Metabolic and neurodegenerative diseases
Dr. Ana Messias
About us
Messias' research focuses on basic molecular mechanisms in several human metabolic and neurodegenerative diseases. In particular, we are interested in how proteins perform their native functions and how diseases alter them. We do this by looking at the details of their 3D structure in an integrative structural biology approach combined with biochemical and biophysical techniques. This information is then used in the rational development of novel drugs to ameliorate disease conditions.
Current research centers around rare inherited disorders such as Neurodegenerative With Brain Iron Accumulation (NBIA) and Dilated Cardiomyopathy. Among NBIA diseases, we study MPAN (Mitochondrial-Membrane Protein-Associated Neurodegeneration), a fatal disease caused by mutations in C19orf12, a protein with no known biological function. The aim of our research is to understand the basic molecular and cellular mechanisms of C19orf12 and how mutations lead to MPAN by using structural biology, biochemistry, biophysics, combined with proteomics, and cellular biology. Our ultimate goal is to develop personalized drugs that will prolong and improve the lives of MPAN patients.
A second research area focuses on genetic and acquired metabolic diseases, in particular linked to diabetes and obesity. We unravel and exploit novel molecular features of the function of regulatory proteins in insulin- and leptin-based signalling, namely of protein tyrosine phosphatases (PTPs), and use it in structure-based drug discovery to identify and develop novel allosteric compounds in diabetes and obesity.
Publications
Zhang, F. ; Dorn, T. ; Gnutti, B. ; Anikster, Y. ; Kuebler, S. ; Ahrens-Nicklas, R. ; Gosselin, R. ; Rahman, S. ; Durst, R. ; Zanuttigh, E. ; Güra, M. ; Poch, C.M. ; Meier, A.B. ; Laugwitz, K.L. ; Schüller, H.J. ; Messias, A.C. ; Sibon, O.C. ; Finazzi, D. ; Rippert, A.L. ; Li, D. ; Truxal, K. ; Nandi, D. ; Lampert, B.C. ; Yeo, M. ; Gardham, A. ; Nissan, B. ; Horowitz Cederboim, S. ; Moretti, A. ; Iuso, A.
Pantethine ameliorates dilated cardiomyopathy features in PPCS deficiency disorder in patients and cell line models.Klingelhuber, F. ; Frendo-Cumbo, S. ; Omar-Hmeadi, M. ; Massier, L. ; Kakimoto, P. ; Taylor, A.J. ; Couchet, M. ; Ribicic, S. ; Wabitsch, M. ; Messias, A.C. ; Iuso, A. ; Müller, T.D. ; Rydén, M. ; Mejhert, N. ; Krahmer, N.
A spatiotemporal proteomic map of human adipogenesis.Zanuttigh, E. ; Derderian, K. ; Güra, M. ; Geerlof, A. ; Di Meo, I. ; Cavestro, C. ; Hempfling, S. ; Ortiz Collazos, S. ; Mauthe, M. ; Kmiec, T. ; Cammarota, E. ; Panzeri, M.C. ; Klopstock, T. ; Sattler, M. ; Winkelmann, J. ; Messias, A.C. ; Iuso, A.
Identification of autophagy as a functional target suitable for the pharmacological treatment of mitochondrial membrane protein-associated neurodegeneration (MPAN) in vitro.Chora, A.F. ; Pedroso, D. ; Kyriakou, E. ; Pejanovic, N. ; Colaço, H. ; Gozzelino, R. ; Barros, A. ; Willmann, K. ; Velho, T.R. ; Moita, C. ; Santos, I. ; Pereira, P. ; Carvalho, S. ; Martins, F.B. ; Ferreira, J.A. ; de Almeida, S.F. ; Benes, V. ; Anrather, J. ; Weis, S. ; Soares, M.P. ; Geerlof, A. ; Neefjes, J.J. ; Sattler, M. ; Messias, A.C. ; Neves Costa, A. ; Moita, L.F.
DNA damage independent inhibition of NF-kB transcription by anthracyclines.Niu, Z. ; Prade, E. ; Malideli, E. ; Hille, K. ; Jussupow, A. ; Mideksa, Y.G. ; Yan, L.M. ; Qian, C. ; Fleisch, M. ; Messias, A.C. ; Sarkar, R. ; Sattler, M. ; Lamb, D.C. ; Feige, M.J. ; Camilloni, C. ; Kapurniotu, A. ; Reif, B.
Structural insight into IAPP-derived amyloid inhibitors and their mechanism of action.Jussupow, A. ; Messias, A.C. ; Stehle, R. ; Geerlof, A. ; Solbak, S.M.Ø. ; Paissoni, C. ; Bach, A. ; Sattler, M. ; Camilloni, C.
The dynamics of linear polyubiquitin.de Angelis, M. ; Schriever, S.C. ; Kyriakou, E. ; Sattler, M. ; Messias, A.C. ; Schramm, K.-W. ; Pfluger, P.T.
Detection and quantification of the anti-obesity drug celastrol in murine liver and brain.Niu, Z. ; Prade, E. ; Malideli, E. ; Hille, K. ; Jussupow, A. ; Mideksa, Y.G. ; Yan, L.M. ; Qian, C. ; Fleisch, M. ; Messias, A.C. ; Sarkar, R. ; Sattler, M. ; Lamb, D.C. ; Feige, M.J. ; Camilloni, C. ; Kapurniotu, A. ; Reif, B.
Structural insight into IAPP-derived amyloid inhibitors and their mechanism of action.Ostertag, M.S. ; Messias, A.C. ; Sattler, M. ; Popowicz, G.M.
The structure of the SPOP-Pdx1 interface reveals insights into the phosphorylation-dependent binding regulation.Harrison, L. ; Schriever, S.C. ; Feuchtinger, A. ; Kyriakou, E. ; Baumann, P. ; Pfuhlmann, K. ; Messias, A.C. ; Walch, A.K. ; Tschöp, M.H. ; Pfluger, P.T.
Fluorescent blood-brain barrier tracing shows intact leptin transport in obese mice.Previous and Current Funding
Michael J. Fox Foundation (US), NBIA-DA (US), Association NBIA Poland (Poland)
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