Anne-Laure Mahul Mellier
Publications
1. Levine, P.M., Galesic, A., Balana, A.T., Mahul-Mellier, A.L., Navarro, M.X., De Leon, C.A., Lashuel, H.A., and Pratt, M.R. (2019). alpha-Synuclein O-GlcNAcylation alters aggregation and toxicity, revealing certain residues as potential inhibitors of Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America 116, 1511-1519. 2. Desclous A., GruBmayer KS., Bostan E, Lukes T., Bouwens A., Sharipov A., Geissbuehler S, Mahul-Mellier AL., Lashuel HA, Leutenegger M., Lasser T. Combined Multi-Plane Tomographic Phase Retrieval and S tochastic Optical Fluctuation Imaging for 4D Cell Microscopy. Nature Photonics. 2018, 12, 165–172. 3. Ait-Bouziad, N., Lv, G., Mahul-Mellier, A.L., Xiao, S., Zorludemir, G., Eliezer, D., Walz, T., and Lashuel, H.A. (2017). Discovery and characterization of stable and toxic Tau/phospholipid oligomeric complexes. Nature communications 8, 1678. 4. Ruggeri, F.S., Mahul-Mellier, A.L., Kasas, S., Lashuel, H.A., Longo, G., and Dietler, G. (2017). Amyloid single-cell cytotoxicity assays by nanomotion detection. Cell death discovery 3, 17053. 5. Alzoubi, S., Brody, L., Rahman, S., Mahul-Mellier, A.L., Mercado, N., Ito, K., El-Bahrawy, M., Silver, A., Boobis, A., Bell, J.D., and Hajji, N. (2016). Synergy between histone deacetylase inhibitors and DNA-damaging agents is mediated by histone deacetylase 2 in colorectal cancer. Oncotarget 7, 44505-44521. 6. Benmessaoud, I.R., Mahul-Mellier, A.L., Horvath, E., Maco, B., Spina, M., Lashuel, H.A., and Forro, L. (2016). Health hazards of methylammonium lead iodide based perovskites: cytotoxicity studies. Toxicology research 5, 407-419. 7. Dikiy, I., Fauvet, B., Jovicic, A., Mahul-Mellier, A.L., Desobry, C., El-Turk, F., Gitler, A.D., Lashuel, H.A., and Eliezer, D. (2016). Semisynthetic and in Vitro Phosphorylation of Alpha-Synuclein at Y39 Promotes Functional Partly Helical Membrane-Bound States Resembling Those Induced by PD Mutations. ACS chemical biology 11, 2428-2437. 8. Mahul-Mellier, A.L., Vercruysse, F., Maco, B., Ait-Bouziad, N., De Roo, M., Muller, D., and Lashuel, H.A. (2015). Fibril growth and seeding capacity play key roles in alpha-synuclein-mediated apoptotic cell death. Cell death and differentiation 22, 2107-2122. 9. Mahul-Mellier, A.L., Fauvet, B., Gysbers, A., Dikiy, I., Oueslati, A., Georgeon, S., Lamontanara, A.J., Bisquertt, A., Eliezer, D., Masliah, E., et al. (2014). c-Abl phosphorylates alpha-synuclein and regulates its degradation: implication for alpha-synuclein clearance and contribution to the pathogenesis of Parkinson's disease. Human molecular genetics 23, 2858-2879. 10. Khalaf, O., Fauvet, B., Oueslati, A., Dikiy, I., Mahul-Mellier, A.L., Ruggeri, F.S., Mbefo, M.K., Vercruysse, F., Dietler, G., Lee, S.J., et al. (2014). The H50Q mutation enhances alpha-synuclein aggregation, secretion, and toxicity. The Journal of biological chemistry 289, 21856-21876. 11. Pazarentzos, E., Mahul-Mellier, A.L., Datler, C., Chaisaklert, W., Hwang, M.S., Kroon, J., Qize, D., Osborne, F., Al-Rubaish, A., Al-Ali, A., et al. (2014). IkappaBetaalpha inhibits apoptosis at the outer mitochondrial membrane independently of NF-kappaB retention. The EMBO journal 33, 2814-2828. 12. Datler, C., Pazarentzos, E., Mahul-Mellier, A.L., Chaisaklert, W., Hwang, M.S., Osborne, F., and Grimm, S. (2014). CKMT1 regulates the mitochondrial permeability transition pore in a process that provides evidence for alternative forms of the complex. Journal of cell science 127, 1816-1828. 13. Mahul-Mellier, A.L., Datler, C., Pazarentzos, E., Lin, B., Chaisaklert, W., Abuali, G., and Grimm, S. (2012). De-ubiquitinating proteases USP2a and USP2c cause apoptosis by stabilising RIP1. Biochimica et biophysica acta 1823, 1353-1365. 14. Mahul-Mellier, A.L., Pazarentzos, E., Datler, C., Iwasawa, R., AbuAli, G., Lin, B., and Grimm, S. (2012). De-ubiquitinating protease USP2a targets RIP1 and TRAF2 to mediate cell death by TNF. Cell death and differentiation 19, 891-899. 15. Iwasawa, R., Mahul-Mellier, A.L., Datler, C., Pazarentzos, E., and Grimm, S. (2011). Fis1 and Bap31 bridge the mitochondria-ER interface to establish a platform for apoptosis induction. The EMBO journal 30, 556-568. 16. Lemarie, A., Huc, L., Pazarentzos, E., Mahul-Mellier, A.L., and Grimm, S. (2011). Specific disintegration of complex II succinate:ubiquinone oxidoreductase links pH changes to oxidative stress for apoptosis induction. Cell death and differentiation 18, 338-349. 17. Irshad, S., Mahul-Mellier, A.L., Kassouf, N., Lemarie, A., and Grimm, S. (2009). Isolation of ORCTL3 in a novel genetic screen for tumor-specific apoptosis inducers. Cell death and differentiation 16, 890-898. 18. Mahul-Mellier, A.L., Strappazzon, F., Chatellard-Causse, C., Blot, B., Beal, D., Torch, S., Hemming, F., Petiot, A., Verna, J.M., Fraboulet, S., and Sadoul, R. (2009). Alix and ALG-2 make a link between endosomes and neuronal death. Biochemical Society transactions 37, 200-203. 19. Mahul-Mellier, A.L., Strappazzon, F., Petiot, A., Chatellard-Causse, C., Torch, S., Blot, B., Freeman, K., Kuhn, L., Garin, J., Verna, J.M., et al. (2008). Alix and ALG-2 are involved in tumor necrosis factor receptor 1-induced cell death. The Journal of biological chemistry 283, 34954-34965. 20. Mahul-Mellier, A.L., Hemming, F.J., Blot, B., Fraboulet, S., and Sadoul, R. (2006). Alix, making a link between apoptosis-linked gene-2, the endosomal sorting complexes required for transport, and neuronal death in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience 26, 542-549. 21. Fraboulet, S., Hemming, F.J., Mahul, A.L., Cristina, N., and Sadoul, R. (2003). Expression of Alix protein during early avian development. Gene expression patterns : GEP 3, 139-142.
EPFL SV BMI LMNN
AI 2149 (Bâtiment AI)
Station 19
1015 Lausanne
Web site: Web site: https://lashuel-lab.epfl.ch/
+41 21 693 61 63
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+41 21 693 61 63
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SSV-ENS
Web site: Web site: https://sv.epfl.ch/education
Fields of expertise
Developmental Biology: electroporation in vivo in chick embryo, handling and staging of early chick embryo, cryostat sectioning, histology, TUNEL staining, immunohistochemistry.
Molecular Biology:
Plasmid construction, site-directed mutagenesis (deletion, insertion, point mutation), TOPo-cloning; Gateway cloning; PCR, RT-PCR, Q-RT-PCR
Biochemical Biology:
Western Blot, bringing to light evidence of protein interactions through immunoprecipitation, ubiquitination/deubiquitination assay in vivo and in vitro, Kinase assay.
Cellular Biology:
cell culture, neuronal primary culture, transfection, siRNA, shRNA, stable clone, immunocytochemistry, immunofluorescence, confocal microscopy, flow cytometry, lentivirus production and infection.
Quantification of cell Death: TUNEL, Hoechst, Propidium iodide (PI), 3,3?-dihexyloxacarbocyanine iodide (DIOC), caspase activity and MTT-test.
Academic Degrees
2007: PhD in Neurobiology - University Joseph Fourier- Grenoble Alix, a link between cell death and the endolysosomal pathway Board of examiners : Pr Nonchev, Dr Mehlen, Dr Micheau, Dr Haase and Dr Aubry 2003: Masters degree in Molecular and Cellular Biology - University Joseph Fourier- Grenoble 2002: Masters degree in Cell Biology and Physiology - University Joseph Fourier- Grenoble 2001: Bachelors degree in Cell Biology and Physiology - University Joseph Fourier- Grenoble 2000: General Biology Studies - University Jean Monnet Saint Etienne 1997-1999: Faculty of Medicine - University Jean Monnet Saint EtienneResearch Experiences
2012-present: Laboratory of Molecular and Chemical Biology of Neurodegeneration, PI : Prof Hilal Lashuel-EPFL-Lausanne. Research Associate. Research Topic : Role of post-transalational modification on a-synuclein regulation Co-supervisor of 2 PhD students. 2007-2011 : Apoptosis Research Group, PI: Pr. Stefan Grimm Imperial College- London Research associate. Research topic: The deubiquitinating enzyme USP2 decides about cell death of breast cancer cells. Grant: BCC (Breast Cancer Campaign) for 3 years. Co-supervisor of 2 PhD students. GM adviser for the Experimental Medicine and Toxicology department, Imperial College. 2002-2007: Laboratory Neurodégénérescence et Plasticité, PI: Pr. Rémy Sadoul - UJF - Grenoble PhD and Master training period. Head of research: Dr. Sandrine Fraboulet. Research topic: Alix, a link between neuronal death and the endosomal sorting complexes required for transport, in vivo. Grant : MNRT (Ministère nationale de la recherche et des technologies). Teaching (64 hours/year) Level 1 for the practice and ethics animal experimentation 2001-2002 (3 months) Laboratory Neurodégénérescence et Plasticité, PI: Pr. Rémy Sadoul - UJF - Grenoble Lab work for the master degree. Head of research: Dr. Sandrine Fraboulet. Research topic: Overexpression of Alix protein, in vivo, in neural tube of chick embryo. 2001 (6 weeks) Laboratory Neurodégénérescence et Plasticité, PI: Pr. Rémy Sadoul - UJF - Grenoble Lab work for the Bachelors degree. Head of research: Dr. Sandrine Fraboulet Research topic: Expression of Alix protein during early avian development.Research Results
I have completed my PhD in Neurobiology in 2007, with underlining the role, in vivo, of Alix and the proteins found in the ESCRT (Endosomal Sorting Complex Required for Transport) complex in the programmed cell death of motor neurons during embryonic development of the chicken. I have furthermore been able to show the role, in vivo, of the TNFR1 (Tumor Necrosis Factor Receptor 1) at the time of death of these motor neurons. I subsequently developed a model of cell death, in vitro, in HEK (Human Embryonic Kidney) cells to determine whether Alix plays a role in the death signalling pathway of TNFR1. At the end of my PhD, I have joined the Apoptosis group leads by Pr Stefan Grimm at Imperial College and worked during 3 years on the role of USP2, a deubiquitinating protease, in the decision-making between cell death and survival in the TNF? depending signalling pathway in breast cancer cell line MCF7. I have furthermore been able to show that USP2 interacts in a complex with TRAF2 and RIP1 and regulates the ubiquitination state of RIP1 leading to trigger apoptosis via the caspase 8 activation. Moreover, the anti-apoptotic TRAF2 might be a counter-player of pro-apoptotic USP2. Our experiments suggest that the ratio between USP2 and TRAF2 protein level that confers the sensitivity of MCF7 to cell death or cell survival.Scientific Communcation
Poster Presentation : Iwasawa R, Mahul-Mellier AL, Datler C and Grimm S. Fission protein Fis1 and Bap31 bridge the mitochondria/ER interface to establish a platform for apoptosis induction. Cell Death, Gordon Research Conference, Newport, 2010. Mahul-Mellier AL, Datler C, Pazarentzos E, Grimm S. The deubiquitinating enzyme USP2 decides between cell death and survival in the TNFalpha depending signalling pathway. European Cell Death Organisation (ECDO), Paris, 2009. ECDOs scholarship. Iwasawa R, Mahul-Mellier AL, Datler C and Grimm S. Fission protein Fis1 and Bap31 bridge the mitochondria/ER interface to establish a platform for apoptosis induction. European Cell Death Organisation (ECDO), Paris, 2009. Mahul-Mellier AL, Strappazzon F, Petiot A, Chatellard-Causse C, Torch S, Blot B, Freeman K, Kuhn L, Garin J, Verna JM, Fraboulet S, Sadoul R. Alix and ALG-2 are involved in TNF-R1 induced cell death. ESCRTs - from cell biology to pathogenesis, Cambridge, 2008. Mahul AL, Hemming F, Sadoul R and Fraboulet S. A molecular link between neuronal death and the endo-lysosomal system. Forum of European Neurosciences (FENS), Lisbon, 2004. French Society of Neurosciences s scholarship. Oral communication : The deubiquitinating enzyme USP2 decides between cell death and survival in the TNF? signaling pathway. Grenoble Institute of Neurosciences, Grenoble, 2010. The deubiquitinating enzyme USP2 decides about the cell death of breast cancer cells. Breast Cancer Campaign Conference, London, 2008. Alix/ALG-2, a link between cell death and endolysosomal system. The Institute of Cancer Research, Dr Pascal Meiers lab, London, 2007. Alix/ALG-2 making a link between endosomes and death signaling in vivo. 36th Annual Meeting of Neuroscience (SfN), Atlanta, 2006. Alix, a link between the endolysosomal system and neuronal cell death in vivo. Laboratory Motor Neuron development and Pathology, Columbia University, New York, 2006. Alix is involved in the programmed cell death of cervical motoneurons in the chick embryo. PhD student's day, UJF, Grenoble, 2005.Publications
Other publications
Publications
1. Levine, P.M., Galesic, A., Balana, A.T., Mahul-Mellier, A.L., Navarro, M.X., De Leon, C.A., Lashuel, H.A., and Pratt, M.R. (2019). alpha-Synuclein O-GlcNAcylation alters aggregation and toxicity, revealing certain residues as potential inhibitors of Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America 116, 1511-1519. 2. Desclous A., GruBmayer KS., Bostan E, Lukes T., Bouwens A., Sharipov A., Geissbuehler S, Mahul-Mellier AL., Lashuel HA, Leutenegger M., Lasser T. Combined Multi-Plane Tomographic Phase Retrieval and S tochastic Optical Fluctuation Imaging for 4D Cell Microscopy. Nature Photonics. 2018, 12, 165–172. 3. Ait-Bouziad, N., Lv, G., Mahul-Mellier, A.L., Xiao, S., Zorludemir, G., Eliezer, D., Walz, T., and Lashuel, H.A. (2017). Discovery and characterization of stable and toxic Tau/phospholipid oligomeric complexes. Nature communications 8, 1678. 4. Ruggeri, F.S., Mahul-Mellier, A.L., Kasas, S., Lashuel, H.A., Longo, G., and Dietler, G. (2017). Amyloid single-cell cytotoxicity assays by nanomotion detection. Cell death discovery 3, 17053. 5. Alzoubi, S., Brody, L., Rahman, S., Mahul-Mellier, A.L., Mercado, N., Ito, K., El-Bahrawy, M., Silver, A., Boobis, A., Bell, J.D., and Hajji, N. (2016). Synergy between histone deacetylase inhibitors and DNA-damaging agents is mediated by histone deacetylase 2 in colorectal cancer. Oncotarget 7, 44505-44521. 6. Benmessaoud, I.R., Mahul-Mellier, A.L., Horvath, E., Maco, B., Spina, M., Lashuel, H.A., and Forro, L. (2016). Health hazards of methylammonium lead iodide based perovskites: cytotoxicity studies. Toxicology research 5, 407-419. 7. Dikiy, I., Fauvet, B., Jovicic, A., Mahul-Mellier, A.L., Desobry, C., El-Turk, F., Gitler, A.D., Lashuel, H.A., and Eliezer, D. (2016). Semisynthetic and in Vitro Phosphorylation of Alpha-Synuclein at Y39 Promotes Functional Partly Helical Membrane-Bound States Resembling Those Induced by PD Mutations. ACS chemical biology 11, 2428-2437. 8. Mahul-Mellier, A.L., Vercruysse, F., Maco, B., Ait-Bouziad, N., De Roo, M., Muller, D., and Lashuel, H.A. (2015). Fibril growth and seeding capacity play key roles in alpha-synuclein-mediated apoptotic cell death. Cell death and differentiation 22, 2107-2122. 9. Mahul-Mellier, A.L., Fauvet, B., Gysbers, A., Dikiy, I., Oueslati, A., Georgeon, S., Lamontanara, A.J., Bisquertt, A., Eliezer, D., Masliah, E., et al. (2014). c-Abl phosphorylates alpha-synuclein and regulates its degradation: implication for alpha-synuclein clearance and contribution to the pathogenesis of Parkinson's disease. Human molecular genetics 23, 2858-2879. 10. Khalaf, O., Fauvet, B., Oueslati, A., Dikiy, I., Mahul-Mellier, A.L., Ruggeri, F.S., Mbefo, M.K., Vercruysse, F., Dietler, G., Lee, S.J., et al. (2014). The H50Q mutation enhances alpha-synuclein aggregation, secretion, and toxicity. The Journal of biological chemistry 289, 21856-21876. 11. Pazarentzos, E., Mahul-Mellier, A.L., Datler, C., Chaisaklert, W., Hwang, M.S., Kroon, J., Qize, D., Osborne, F., Al-Rubaish, A., Al-Ali, A., et al. (2014). IkappaBetaalpha inhibits apoptosis at the outer mitochondrial membrane independently of NF-kappaB retention. The EMBO journal 33, 2814-2828. 12. Datler, C., Pazarentzos, E., Mahul-Mellier, A.L., Chaisaklert, W., Hwang, M.S., Osborne, F., and Grimm, S. (2014). CKMT1 regulates the mitochondrial permeability transition pore in a process that provides evidence for alternative forms of the complex. Journal of cell science 127, 1816-1828. 13. Mahul-Mellier, A.L., Datler, C., Pazarentzos, E., Lin, B., Chaisaklert, W., Abuali, G., and Grimm, S. (2012). De-ubiquitinating proteases USP2a and USP2c cause apoptosis by stabilising RIP1. Biochimica et biophysica acta 1823, 1353-1365. 14. Mahul-Mellier, A.L., Pazarentzos, E., Datler, C., Iwasawa, R., AbuAli, G., Lin, B., and Grimm, S. (2012). De-ubiquitinating protease USP2a targets RIP1 and TRAF2 to mediate cell death by TNF. Cell death and differentiation 19, 891-899. 15. Iwasawa, R., Mahul-Mellier, A.L., Datler, C., Pazarentzos, E., and Grimm, S. (2011). Fis1 and Bap31 bridge the mitochondria-ER interface to establish a platform for apoptosis induction. The EMBO journal 30, 556-568. 16. Lemarie, A., Huc, L., Pazarentzos, E., Mahul-Mellier, A.L., and Grimm, S. (2011). Specific disintegration of complex II succinate:ubiquinone oxidoreductase links pH changes to oxidative stress for apoptosis induction. Cell death and differentiation 18, 338-349. 17. Irshad, S., Mahul-Mellier, A.L., Kassouf, N., Lemarie, A., and Grimm, S. (2009). Isolation of ORCTL3 in a novel genetic screen for tumor-specific apoptosis inducers. Cell death and differentiation 16, 890-898. 18. Mahul-Mellier, A.L., Strappazzon, F., Chatellard-Causse, C., Blot, B., Beal, D., Torch, S., Hemming, F., Petiot, A., Verna, J.M., Fraboulet, S., and Sadoul, R. (2009). Alix and ALG-2 make a link between endosomes and neuronal death. Biochemical Society transactions 37, 200-203. 19. Mahul-Mellier, A.L., Strappazzon, F., Petiot, A., Chatellard-Causse, C., Torch, S., Blot, B., Freeman, K., Kuhn, L., Garin, J., Verna, J.M., et al. (2008). Alix and ALG-2 are involved in tumor necrosis factor receptor 1-induced cell death. The Journal of biological chemistry 283, 34954-34965. 20. Mahul-Mellier, A.L., Hemming, F.J., Blot, B., Fraboulet, S., and Sadoul, R. (2006). Alix, making a link between apoptosis-linked gene-2, the endosomal sorting complexes required for transport, and neuronal death in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience 26, 542-549. 21. Fraboulet, S., Hemming, F.J., Mahul, A.L., Cristina, N., and Sadoul, R. (2003). Expression of Alix protein during early avian development. Gene expression patterns : GEP 3, 139-142.Teaching & PhD
Teaching
Life Sciences Engineering