Molecular Ageing
Celia P. Martinez-Jimenez Lab
Celia's team applies single-cell approaches to interrogate molecular features as predictor of molecular age. The assessment of intra-organ cell-to-cell variability will instruct precision diagnostics and personalized treatments.
Celia's team applies single-cell approaches to interrogate molecular features as predictor of molecular age. The assessment of intra-organ cell-to-cell variability will instruct precision diagnostics and personalized treatments.
About our Research
Advances in genomic, epigenomic and transcriptomic technologies are opening a new era for understanding the molecular mechanisms underlying organismal ageing. We aim to accelerate the development of anti-ageing interventions to prevent age-related diseases.
Our lab is interested in understanding the role of cellular heterogeneity on tissue function.In particular, we focus on the common molecular mechanisms between ageing and chronic liver diseases, and we develop novel methodologies to study the impact of age-related cellular heterogeneity in the development and progression of chronic diseases.
Studying complex biological processes at high resolution
Ageing is characterised by the progressive decline of physiological and cellular functions. However, ageing is a heterogeneous process between and within organs, tissues and cells.
Ageing and Chronic Diseases: common molecular signatures
The “Silver Tsunami”, is a metaphor used to describe global population ageing, including the alarming numbers and the overwhelming health and economic implications. The ageing population is more susceptible to growing environmental challenges - such as climate change, air pollution or newly emerging pathogens, as well as adverse drug reactions causing a much higher percentage of hospital admissions compared to younger individuals. Our current predictive tools to anticipate the impact of ageing at the cellular levels yet remains under development. Towards this larger goal, our research aims 1) to characterize the molecular mechanisms of ageing with cellular resolution; 2) to develop diagnostic-tools to study drug metabolism and toxicity in ageing and age-related liver pathologies, and 3) to model ageing in vitro using 3D- organoids to harmonize anti-ageing interventions and perform functional assays to understand the complex process of ageing.
Research lines
-
Cellular heterogeneity and disease susceptibility
We investigate how cellular heterogeneity affects tissue function and whether cell-to-cell variability increases disease susceptibility. -
Accelerated ageing
It has been shown that life style, dietary interventions and chronic diseases accelerate the ageing phenotype. We aim to dissect the molecular signatures that are associated with accelerated ageing under different conditions. -
Ageing and epigenetics
To further understand the precise molecular mechanisms leading to cellular heterogeneity, we investigate the upstream epigenetic landscape of individual cells using single-cell multiomic approaches. -
Ageing "in vitro"
On one hand, ageing in humans is difficult to study with many cofounding factors along their lifespan. On the other hand, model organisms do not fully recapitulate the phenotypes associated to human diseases. We aim to develop 3D-organoids that recapitulate molecular features of ageing to establish functional assays, and assess anti-ageing therapeutic interventions.
Publications
Makris, K. ; Fonda, V. ; Ramadhani, F.F. ; Fadel, L. ; Davezac, M. ; Payet, B. ; Deligiannis, I.K. ; Zhang, L. ; Horn, T. ; Heimerl, L. ; Jouffe, C. ; Heddes, M. ; Martinez Jimenez, C.P. ; Quagliarini, F. ; Uhlenhaut, N.H.
Hepatic metabolic reprogramming in male mice during short-term caloric restriction involves enhanced glucocorticoid rhythms.Neckermann, L. ; Erdösi, P. ; Zhang, L. ; Assum, I. ; Dropmann, A. ; Alaoua, S. ; Büttner, M. ; Lin, T. ; Gerstner, M. ; Ebert, M.P. ; Bantel, H. ; Dooley, S. ; Kluth, A. ; Menden, M.P. ; Martinez Jimenez, C.P. ; Hammad, S.
Preclinical evaluation of human ABCB5+ skin-derived stem cells reveals regenerative mechanisms and prognostic markers in a novel ACLF mouse model.Lin, M. ; Zhang, L. ; Wang, Z. ; Liu, H. ; Wang, K. ; Tang, G. ; Wang, W. ; Sun, P.
A combined system with convolutional neural networks and transformers for automated quantification of left ventricular ejection fraction from 2D echocardiographic images.Palmer, J.A. ; Rosenthal, N. ; Teichmann, S.A. ; Litvinukova, M.
Revisiting cardiac biology in the rra of single cell and spatial omics.Yin, K. ; Büttner, M. ; Deligiannis, I.K. ; Strzelecki, M. ; Zhang, L. ; Talavera Lopez, C.N. ; Theis, F.J. ; Odom, D.T. ; Martinez Jimenez, C.P.
Polyploidisation pleiotropically buffers ageing in hepatocytes.Sánchez Quant, E.S. ; Richter, M. ; Colomé-Tatché, M. ; Martinez Jimenez, C.P.
Single-cell metabolic profiling reveals subgroups of primary human hepatocytes with heterogeneous responses to drug challenge.Gruber, T. ; Contreras, R. ; Sánchez Quant, E.S. ; Miok, V. ; Makris, K. ; Le Thuc, O. ; Gonzales García, I. ; Garcia-Clavé, E. ; Althammer, F. ; Krabichler, Q. ; DeCamp, L.M. ; Jones, R.G. ; Lutter, D. ; Williams, R.H. ; Pfluger, P.T. ; Müller, T.D. ; Woods, S.C. ; Pospisilik, J.A. ; Martinez-Jimenez, C.P. ; Tschöp, M.H. ; Grinevich, V. ; García-Cáceres, C.
High-calorie diets uncouple hypothalamic oxytocin neurons from a gut-to-brain satiation pathway via κ-opioid signaling.Wirth, J. ; Huber, N. ; Yin, K. ; Brood, S. ; Chang, S.C.-E. ; Martinez Jimenez, C.P. ; Meier, M.
Spatial transcriptomics using multiplexed deterministic barcoding in tissue.Kolabas, Z.I. ; Kuemmerle, L. ; Perneczky, R. ; Förstera, B. ; Ulukaya, S. ; Ali, M. ; Kapoor, S. ; Bartos, L.M. ; Büttner, M. ; Caliskan, Ö.S. ; Rong, Z. ; Mai, H. ; Höher, L. ; Jeridi, D. ; Molbay, M. ; Khalin, I. ; Deligiannis, I.K. ; Negwer, M. ; Roberts, K. ; Simats, A. ; Carofiglio, O. ; Todorov, M.I. ; Horvath, I. ; Öztürk, F. ; Hummel, S. ; Biechele, G. ; Zatcepin, A. ; Unterrainer, M. ; Gnörich, J. ; Roodselaar, J. ; Shrouder, J. ; Khosravani, P. ; Tast, B. ; Richter, L. ; Díaz-Marugán, L. ; Kaltenecker, D. ; Lux, L. ; Chen, Y. ; Zhao, S. ; Rauchmann, B.S. ; Sterr, M. ; Kunze, I. ; Stanic Aguilera, K.N. ; Kan, V.W.Y. ; Besson-Girard, S. ; Katzdobler, S. ; Palleis, C. ; Schädler, J. ; Paetzold, J.C. ; Liebscher, S. ; Hauser, A.E. ; Gokce, O. ; Lickert, H. ; Steinke, H. ; Benakis, C. ; Braun, C. ; Martinez Jimenez, C.P. ; Buerger, K. ; Albert, N.L. ; Höglinger, G. ; Levin, J. ; Haass, C. ; Kopczak, A. ; Dichgans, M. ; Havla, J. ; Kümpfel, T. ; Kerschensteiner, M. ; Schifferer, M. ; Simons, M. ; Liesz, A. ; Krahmer, N. ; Bayraktar, O.A. ; Franzmeier, N. ; Plesnila, N. ; Erener, S. ; Puelles, V.G. ; Delbridge, C. ; Bhatia, H.S. ; Hellal, F. ; Elsner, M. ; Bechmann, I. ; Ondruschka, B. ; Brendel, M. ; Theis, F.J. ; Ertürk, A.
Distinct molecular profiles of skull bone marrow in health and neurological disorders.Alvarez, L. ; Marín-García, P.J. ; Rentero-Garrido, P. ; Martinez Jimenez, C.P. ; Llobat, L.
Interleukin 6 and interferon gamma haplotypes are related to cytokine serum levels in dogs in an endemic Leishmania infantum region.Strzelecki, M. ; Yin, K. ; Talavera Lopez, C.N. ; Martinez Jimenez, C.P.
Isolation of nuclei from flash-frozen liver tissue for single-cell multiomics.Wolff, G. ; Sakurai, M. ; Mhamane, A. ; Troullinaki, M. ; Maida, A. ; Deligiannis, I.K. ; Yin, K. ; Weber, P. ; Morgenstern, J. ; Wieder, A. ; Kwon, Y. ; Sekar, R. ; Zeigerer, A. ; Roden, M. ; Blüher, M. ; Volk, N. ; Poth, T. ; Hackert, T. ; Wiedmann, L. ; De Angelis Rigotti, F. ; Rodriguez-Vita, J. ; Fischer, A. ; Mukthavaram, R. ; Limphong, P. ; Tachikawa, K. ; Karmali, P. ; Payne, J. ; Chivukula, P. ; Ekim Üstünel, B. ; Martinez Jimenez, C.P. ; Szendrödi, J. ; Nawroth, P.P. ; Herzig, S.
Hepatocyte-specific activity of TSC22D4 triggers progressive NAFLD by impairing mitochondrial function.Yin, K. ; Patten, D. ; Gough, S.C. ; de Barros Gonçalves, S. ; Chan, A. ; Olan, I. ; Cassidy, L. ; Poblocka, M. ; Zhu, H. ; Lun, A. ; Schuijs, M.J. ; Young, A. ; Martinez Jimenez, C.P. ; Halim, T.Y.F. ; Shetty, S. ; Narita, M. ; Hoare, M.
Senescence-induced endothelial phenotypes underpin immune-mediated senescence surveillance.Richter, M. ; Deligiannis, I.K. ; Yin, K. ; Danese, A. ; Lleshi, E. ; Coupland, P. ; Vallejos, C.A. ; Matchett, K.P. ; Henderson, N.C. ; Colomé-Tatché, M. ; Martinez Jimenez, C.P.
Single-nucleus RNA-seq2 reveals functional crosstalk between liver zonation and ploidy.Kamies, R. ; Martinez Jimenez, C.P.
Advances of single-cell genomics and epigenomics in human disease: Where are we now?Chen, H.C. ; Eling, N. ; Martinez Jimenez, C.P. ; O'Brien, L.M. ; Carbonaro, V. ; Marioni, J.C. ; Odom, D.T. ; de la Roche, M.
IL-7-dependent compositional changes within the gamma delta T cell pool in lymph nodes during ageing lead to an unbalanced anti-tumour response.Martinez Jimenez, C.P. ; Eling, N. ; Chen, H.-C ; Vallejos, C.A. ; Kolodziejczyk, A.A. ; Connor, F. ; Stojic, L. ; Rayner, T.F. ; Stubbington, M.J.T. ; Teichmann, S.A. ; de la Roche, M. ; Marioni, J.C. ; Odom, D.T.
Aging increases cell-to-cell transcriptional variability upon immune stimulation.Schmidt, D. ; Wilson, M.D. ; Ballester, B. ; Schwalie, P.C. ; Brown, G.D. ; Marshall, A. ; Kutter, C. ; Watt, S. ; Martinez Jimenez, C.P. ; Mackay, S. ; Talianidis, I. ; Flicek, P. ; Odom, D.T.
Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding.Contact PioneerCampus
