Metabolic Control

John Jones

PhD, Principal Investigator

The Metabolic Control Group integrates three labs headed by Carvalho, Jones and Salvador and performs research in areas relevant for lifestyle and aging-relevant chronic diseases:

  • Organization principles of biochemical systems: We seek to discover, understand and exploit generic rules that relate the design of biochemical systems to function, with redox signaling in human cells as a main focus of study.
  • Modeling blood-brain barrier (BBB) permeation. Failure to cross the BBB is the main attrition factor in developing psycho-active drugs. The bioavailability of xenobiotics at the brain is strongly affected by their interaction with lipid bilayers and blood components. Our work shows that the partition of drugs among the compartments strongly affects the timing and effectiveness of their BBB permeation We are modeling how molecular features of the xenobiotics impact on the kinetics of these critical steps and working to achieve better predictions of overall permeability.
  • Developing novel stable-isotope tracer methodologies for analysis of metabolic fluxes to study nutrient metabolism in physiological and pathophysiological conditions. These have been successfully translated into the clinical setting by the application of noninvasive "chemical biopsy" approaches for sampling hepatic metabolites.
  • Evaluating drug induced alterations in insulin action and intracellular signaling in peripheral tissues, inflammation and atherosclerosis by understanding the role and the impact of the adipocyte as an endocrine organ.
  • Investigating the importance of neuropeptides and insulin in skin wound healing and tissue regeneration in diabetes.
  • Investigating systemic and local factors that are altered in obesity and diabetes and identify dysfunctional pathways, such as mitochondrial function and ER stress in cells and tissues with the goal of enhancing early diagnosis of subjects at risk for chronic complications in order to improve/personalize treatment.

Group Members

Group Members

Group members are: John Jones (PhD, Principal Investigator), Ana Burgeiro (PhD), Ana Catarina Fonseca (PhD), Armindo Salvador (PhD), Aryane Pinho, Diana Santos, Ermelindo Leal (PhD), Eugenia Carvalho (PhD), Getachew Debas Belew, Giada Di Nunzio, Hugo Filipe (PhD), João Silva, João Rito, João Moura Alves (PhD), Ludgero Tavares (PhD), Maria Oliveira (PhD), Marija Petkovic, Raphael Beauchamp.

Selected Publications

Proteostasis in epicardial versus subcutaneous adipose tissue in heart failure subjects with and without diabetes. Burgeiro A, Fonseca AC, Espinoza D, Carvalho L, Lourenço N, Antunes M, Carvalho E. Biochim Biophys Acta. 2018 Apr 4;1864:2183‑2198.

Disposition of a Glucose Load into Hepatic Glycogen by Direct and Indirect Pathways in Juvenile Seabass and Seabream.Rito J, Viegas I, Pardal MA, Meton I, Baanante IV and Jones JG. Sci. Reports. 2018. 8, Article number: 464 doi:10.1038/s41598‑017‑19087‑y.

Mapping the phenotypic repertoire of the cytoplasmic 2‑Cys peroxiredoxin ‑ thioredoxin system: 1. Understanding commonalities and differences among cell types Selvaggio G, Coelho PMBM, Salvador A. Redox Biology 2018 15:297‑315 DOI:10.1016/j.redox.2017.12.008.

Localized Redox Relays as a Privileged Mode of Cytoplasmic Hydrogen Peroxide Signaling. Travasso RDM, Sampaio dos Aidos F, Bayani A, Abranches P and Salvador A. Redox Biology 2017 12:233‑245. DOI:10.1016/j.redox.2017.01.003.

Mechanisms by which the thiazolidinedione troglitazone protects against sucrose-induced hepatic fat accumulation and hyperinsulinemia. Martins FO, Delgado TC, Viegas J, Gaspar J, Scott DK, O’Doherty RM, Macedo MP and Jones JG. Br. J. Pharmacol. 2016 173, 267‑278.

Selected Grants

“Metabolic Dysfunctions associated with Pharmacological Treatment of Schizophrenia” Marie Sklodowska Curie Innovative Training Network H2020‑MSCA‑ITN‑2016‑721236 2017‑2020 €3,760,899. Co‑investigators: Eugenia Carvalho & John Jones.

“The Role of Visceral Fructose Metabolism in the Development of Non‑alcoholic Fatty Liver Disease.” CENTRO‑01‑0145‑FEDER‑028147 €236,184, June 1 2018‑May 31, 2021. PI: John Jones.

“Unraveling the Rules of Passive Permeation Through the Blood‑Brain Barrier” PTDC/DTP‑FTO/2784/2014, 2016‑2019. €199 680. Co‑investigator: Armindo Salvador.

“Assessment of oxidative capacity in obese children” NIGMS_NIH P20GM109096 NIH‑COBRE 2017‑2019. $9,700,000. Weber J. Program PI; Eugenia Carvalho PI of a primary project, $300,000.

“Effects of PTP1b modulation on Wound Healing, in vitro and in vivo systems” 17/0005621 Diabetes UK 2018‑2020. £165,000. Co‑investigator: Eugenia Carvalho.

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