Óscar Millet
omillet
Óscar Millet
PRINCIPAL INVESTIGATOR
Precision Medicine and Metabolism Lab
Address: Bizkaia Science and Technology Park, building 800, Derio (Bizkaia)

He holds degrees in Chemistry (Univ. Ramon Llull,1994) and Chemical Engineering (IQS, 1995). After obtaining a Ph D in Organic Chemistry (University of Barcelona, 1999) he joined the group of Lewis Kay in Toronto for a post-doctoral stay (University of Toronto, 2000-2004). He was then recipient of a Ramon y Cajal reincorporation contract at the Parc Cientific de Barcelona (2004-2006) and he currently is group leader at the CIC bioGUNE. His research line focuses of the use of nuclear magnetic resonance (NMR) to the study of biologically relevant proteins and enzymes, paying special attention to the delicate balance existing between protein stability and dynamics. Such knowledge is applied for the development of new compounds with therapeutic activity, specifically in the field of rare diseases. He have published more than 55 papers with a total number of citations (1998-2015) of 2050 and an h-index of 17. He was the Spanish delegate for the trans domain of the COST program (2009-2014). He was awarded the prize of the Real Sociedad Española de Química (2004) and the Spanish NMR group prize (2005). He currently is the president of the Spanish NMR group.

Latest Publications

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Protein stability (thermodynamic and kinetic) drives the biophysical properties of the polypeptide chain (protein folding) and the protein's concentration in the cellular environment (protein homeostasis). It is the result of a delicate balance between inter- and intramolecular interactions, which can be easily altered by mutations and/or upon changes in the composition of the surrounding media. In this context, NMR spectroscopy offers a plethora of suitable experiments to investigate protein stability. In our laboratory we are currently interested in the following topics:

  • Pharmacological chaperones. Rare diseases (~7000 identified to date) are an area of significant medical need affecting an estimated 350 million people worldwide, with ~95% having no currently approved drug treatment. They are often produced by inherited mutations affecting the activity of a protein and It is becoming increasily clear that, most frequently, a mutation destabilizes the protein/enzyme, ultimately affecting its intracellular homeostasis. In this context, pharmacological chaperones (small molecules which bind to the protein, restoring stability and activity without affecting its function) can be applied to many diseases. In our laboratory we are investigating new methods (NMR, biophysical and biochemical) for the discovery and characterization of pharmacological chaperones against a set of diseases: congenital eryhtropoietic porphyria, tyrosianemia.
     
  • Environmental modulation of enzyme stability. The high catalytic efficiency and the exquisite enantioselectivity of an enzyme has been employed in some industrial processes to upgrade their properties in order to make them more environmentally-friendly. However, large scale industrial implementation of biotechnological reactions is often limited by the marginal stability of the enzyme in the reactor conditions. In our laboratory we employ NMR and circular dichroism to investigate the effect of external crowding agents to improve the activity and stability of several enzymes. Specifically, we are investigating the mechanism for protein haloadaptation by a combined use of site directed mutagenesis and high-resolution NMR spectroscopy.

Protocolos de Histología

Latest Publications

The L-alpha-Lysophosphatidylinositol/G Protein-Coupled Receptor 55 System Induces the Development of Nonalcoholic Steatosis and Steatohepatitis

Fondevila, MF;Fernandez, U;Gonzalez-Rellan, MJ;Lima, ND;Buque, X;Gonzalez-Rodriguez, A;Alonso, C;Iruarrizaga-Lejarreta, M;Delgado, TC;Varela-Rey, M;Senra, A;Garcia-Outeiral, V;Novoa, E;Iglesias, ...

HEPATOLOGY

2020-11-13

S-adenosyl-L-methionine (SAMe) halts the autoimmune response in patients with primary biliary cholangitis (PBC) via antioxidant and S-glutathionylation processes in cholangiocytes

Kilanczyk, E;Banales, JM;Wunsch, E;Barbier, O;Avila, MA;Mato, JM;Milkiewicz, M;Milkiewicz, P

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

2020-11-01

Lysine and Arginine Protein Post-translational Modifications by Enhanced DIA Libraries: Quantification in Murine Liver Disease

Robinson, AE;Binek, A;Venkatraman, V;Searle, BC;Holewinski, RJ;Rosenberger, G;Parker, SJ;Basisty, N;Xie, XS;Lund, PJ;Saxena, G;Mato, JM;Garcia, BA;Schilling, B;Lu, SC;Van Eyk, JE

JOURNAL OF PROTEOME RESEARCH

2020-10-02

Reciprocal Regulation Between Forkhead Box M1/NF-kappa B and Methionine Adenosyltransferase 1A Drives Liver Cancer

Li, Y;Lu, LQ;Tu, J;Zhang, J;Xiong, T;Fan, W;Wang, JH;Li, M;Chen, YB;Steggerda, J;Peng, H;Chen, YH;Li, TWH;Zhou, ZG;Mato, JM;Seki, E;Liu, T;Yang, HP;Lu, SC

HEPATOLOGY

2020-10-01

Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitisviaAMPK and mTOR regulation

Fernandez-Ramos, D;Lopitz-Otsoa, F;Delacruz-Villar, L;Bilbao, J;Pagano, M;Mosca, L;Bizkarguenaga, M;Serrano-Macia, M;Azkargorta, M;Iruarrizaga-Lejarreta, M;Sot, J;Tsvirkun, D;van Liempd, SM;Goni, ...

WORLD JOURNAL OF GASTROENTEROLOGY

2020-09-14

Abnormal concentration of porphyrins in serum from COVID-19 patients

San Juan, I;Bruzzone, C;Bizkarguenaga, M;Bernardo-Seisdedos, G;Lain, A;Gil-Redondo, R;Diercks, T;Gil-Martinez, J;Urquiza, P;Arana, E;Seco, M;de Vicuna, AG;Embade, N;Mato, JM;Millet, O

BRITISH JOURNAL OF HAEMATOLOGY

2020-08-29

PINE: An Automation Tool to Extract and Visualize Protein-Centric Functional Networks

Sundararaman, N;Go, J;Robinson, AE;Mato, JM;Lu, SC;Van Eyk, JE;Venkatraman, V

JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY

2020-07-01

H-1 NMR-Based Urine Metabolomics Reveals Signs of Enhanced Carbon and Nitrogen Recycling in Prostate Cancer

Bruzzone, C;Loizaga-Iriarte, A;Sanchez-Mosquera, P;Gil-Redondo, R;Astobiza, I;Diercks, T;Cortazar, AR;Ugalde-Olano, A;Schafer, H;Blanco, FJ;Unda, M;Cannet, C;Spraul, M;Mato, JM;Embade, N;Carracedo, ...

JOURNAL OF PROTEOME RESEARCH

2020-06-05

Targeting Hepatic Glutaminase 1 Ameliorates Non-alcoholic Steatohepatitis by Restoring Very-Low-Density Lipoprotein Triglyceride Assembly

Simon, J;Nunez-Garcia, M;Fernandez-Tussy, P;Barbier-Torres, L;Fernandez-Ramos, D;Gomez-Santos, B;Buque, X;Lopitz-Otsoa, F;Goikoetxea-Usandizaga, N;Serrano-Macia, M;Rodriguez-Agudo, R;Bizkarguenaga, ...

CELL METABOLISM

2020-03-03

Early treatment efficacy of S-adenosylmethionine in patients with intrahepatic cholestasis: A systematic review

Noureddin, M;Sander-Struckmeier, S;Mato, JM

WORLD JOURNAL OF HEPATOLOGY

2020-02-27