Pablo Herrero Alfonso
Pablo Herrero Alfonso
Precision Medicine and Metabolism Lab
Address: Bizkaia Science and Technology Park, building 800, Derio (Bizkaia)

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 use of pharmacological chaperones in rare diseases caused by reduced protein stability

Gil-Martinez, J;Bernardo-Seisdedos, G;Mato, JM;Millet, O



ALAD Inhibition by Porphobilinogen Rationalizes the Accumulation of ?-Aminolevulinate in Acute Porphyrias br

San Juan, I;Pereira-Ortuzar, T;Cendoya, X;Lain, A;To-Figueras, J;Mateos, B;Planes, FJ;Bernardo-Seisdedos, G;Mato, JM;Millet, O



Inhibition of carnitine palmitoyltransferase 1A in hepatic stellate cells protects against fibrosis

Fondevila, MF;Fernandez, U;Heras, V;Parracho, T;Gonzalez-Rellan, MJ;Novoa, E;Porteiro, B;Alonso, C;Mayo, R;Lima, ND;Iglesias, C;Filliol, AA;Senra, A;Delgado, TC;Woodhoo, A;Herrero, L;Serra, ...



Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles

Martinez-Arranz, I;Bruzzone, C;Noureddin, M;Gil-Redondo, R;Minchole, I;Bizkarguenaga, M;Arretxe, E;Iruarrizaga-Lejarreta, M;Fernandez-Ramos, D;Lopitz-Otsoa, F;Mayo, R;Embade, N;Newberry, E;Mittendorf, ...



Exploration of Human Serum Lipoprotein Supramolecular Phospholipids Using Statistical Heterospectroscopy in n-Dimensions (SHY-n): Identification of Potential Cardiovascular Risk Biomarkers Related to SARS-CoV-2 Infection

Masuda, R;Lodge, S;Whiley, L;Gray, N;Lawler, N;Nitschke, P;Bong, SH;Kimhofer, T;Loo, RL;Boughton, B;Zeng, AX;Hall, D;Schaefer, H;Spraul, M;Dwivedi, G;Yeap, BB;Diercks, T;Bernardo-Seisdedos, ...



PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer

Zabala-Letona, A;Arruabarrena-Aristorena, A;Fernandez-Ruiz, S;Viera, C;Carlevaris, O;Ercilla, A;Mendizabal, I;Martin, T;Macchia, A;Camacho, L;Pujana-Vaquerizo, M;Sanchez-Mosquera, P;Torrano, ...



Depletion of mitochondrial methionine adenosyltransferase alpha 1 triggers mitochondrial dysfunction in alcohol-associated liver disease

Barbier-Torres, L;Murray, B;Yang, JW;Wang, JH;Matsuda, M;Robinson, A;Binek, A;Fan, W;Fernandez-Ramos, D;Lopitz-Otsoa, F;Luque-Urbano, M;Millet, O;Mavila, N;Peng, H;Ramani, K;Gottlieb, R;Sun, ...



J-Edited DIffusional Proton Nuclear Magnetic Resonance Spectroscopic Measurement of Glycoprotein and Supramolecular Phospholipid Biomarkers of Inflammation in Human Serum

Nitschke, P;Lodge, S;Kimhofer, T;Masuda, R;Bong, SH;Hall, D;Schafer, H;Spraul, M;Pompe, N;Diercks, T;Bernardo-Seisdedos, G;Mato, JM;Millet, O;Susic, D;Henry, A;El-Omar, EM;Holmes, E;Lindon, ...



S-adenosylmethionine inhibits la ribonucleoprotein domain family member 1 in murine liver and human liver cancer cells

Ramani, K;Robinson, AE;Berlind, J;Fan, W;Abeynayake, A;Binek, A;Barbier-Torres, L;Noureddin, M;Nissen, NN;Yildirim, Z;Erbay, E;Mato, JM;Van Eyk, JE;Lu, SC



Uneven metabolic and lipidomic profiles in recovered COVID-19 patients as investigated by plasma NMR metabolomics

Bizkarguenaga, M;Bruzzone, C;Gil-Redondo, R;SanJuan, I;Martin-Ruiz, I;Barriales, D;Palacios, A;Pasco, ST;Gonzalez-Valle, B;Lain, A;Herrera, L;Azkarate, A;Vesga, MA;Eguizabal, C;Anguita, J;Embade, ...