Jose Miguel Ramos Pittol, PhD

Junior Group Leader, Post-Doctoral Researcher

Institute of Biochemistry
University of Innsbruck
Room no. L.03.031

Center for Chemistry and Biomedicine (CCB) Innrain 80-82, 6020 Innsbruck / Austria
Phone: +43 512 507 - 57514 | Fax: +43 512 507 - 57599
Email: Jose.Ramos-Pittol@uibk.ac.at

ORCIDGoogle Scholar

Lab for metabolic diseases

The liver is a highly metabolically active organ that orchestrates the response to nutrient availability during fasting and feeding. Metabolic dysfunction–associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is the most prevalent chronic liver disease worldwide. In MASLD, hepatocytes excessively accumulate lipids, reflecting an impaired metabolic profile and response to nutrients. MASLD can progress to Metabolic dysfunction-associated steatohepatitis (MASH), where inflammation and fibrosis hamper hepatic functions and increase the risk of cirrhosis and cancer.

Our mission is to gain mechanistic insights into the etiology of NAFLD, and contribute to the development of novel therapies. We focus on the transcriptional reprogramming driven by metabolic alterations in NAFLD. We hypothesize that metabolic signalling and transcription factors cooperate to sustain disease progression and reduce therapy response. We study the microphtalmia (Mi/TFE) and nuclear receptor (NR) superfamilies at the genomic level in cell models of liver and gut, and advanced organoids.

Research interests

  • modelling of metabolic diseases in organoid and cell systems
  • (cross-)regulation of RXR-heterodimerizing NRs FXR, PPAR and TR
  • structural determinants of NR function
  • development of bio-assays for the analysis of protein modifications

Key methods

  • generation and use of gastrointestinal organoids as models of metabolic disease
  • (inducible) gene expression systems in cell culture
  • analysis of gene expression and genomic/transcriptomic data
  • production of recombinant proteins in eukaryotic cells and bacteria
  • manipulation of gene expression using CRISPR
  • flow cytometry and fluorometric method development

Employment/Experience

Academic experience

2024-present: Radiation Safety and Biological Safety Officer, Institute of Biochemistry, University of Innsbruck, Austria.

2020-present: Junior group leader in metabolic diseases and postdoc, Institute of Biochemistry, University of Innsbruck, Austria.

2015-2020: Postdoc in Molecular and translational metabolism. Lab of Prof. Dr. Saskia van Mil. University Medical Center Utrecht, The Netherlands.

2013-2014: Postdoc in transcription specificity. Lab of Dr Simona Saccani. Institute for Research on Cancer and Aging, Nice, France.

2013: PhD Defense (Dr. Rer. Nat.). Characterization of a novel transactivation domain of NF-κB p65. Alberts-Ludwig University Freiburg, Germany.

2009-2013: PhD studies. International Max-Planck research school- Molecular and cell biology (IMPRS-MCB). Lab of Dr. Simona Saccani. Max Planck Institute of Immunobiology and Epigenetics Freiburg, Germany.

2007-2009: Diploma studies (Dipl. Biol.). Thesis: Reactive nitrogen species in a model of neuronal apoptosis. Lab of Dr. Julio Morán. Universidad Nacional Autonoma de Mexico (UNAM), Mexico, and Alberts-Ludwig University Freiburg, Germany.

2002-2007: Bachelor studies. Investigación Biomédica Básica. Facultad de Medicina, Universidad Nacional Autonoma de Mexico (UNAM), Mexico.

Grant support and awards

2020-2023: TWF Nachwuchsförderung “Effects of chronic mTORC1 activation in hepatic FXR signalling”

2009-2013: International Max Planck Research School fellowship

2007-2012: DAAD-CONACyT Mexico-Germany graduate collaborative fellowship

Publications 

van der Veen SW, Dijkstra JJ, Willemsnen ECL, Houtman R, Milona A, Marchet N, Spit M, Hollman D, Zwartkruis FJT, Vermeulen M, Ramos Pittol JM#, van Mil SWC# (2024). The Farnesoid-X-Receptor activates transcription independently of RXR at non-canonical response elements. Nucleic Acids Research, gkae1214, December 2024. https://doi.org/10.1093/nar/gkae1214

Lopes T, Hope DCD, Ramos Pittol JM, Curtis A, Shrewsbury JV, Davies I, Zhou Z, Sardini A, Minnion JS, Dormann D, Bewick GA, Murphy KG, Carling D, Bloom SR, Tan TMM, Owen, BM (2024). Dietary protein defends lean mass and maintains the metabolic benefits of glucagon receptor agonism in mice. Molecular Metabolism 89, 102024, November 2024. https://doi.org/10.1016/j.molmet.2024.102024

Enric Mocholi, Laura Russo, Keshav Gopal, Andrew G Ramstead, Sophia M Hochrein, Harmjan R Vos, Geert Geeven, Adeolu O Adegoke, Anna Hoekstra, Robert M van Es, Jose Ramos Pittol, Sebastian Vastert, Jared Rutter, Timothy Radstake, Jorg van Loosdregt, Celia Berkers, Michal Mokry, Colin C Anderson, Ryan M O’Connell, Martin Vaeth, John Ussher, Boudewijn MT Burgering, Paul J Coffer Pyruvate metabolism controls chromatin remodeling during CD4+ T cell activation Cell reports. https://doi.org/10.1016/j.celrep.2023.112583

Ramos-Pittol JM, Fernandes-Freitas I, Milona A, Manchishi SM, Rainbow K, Lam BYH, Tadross JA, Beucher A, Colledge WH, Cebola I, Murphy KG, Miguel-Aliaga I, Yeo GSH, Dhillo WS, Owen BM. Dax1 modulates ERα-dependent hypothalamic estrogen sensing in female mice. Nat Commun. 2023 May 29;14(1):3076. https://doi.org/10.1038/s41467-023-38618-y

de Wit K, Beuers U, Mukha A, Stigter E, Gulersonmez CM, Ramos Pittol JM, Middendorp S, Takkenberg BR , van Mil SWC#. Rifaximin stimulates nitrogen detoxification by PXR-independent mechanisms in human small intestinal organoids. Liver International 2022. https://doi.org/10.1111/liv.15491

Stahl Madsen M*, Marjoleine Broekema MF*, Rønn Madsen M, Koppen A, Borgman A, Gräwe C, Thomsen EGK, Westland D, Kranendonk MEG, Groot Koerkamp M, Hamers N, Bonvin AMJJ, Ramos-Pittol JM, Nath Natarajan K, Kersten S, Holstege FCP, Monajemi H, van Mil SWC, Vermeulen M, Kragelund BB, Cassiman D, Mandrup S#, Kalkhoven E#. PPARγ lipodystrophy mutants reveal intermolecular interactions required for enhancer activation. Nature Communications 13:2022. https://doi.org/10.1038/s41467-022-34766-9

Moreno S, Ramos Pittol JM, Hartl M, Micura R#. Robust synthesis of 2′-azido modified RNA from 2′-amino precursors by diazotransfer reaction. Organic & Biomolecular Chemistry 39:2022. https://doi.org/10.1039/D2OB01560A

Abdellatif M, Trummer-Herbst V, Heberle AM, Humnig A, Pendl T, Durand S, Cerrato G, Hofer SJ, Islam M, Voglhuber J, Ramos Pittol JM, Kepp O, Hoefler G, Schmidt A, Rainer PP, Scherr D, Von Lewinski D, Bisping E, McMullen JR, Diwan A, Eisenberg T, Madeo F, Thedieck K, Kroemer G, Sedej S#. Fine-tuning cardiac insulin-like growth factor 1 receptor signaling to promote health and longevity. Circulation 25:2022 https://doi.org/10.1161/CIRCULATIONAHA.122.059863

Kwiatkowski M, Hotze M, Schumacher J, Asif AR, Ramos Pittol JM, Brenig B, Ramljak S, Zischler H, Herlyn H#. Protein speciation is likely to increase the chance of proteins to be determined in 2‐DE/MS. Electrophoresis 06:2022 https://doi.org/10.1002/elps.202000393

Cadena Sandoval M, Heberle AM, Rehbein U, Barile C, Ramos Pittol JM, Thedieck K. mTORC1 Crosstalk With Stress Granules in Aging and Age-Related Diseases. Front Aging. 2021 Oct 13;2. https://doi.org/10.3389/fragi.2021.761333

Orea-Soufi A, Castillo-Lluva S, Salvador-Tormo N, Martín-Cabrera P, Recuero S, Gabicagogeascoa E, Moreno-Valladares M, Mendiburu-Eliçabe M, Blanco-Gómez A, Ramos-Pittol JM, García-Taboada E, Ocaña A, Cimas FJ, Matheu A, Álvarez-López I, Velasco G, Lorente M. The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer. Cancers (Basel). 2021 Oct 22;13(21):5307. https://doi.org/10.3390/cancers13215307

Ijssennagger N, van Rooijen KS, Magnúsdóttir S, Ramos Pittol JM, Willemsen ECL, de Zoete MR, Baars MJD, Stege PB, Colliva C, Pellicciari R, Youssef SA, de Bruin A, Vercoulen Y, Kuipers F, van Mil SWC. Ablation of liver Fxr results in an increased colonic mucus barrier in mice. JHEP Rep. 2021 Aug 4;3(5):100344. https://doi.org/10.1016/j.jhepr.2021.100344

 Prentzell MT *, Rehbein U *, Cadena Sandoval M *, De Meulemeester AS *, Baumeister R, Brohée L, Berdel B, Bockwoldt M, Carroll B, Chowdhury SR, von Deimling A, Demetriades C, Figlia G; Genomics England Research Consortium, de Araujo MEG, Heberle AM, Heiland I, Holzwarth B, Huber LA, Jaworski J, Kedra M, Kern K, Kopach A, Korolchuk VI, van 't Land-Kuper I, Macias M, Nellist M, Palm W, Pusch S, Ramos Pittol JM, Reil M, Reintjes A, Reuter F, Sampson JR, Scheldeman C, Siekierska A, Stefan E, Teleman AA, Thomas LE, Torres-Quesada O, Trump S, West HD, de Witte P, Woltering S, Yordanov TE, Zmorzynska J, Opitz CA, Thedieck K. G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling. Cell. 2021 Feb 4;184(3):655-674.e27. https://doi.org/10.1016/j.cell.2020.12.024

Ramos Pittol JM, Milona A, Morris I, Willemsen ECL, van derVeen SW, Kalkhoven E, van Mil SWC. FXR isoforms control distinct hepatic metabolic functions via selective DNA binding. Gastroenterology, Nov 2020.https://doi.org/10.1053/j.gastro.2020.07.036

Milona A, Massafra V, Vos H, Naik J, Artigas N, Paterson H, Bijsmans ITGW, Willemsen ECL, Ramos Pittol JM, Miguel-Aliaga I, Bosma P, Burgering B, Williamson C, Vernia S, Dhillo WS, van Mil SWC, Owen BM. Steroidogenic Control of Liver Metabolism Through a Nuclear Receptor-Network. Molecular Metabolism, September 2019. https://doi.org/10.1016/j.molmet.2019.09.007

 Passeri D *, Carotti A *, Ramos Pittol JM, Ciaccioli G, Pellicciari G, van Mil SWC, Gioiello A. Dissecting the allosteric FXR modulation: a chemical biology approach using guggulsterone as a chemical tool. MedChemComm, June 2019. https://doi.org/10.1039/C9MD00264B

Ramos Pittol JM, Oruba A, Mittler G, Saccani S, van Essen D. Zbtb7a transduces control of promoter accessibility by diverse transcription factors. PLOS Biology, May 2018. https://doi.org/10.1371/journal.pbio.2004526

Massafra V, Milona A, Vos HR, Ramos RJJ, Gerrits J, Willemsen ECL, Ramos Pittol JM, Ijssennagger N, Houweling M, Prinsen HCMT, Verhoeven-Duif NM, Burgering BMT, van Mil SWC. Farnesoid X Receptor Activation Promotes Hepatic Amino Acid Catabolism and Ammonium Clearance in Mice. Gastroenterology, May 2017. https://doi.org/10.1053/j.gastro.2017.01.014

Bijsmans IT, Milona A, Ijssennagger N, Willemsen EC, Ramos Pittol JM, Jonker JW, Lange K, Hooiveld GJ, van Mil SW. Characterization of stem cell-derived liver and intestinal organoids as a model system to study nuclear receptor biology. Biochim Biophys Acta, March 2017. https://doi.org/10.1016/j.bbadis.2016.12.004

 Ijssennagger N, Janssen AW, Milona A, Ramos Pittol JM, Hollman DA, Mokry M, Betzel B, Berends FJ, Janssen IM, van Mil SW, Kersten S. Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid. J Hepatology, May 2016. https://doi.org/10.1016/j.jhep.2016.01.016

 Olguín-Albuerne M, Ramos-Pittol JM, Coyoy A, Martínez-Briseño CP, Domínguez G, Morán J. Peroxynitrite is Involved in the Apoptotic Death of Cultured Cerebellar Granule Neurons Induced by Staurosporine, but not by Potassium Deprivation. Neurochem Res, February 2016. https://doi.org/10.1007/s11064-015-1805-9

Massafra V, Ijssennagger N, Plantinga M, Milona A, Ramos Pittol JM, Boes M, van Mil SW. Splenic dendritic cell involvement in FXR-mediated amelioration of DSS colitis. Biochim Biophys Acta, February 2016. https://doi.org/10.1016/j.bbadis.2015.11.001

Bijsmans IT, Guercini C, Ramos Pittol JM, Omta W, Milona A, Lelieveld D, Egan DA, Pellicciari R, Gioiello A, van Mil SW. The glucocorticoid mometasone furoate is a novel FXR ligand that decreases inflammatory but not metabolic gene expression. Sci Rep, September 2015. https://doi.org/10.1038/srep14086

 *Equal contribution, # Corresponding author

Bachelor or Master Thesis on transcriptional regulation:

For more information please contact Jose.Ramos-Pittol@uibk.ac.at

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