Center
College: 
CALS
Summary of Research Activity: 

Dr Meuillet's interdisciplinary and highly collaborative research program focuses on several aspects of drug discovery and development for the treatment and prevention of metastases. Her group has recently developed inhibitors of Guanine Exchange Factors, which represent novel drug targets for prostate cancer bone metastasis.  Dr. Meuillet studies also the process of inflammation, a driving force of cancer metastasis. 

Selected Publications: 

1. Crémel G, Ficková M, Klimeš I, Leray C, Leray V, Meuillet E, Roques M, Staedel C, Hubert P. (1993) Lipid modulation of insulin receptor tyrosine kinase in cultured cells, animals, and reconstituted systems. In Klimeš I, Howard BV, Storlien LH, Šeböková E, Eds. "Dietary Lipids and Insulin Action: Proceedings of the Second International Smolenice Insulin Symposium". Ann NY Acad Sci 683:164-171.

2. Meuillet EJ, Crémel G, Forster V, Guerold B, Hicks D, Dreyfus H. (1995) GM3 effects on growth factor receptors in the retina. Publication in IPSEN Books. Ophthalmology Meetings, 7:155-163.

3. Meuillet E, Crémel G, Hicks D, Dreyfus H. (1996) Ganglioside effects on basic fibroblast and epidermal growth factor receptors in retinal glial cells. J Lipid Mediat Cell Signal 14(1‑3):277-288.

4. Meuillet E, Crémel G, Dreyfus H, Hicks D. (1996) Differential modulation of basic fibroblast and epidermal growth factor receptor activation by ganglioside GM3 in cultured retinal Muller glia. GLIA 17(3):206-216.

5. Rebbaa A, Yamamoto H, Saito T, Meuillet E, Kim P, Kersey DS, Bremer EG, Taniguchi N, Moskal JR. (1997) Gene transfection-mediated overexpression of beta1,4-N-acetylglucosamine bisecting oligosaccharides in glioma cell line U373 MG inhibits epidermal growth factor receptor function. J Biol Chem 272(14):9275-9279.

6. Meuillet E, Wiernsperger N, Hubert P, Crémel G. (1997) Biguanide effects on insulin signaling. In Klimes I, Haffner SM, Šeböková E, Howard BV, Storlein LH, Eds. “Lipids and Syndromes of Insulin Resistance: From Molecular Biology to Clinical Medicine”. Ann NY Acad Sci827:546-549.

7. Dreyfus H, Meuillet E, Guerold B, Fontaine V, Forster V, Heidinger V, Sahel J, Hicks D. (1997) Ganglioside and neurotrophic growth factor interactions in retinal neuronal and glial cells. Ind J Biochem Biophys 34(1-2):90-96.

8. Meuillet EJ, Bremer EG. (1998) Growth factor receptors as targets for therapy in pediatric brain tumors. Pediatr Neurosurg 29(1):1-13.

9. Dreyfus H, Sahel J, Heidinger V, Mohand-Said S, Guerold B, Meuillet E, Fontaine V, Hicks D. (1998) Gangliosides and neurotrophic growth factors in the retina. Molecular interactions and applications as neuroprotective agents. In Ledeen RW, Hakomori SI, Yates AJ, Schneider JS, Yu RK, Eds. “Sphingolipids as Signaling Modulators in the Nervous System”. Ann NY Acad Sci 845:240-252.

10. Meuillet EJ, Wiernsperger N, Mania-Farnell B, Hubert P, Crémel G. (1999) Metformin modulates insulin receptor signaling in normal and cholesterol-treated human hepatoma cells (HepG2). Eur J Pharmacol 377(2-3):241-252.

11. Meuillet EJ, Leray V, Hubert P, Leray C, Crémel G. (1999) Incorporation of exogenous lipids modulates insulin signaling in the hepatoma cell line, HepG2. Biochim Biophys Acta 1454(1):38-48.

12. Meuillet EJ, Kroes R, Yamamoto H, Warner TG, Ferrari J, Mania-Farnell B, George D, Rebbaa A, Moskal JR, Bremer EG. (1999) Sialidase gene transfection enhances epidermal growth factor receptor activity in an epidermoid carcinoma cell line, A431. Cancer Res 59(1):234-240.

13. Meuillet EJ, Mania-Farnell B, George D, Inokuchi JI, Bremer EG. (2000) Modulation of EGF receptor activity by changes in the GM3 content in a human epidermoid carcinoma cell line, A431. Exp Cell Res 256(1):74-82.

14. Hu YH, Meuillet EJ, Qiao LX, Berggren MM, Powis G, Kozikowski AP. (2000) Synthesis and Akt inhibitory properties of a 1D-3,4-dideoxyphosphatidyl-inositol ether lipid. Tetrahedron Lett 41(39):7415-7418.

15. Hu Y, Qiao L, Wang S, Rong SB, Meuillet EJ, Berggren M, Gallegos A, Powis G, Kozikowski AP. (2000) 3-(Hydroxymethyl)-bearing phosphatidylinositol ether lipid analogues and carbonate surrogates block PI3-K, Akt, and cancer cell growth. J Med Chem 43(16):3045-3051.

16. Rong SB, Hu Y, Enyedy I, Powis G, Meuillet EJ, Wu X, Wang R, Wang S, Kozikowski AP. (2001) Molecular modeling studies of the Akt PH domain and its interaction with phosphoinositides. J Med Chem 44(6):898-908.

17. Wang X, Rahman Z, Sun P, Meuillet E, George D, Bremer EG, Al-Qamari A, Paller AS. (2001) Ganglioside modulates ligand binding to the epidermal growth factor receptor. J Invest Derm 116(1):69-76.

18. Hu Y, Meuillet EJ, Berggren M, Powis G, Kozikowski AP. (2001) 3-Deoxy-3 substituted-D-myo-inositol imidazolyl ether lipid phosphates and carbonate as inhibitors of the phosphatidylinositol 3-kinase pathway and cancer cell growth. Bioorg Med Chem Lett 11(2):173-176.

19. Sun HY, Reddy GB, George C, Meuillet EJ, Berggren M, Powis G, Kozikowski AP. (2002) Synthesis and biological activity of 3-hydroxy(phosphono)methyl-bearing phosphatidylinositol ether lipid analogues. Tetrahedron Lett 43(15):2835-2838.

20. Miljan EA, Meuillet EJ, Mania-Farnell B, George D, Yamamoto H, Simon HG, Bremer EG. (2002) Interaction of the extracellular domain of the epidermal growth factor receptor with gangliosides. J Biol Chem 277(12):10108-10113.

21. Stea B, Falsey R, Kislin K, Patel J, Glanzberg H, Carey S, Ambrad AA, Meuillet EJ, Martinez JD. (2003) Time and dose-dependent radiosensitization of the glioblastoma multiforme U251 cells by the EGF receptor tyrosine kinase inhibitor ZD1839 (‘Iressa’). Cancer Lett 202(1):43-51.

22. Meuillet EJ, Mahadevan D, Vankayalapati H, Berggren M, Williams R, Coon A, Kozikowski AP, Powis G. (2003) Specific inhibition of Akt1 pleckstrin homology domain by D-3-deoxy-phosphatidyl-myo-inositol analogues. Mol Cancer Ther 2(4):389-399.

23. Meuillet EJ, Ihle N, Baker AF, Gard JM, Stamper C, Williams R, Coon A, Mahadevan D, George BL, Kirkpatrick L, Powis G. (2004) In vivo molecular pharmacology and antitumor activity of the targeted Akt inhibitor PX-316. Oncol Res 14(10):513-527.

24. Meuillet E, Stratton S, Cherukuri DP, Goulet AC, Kagey J, Porterfield B, Nelson MA. (2004) Chemoprevention of prostate cancer with selenium: an update on current clinical trials and preclinical findings. J Cell Biochem 91(3):443-458.

25. Meuillet EJ,Mahadevan D, Berggren M, Coon A, Powis G. (2004) Thioredoxin-1 binds to the C2 domain of PTEN inhibiting PTEN’s lipid phosphatase activity and membrane binding: a mechanism for the functional loss of PTEN’s tumor suppressor activity. Arch Biochem Biophys 429(2):123-133.

26. List AF, Glinsmann-Gibson B, Stadheim C, Meuillet EJ, Bellamy W, Powis G. (2004) Vascular endothelial growth factor receptor-1 and receptor-2 initiate a phosphatidylinositide 3-kinase-dependent clonogenic response in acute myeloid leukemia cells. Exp Hematol 32(6):526-535.

27. Jean-Louis S, Akare S, Ali MA, Mash EA Jr., Meuillet E, Martinez JD. (2006) Deoxycholic acid induces intracellular signaling through membrane perturbations. J Biol Chem 281(21):14948-14960.

28. Song Z, Saghafi N, Gokhale V, Brabant M, Meuillet EJ. (2007) Regulation of the activity of the tumor suppressor PTEN by thioredoxin in Drosophila melanogaster. Exp Cell Res 313(6):1161-1171.

29. Cherukuri DP, Chen XB, Goulet AC, Young RN, Han Y, Heimark RL, Regan JW, Meuillet E, Nelson MA. (2007) The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells. Exp Cell Res 313(14):2969-2979.

30. Mahadevan D, Powis G, Mash EA, George B, Gokhale VM, Zhang S, Shakalya K, Du-Cuny L, Berggren M, AliMA, Jana U, Ihle N, Moses S, Franklin C, Narayan S, Shirahatti N, Meuillet EJ. (2008)Discovery of a novel class of AKT pleckstrin homology domain inhibitors. Mol Cancer Ther 7(9):2621-2632.

31. James BP, Staatz WD, Wilkinson ST, Meuillet E, Powis G. (2009) Superoxide dismutase is regulated by LAMMER kinase in Drosophila and human cells. Free Radic Biol Med 46(6):821-827.

32. Berggren M, Sittadjody S, Song Z, Samira JL, Burd R, Meuillet EJ. (2009) Sodium selenite increases the activity of the tumor suppressor protein, PTEN, in DU-125 prostate cancer cells. Nutr Cancer 61(3):322-331.

33. Dexheimer TS, Carey SS, Zuohe S, Gokhale VM, Hu XH, Murata LB, Maes EM, Weichsel A, Sun D, Meuillet EJ, Montfort WR, Hurley LH. (2009) NM23-H2 may play an indirect role in transcriptional activation of c-myc gene expression but does not cleave the nuclease hypersensitive element III1. Mol Cancer Ther 8(5):1363-1377.

34. Moses SA, Ali MA, Zuohe S, Du-Cuny L, Zhou LL, Lemos R, Ihle N, Skillman AG, Zhang S, Mash EA, Powis G, Meuillet EJ. (2009) In vitro and in vivo activity of novel small molecule inhibitors targeting the pleckstrin homology domain of protein kinase B/AKT. Cancer Res 69(12):5073-5081.

35. Block KM, Wang H, Szabó LZ, Polaske NW, Henchey LK, Dubey R, Kushal S, László CF, Makhoul J, Song Z, Meuillet EJ, and Olenyuk BZ. (2009) Direct inhibition of hypoxia-inducible transcription factor complex with designed dimeric epidithiodiketopiperazine. J Amer Chem Soc 131(50):18078-18088.

36. Du-Cuny L, Zuohe S, Moses S, Powis G, Mash EA, Meuillet EJ, Zhang S. (2009) Computational modeling of novel inhibitors targeting the Akt pleckstrin homology domain. Bioorg Med Chem 17(19):6983-6992.

37. Meuillet EJ, Ihle N, Lemos R, Moses SA, Song Z, Zhang S, Mash EA, Powis G (2010). Molecular pharmacology and antitumor activity of PH-427 a novel AKT/PDK1 pleckstrin homology domain inhibitor. Mol Cancer Ther 9(3):706-717.

38. Rosenberg D, Meuillet EJ, Nakanishi M. (2010) Prostaglandin E2 synthase and cancer (2010). A comprehensive invited review, Special Issue in Biochimie “Phospholipase A2 and Lipid Mediators”. 92(6):660-664.

39. Du-Cuny L, Morrow JK, Chen L, Meuillet EJ, Powis G, Mash EA, Zhang S (2011). Recent development of anticancer therapeutics targeting the Akt pathway. Recent Patents on Anti-cancer Drug Discovery. 6(1):146-59.

40. Ali MA, Zhou LL, Moses S, Zuohe S, Ghosh SC, Du-Cuny L, Lemos R, Ihle N, Zhang S, Powis G, Meuillet EJ, Mash EA. (2011) Development of sulfonamide Akt PH domain inhibitors. Bioorg. Med. Chem 19(6):2046-54

41. Meuillet, EJ. (2011) Novel Inhibitors of AKT: Assessment of a Different Approach Targeting the Pleckstrin Homology Domain. Current Medicinal Chemistry 18(18):2727-42.

42. Chang HH, Song Z, Wisner L, Tripp T, Gokhale V, Meuillet EJ. (2011) Identification of a novel class of mPGES-1 inhibitor with anti-tumor activity in colorectal and lung cancer models. Invest. New Drugs. http://www.ncbi.nlm.nih.gov/pubmed/21931968

43. Chang HH, and Meuillet EJ. (2011) Identification and development of mPGES-1 inhibitors: Where we are at? Fut. Med. Chem. 3(15):1909-34.

44. Smith B, Chang HH, Medda F, Gokhale V, Dietrich J, Davis A, Meuillet EJ, Hulme C. (2012) Synthesis and Biological Activity of 2-Aminothiazoles as Novel Inhibitors of PGE2 Production in Cells. Bioorg. Med. Chem. Let. 22(10):3567-70.

45. Jandova J, Beyer TE, Meuillet EJ and Watts GS (2012). The matrix protein CCN1/CYR61 is required for αVβ5-mediated cancer cell migration. Cell Biochem. Funct. 30(8):687-95.

46. Stephen RM, Baker A, Brown K, Meuillet EJ, Gillies B. (2012). Tumorigenicity, pAkt and diffusion MRI in early passage breast cancer cell lines. Exp. Biol. Med. 237(11):1273-80. Featured Article

47. Medda F, Sells E, Chang HH, Dietrich J, Chappeta S, Smith B, Gokhale V, Meuillet EJ and Hulme C. (2013) Synthesis and biological activity of aminophthalazines and aminopyridazines as novel inhibitors of PGE2 production in cells. Bioorg. Med. Chem. Let. 23(2):528-231.

48. Sells E, Norberg J and Meuillet EJ. (2013) Targeting mPGES-1 for inflammatory-related diseases: a novel way to regulate PGE2? Pharmaceutical Patent Analyst, 2(2):265-288.

49. Cantoria M, Lugunero T, Boros LG and Meuillet EJ. (2013) Contextual Synthetic Inhibition of Fatty Acid Synthesis by Metformin Involves Glucose-derived Acetyl-CoA, K-ras and Cholesterol in Pancreatic Tumor Cells. Metabolomics (open access) DOI 10.1007/s11306-013-0555-4.

50. Lucero-Acuna A, Moses SA, Jeffrey J, Abril ER, Nagle R, Guzman R, Pagel MD, and Meuillet EJ (2014) Nanoparticles delivery of a novel AKT/PDK1 inhibitor inhibits pancreatic cancer tumor growth and metastasis. Int. J. Nanomed. (In press).

51. Cantoria MJ, Patel H, Boros LG and Meuillet EJ (2014) Metformin and Pancreatic Cancer Metabolism. In Pancreatic Cancer – Insights into molecular mechanisms and novel approaches to early detection and treatment” Edited by Kelly McCall, ISBN 978-953-51-1375-1, InTech, DOI: 10.5772/57432, Chapter 7.

52. Boros LG, Beger RD, Somlyai G, Colca JR, Szalma S, Thompson PA and Meuillet EJ (2014). Targeted tracer fate associations in drug efficacy testing in cancer. In Tumor Cell Metabolism – Pathways, Regulation and Biology, Sybille Mazurek and Maria Shoshan (Eds.); Springer-Verlag Gmbh, Heidelberg, Germany, European Union. pp349-371

53. Chen L, Du-Cuny L, Moses S, Dumas S, Song Z, Meuillet EJ, Zhang S. In silico discovery and experimental evaluation of small-molecule inhibitors targeting GAB1 pleckstrin homology domain. Phos Computational Biology (In press).

Professional Information
Professional Affiliations: 
Local/State Outreach:
 
2008 – present: Research Corporation for Science Advancement Arizona Partners in Science Program, Member
2008 – present: Arizona Science Teacher Advancement and Research Training (AZ-START) Program, Mentor
2007 – present: Arizona Bioindustry Association (AZBio) / Bioindustry Organization of Southern Arizona (BIO-SA), Member
 
National/International Outreach:
 
2011 – present: Journal of Investigative Dermatology, Ad hoc Reviewer
2011 – present: American Heart Association, Scientist Reviewer
2008 – present: Molecular Cancer Therapeutics, Ad hoc Reviewer
2008 – present: Cancer Research, Ad hoc Reviewer
2008 – present: Carcinogenesis, Ad hoc Reviewer
2008 – present: Journal of Nutrition, Ad hoc Reviewer
2006 – present: More Graduate Education @ Mountain States Alliance (MGE@MSA), Member
2005 – present: Department of Defense, Breast Cancer Research Program, Cell Biology 3 Panel, Scientist Reviewer
2005 – present: Department of Defense, Prostate Cancer Research Program, Scientist Reviewer
2004 – present: American Society of Nutritional Sciences, Member
2004 – present: European Association for Cancer Research, Member
1999 – present: American Association for Cancer Research, Member
2004 – 2006: American Diabetes Association, Member
1996 – 1998: Association Française Retinitis Pigmentosa (AFRP), Member
1995 – 1996: Neuroscience Society, Member
 
Nutritional Sciences Departmental Committees:
 
2009 – 2010: Nutritional Sciences Graduate Program Executive Committee, Member
2006 – 2009: Nutritional Sciences Journal Club, Organizer and Chair
2004 – 2008: Nutritional Sciences Post-Tenure/Peer Review Committee, Member
2004 – 2007: Research Frontiers in Nutritional Sciences Organizing Committee, Member
2004 – 2006: Nutritional Sciences Undergraduate Curriculum Committee, Member
 
University Committees:
 
2011 – present: Minority Access to Research Careers (MARC) Program, Internal Advisory Committee
2010 – present: Keep Engaging Youth in Science (KEYS) Research Internship Program, Member
2007 – present: Minority Health Disparities Summer Research Program (MHD/SROP), Member
2007 – present: Minority Access to Research Careers (MARC) Program, Member
2006 – present: Drug Development and Experimental Therapeutics Program, Member
2004 – present: BIO5 Institute for Collaborative Research, Member
2004 – present: Cancer Biology Interdisciplinary Graduate Program, Advisor
2002 – present: Arizona Cancer Center, Member
2001 – present: Cancer Biology and Genetic Program, Member
2004 – 2007: American Cancer Society / Arizona Cancer Center Institutional Review Group, Scientist Reviewer
2002 – 2004: Medical Student Research Program (MSRP), Mentor
Honors: 

2008: Mortar Board Senior Honor Society Award
2007: Fellowship, Wakonse Conference on College Teaching, Wakonse Foundation
2007: Honorable Mention, The Nancy R. Gelman Foundation, New York, NY
2000 – 2003: Postdoctoral Fellowship, National Institutes of Health, National Cancer Institute
1997 – 1999: Postdoctoral Award, The Gus Foundation, Chicago, IL
1997: Travel Award, National Science Foundation (for Glyco XIV, Zurich)
1995 – 1996: Postdoctoral Award, Association Française Retinitis Pigmentosa (AFRP), Colomiers, France
1995: Postdoctoral Travel Award, Medical Research Foundation (France)
1993 – 1995: PhD Fellowship, French Government (Ministère de Recherche et Technologie, MRT)
1992 – 1993: DEA Fellowship, French Government