Biotrack

Molecular and metabolic determinants of endothelial dysfunction in endocrine diseases: The Cushing model

REF: PD 29
Principle investigator:
Felicia A. Hanzu
Contact details:

fhanzu(ELIMINAR)@clinic.ub.es

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Research framework

The main aim of the proposal is to investigate the major determinants of the endothelial dysfunction associated to endocrine diseases. Cushing syndrome has a high impact in cardiovascular complications and this impact persists after the cure of the disease.

We postulate that epigenetic modifications in blood peripheral cells during active disease induced by the endogenous hypercortisolism are persisting years after cure, supporting the concept of metabolic memory and maintaining a proinflammatory deleterious environment at the arterial endothelium.

Therefore, we are investigating ex-vivo, in peripheral blood cells from Cushing syndrome patients and control subjects, the epigenetic changes in several regions of DNA. On the other hand, we are studying, in vitro, in a human model of endothelial cell in culture, the impact of molecular determinants and metabolites of serum of Cushing syndrome patients and obese and lean controls on endothelial dysfunction and thrombogenesis. Implicated pathways will be determined using molecular biology approaches.

Techniques most used: Genomic and epigenetic analysis (chromatin immune precipitation, rt-PCR, RNA and protein arrays), flow cytometry (peripheral blood cell sorting),immunocytochemistry, cell culture, perfusion studies.

The following publications can support our work:

  1. F.A. Hanzu, MM. Musri, Y. Esteban, P. Kaliman, R. Gomis, M. Párrizas.”Histone demethylase LSD1 represses an inflammatory program in preadipocytes.” J Biol Chem, en revision.
  2. F.A. Hanzu, M. Palomo, S. Kalko, M. Parrizas, M. Garaulet, G. Escolar, R. Gomis, M.Diaz-Ricart “Translational evidence of endothelial damage in obese individuals: inflammatory and prothrombotic responses”, J Thromb Haemost., 9(6):1236-45. 2011.
  3. MM. Musri, MC. Carmona, F.A. Hanzu, P. Kaliman, R. Gomis, M. Párrizas “Histone demethylase LSD1 regulates adipogenesis”.J Biol Chem, 24; 285(39):30034-41, 2010.

Our group is focused on translational research being constituted by MD and PhD with the goal to achieve knowledge to prevent and treat endocrine diseases.

The group has access to all core facilities of IDIBAPS (ww.idibaps.org) to samples and data of the Biobanc and has collaborative relationships with Metabolomic and Transcriptomic platforms.

Keywords

Endocrinology, epigenetics, endothelium, blood cells, hypercortisolism, inflammation.

Main Challenges

The main goal of our research is to understand and prevent the mechanisms by which the prolonged hypercortisolism can induce after remission a sustained atherothrombotic injury. Epigenetic inheritance is an important mechanism in the understanding of complex metabolic diseases.

The inhibition of enzymatic activities involved in non-genomic chromatin changes, changes designed for the pharmacological induction or the silencing of transcription of deleterious genes in target cells could represent a natural prophylaxis form in the development of the atherothrombotic disease.

The candidate to be integrated in our group must therefore be highly motivated, interested in translational biomedical research, with a previous experience in molecular biology and biochemistry.

Research experience in epigenetics, peripheral blood cells, endothelial dysfunction, inflammation, atherosclerosis and general immunology is particularly valued .

Regular debates with other colleagues are mandatory in order to obtain highlights of novelty in the area of research.

Team strategic objective in IDIBAPS

Translational research with the aim to prevent and treat endocrine diseases.

(Read eligibility criteria)