Postdoc Position - Metabolic risk factors of sporadic ALS

USP-CEU welcomes early stage postdoctoral researchers with an excellent track record, to apply to the European Commission Marie Sklodowska-Curie (MSCA-24) Postodoctoral Felloships or any other R2 reseach calls, such as: Juan de la Cierva (Spanish Plan for Scientific and Technical Research and Innovation) or Atracción Talento (Madrid Regional Goverment).

Selected candidates will be provided with special assistance for proposal writing and development. Our University has been beneficiary of 7 MSCA PF since 2017, including one MSCA-PF with an evaluation of 100/100 in 2021.

Hosting Supervisor: Carmen Fernandez-Martos PhD, Orcid

PI Fernandez-Martos’s career investigates pathological mechanisms in Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and other neurodegenerative conditions. She has a broad experience in molecular endocrinology and extensive training in translational neuroscience with a focus on leptin therapies. Her background also includes works on in vivodisease models. PI Fernandez-Martos is currently A/Professor at the School of Pharmacy of USP-CEU and in this role leads her own laboratory group consisting of two A/Professors, with a background in aging research, one experienced research assistant and 1 PhD student under her primary supervision. Together they have extensive expertise in histological and biochemical techniques relevant to this proposal. She works closely with eminent researchers in the field of Chemistry (e.g. Drs. Santiago Gómez-Ruiz) and ALS/FTD (e.g. Drs. Anna King, James Vickers and Jeemen Sreedharan), to define new strategies focused on the control of metabolic status to reduce damage in ALS, with a focus on leptin.

Relevant publications:

1) Design of Mesoporous Silica Nanoparticles for the Treatment of Amyotrophic Lateral Sclerosis (ALS) with a Therapeutic Cocktail Based on Leptin and Pioglitazone. ACS Biomater Sci Eng. 2022 Nov 14;8(11):4838-4849. doi: 10.1021/acsbiomaterials.2c00865. 

2) Ozone modified hypothalamic signaling enhancing thermogenesis in the TDP-43A315T transgenic model of Amyotrophic Lateral Sclerosis. Sci Rep. 2022 Dec 2;12(1):20814. doi: 10.1038/s41598-022-25033-4.

3) The potential benefit of leptin therapy against amyotrophic lateral sclerosis (ALS). Brain Behav. 2022 Jan;12(1):e2465. doi: 10.1002/brb3.2465.

4) Alterations in Leptin Signaling in Amyotrophic Lateral Sclerosis (ALS). Int J Mol Sci. 2021 Sep 24;22(19):10305. doi: 10.3390/ijms221910305.

5) Enhanced Anti-Amyloid Effect of Combined Leptin and Pioglitazone in APP/PS1 Transgenic Mice. Curr Alzheimer Res. 2020;17(14):1294-1301. doi: 10.2174/1567205018666210218163857. 

Research topic description:

There is no cure for ALS. This devastating disorder is considered the third most common neurodegenerative disease worldwide, and is becoming a disease with a significant socio-economic impact and much community awareness for many countries across the globe. The rapid disease course, and the severity of unmet medical needs demand for new effective therapies that improve the lives of people living with ALS.

New data suggest that being overweight or obese confers a survival advantage in ALS patients, and this metabolic alteration directly affects leptin -a fat cell-derived hormone that regulates body weight. A recent epidemiological study has determined how leptin levels are inversely associated with ALS risk: increasing leptin concentrations were associated with longer survival of ALS patients, suggesting a possible link between leptin and the clinical features of ALS. However, there is little mechanistic insight into how leptin confers a survival advantage in patients with ALS.

My group has provided the first experimental evidence suggesting that ALS may be associated with alterations in leptin signaling pathways that might result in a leptin resistant state and that this could play a critical role in the characteristic irreversible and progressive pathological changes associated with ALS. Our hypothesis is that leptin triggers neuronal signalling pathways which protect against ALS pathology.

Exploiting highly relevant models of ALS pathology and chemical tools for drug discovery, the main aim of this project is demonstrate the relevance of our hypothesis to human disease using primary upper motor neurons cultures and hiPSC-derived neurons, to deliver unprecedented mechanistic insights into the role of leptin in ALS pathogenesis, and the basis for future drug or biomarker development, which is likely the most limiting factor for treatment development at this time.

Candidate requirements:

• Background in Neuroscience field, preferentially background in neurodegenerative diseases (NDDs) such as ALS, FTD and/or AD.
• Strong expertise in vitro in primary culture and culturing motor neurons, and in vivo disease models as well as human tissue.

An expression of interest shall be sent to Carmen Fernandez-Martos. Your file should contain the following elements:

1.  A short CV (Max. 2 pages)
2. Two letters of reference.

For MSCA-PF 24 call, at the deadline for the submission of proposals (11/09/2024) candidates must not have resided or carried out their main activities in Spain or more than 12 months in the 3 years immediately prior to the abovementioned deadline.

Those files received before 15th of June y will be considered for MSCA-PF 2024 call. Applications received after this date, will be considered for other calls after discussion with the candidate.

Keywords: Neurodegenerative disease (NDD); Amyotrophic lateral sclerosis (ALS); Metabolic alterations; Leptin; Biomarkers.