Senescent cells that accumulate in our bodies are a major cause of health problems and enable cancer development as we age. Researchers at Cleara discovered the mechanism how senescent cells escape the natural elimination process. Based on this discovery, Cleara has succesfully developed and optimized therapeutics to treat patients with a range of diseases caused by this failure to clear senescent cells.
Discovery timeline
Investigation of biomarkers
Every cell in our body has the potential to become senescent as a consequence of various stresses. By unraveling the enormous heterogeneity of senescent cells, our researchers at Cleara identified the genes at the core of the senescence program. In addition, we obtained evidence for the existence of senescence “subtypes” which play different roles in disease development. Based on these discoveries, Cleara is developing new senescence biomarkers for diagnostics and drug targeting.
2012 | Identification of a novel biomarker for senescent cells — the nuclear loss of LaminB1 (Freund et al, 2012, JBC) |
2013 | Generation and characterization of a transgenic mouse model to report senescence and to study the effect of senescence clearance ( US Patent App. 15/067,543, US Patent 9,901,080, US Patent App. 14/365,040) |
2014 | Discovery of a new type of p16+ senescent cells associated to cutaneous wound healing which are associated to a very unique secretory phenotype (Demaria et al, 2014, Dev Cell) |
2016 | Demonstration that removing senescent cells ameliorate healthspan and reduce tumor progression after treatment with genotoxic therapies (Demaria et al, 2017, Can Discovery) |
2017 | Comprehensive study on the transcriptional heterogeneity of senescent cells and identification of a senescence-associated signature (Hernandez-Segura et al, 2017, Current Biology) |
2017 | Discovery that highly inflammatory (SASP positive) senescent cells are prone to anti-senescence treatment with FOXO4-p53 drugs (Baar et al, 2017, Cell) |
Cleara, the company
At Cleara Biotech, we are highly motivated to develop safe and effective treatments to counter the negative aspects of aging and target diseases like therapy-resistant late stage cancer. We aim to do so by generating compounds that are capable of selectively eliminating senescent and senescent-like cancer cells. Cleara Biotech is the exciting result of a long and proven academic history of the key members of our scientific team.
Aging is the most dominant risk factor for the majority of diseases.
Scientific Founder – Peter de Keizer, PhD
Team
Relevant papers
Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Baar MP, Brandt RMC, Putavet DA, Klein JDD, Derks KWJ, Bourgeois BRM, Stryeck S, Rijksen Y, van Willigenburg H, Feijtel DA, van der Pluijm I, Essers J, van Cappellen WA, van IJcken WF, Houtsmuller AB, Pothof J, de Bruin RWF, Madl T, Hoeijmakers JHJ, Campisi J, de Keizer PLJ. Cell. 2017 PMID: 28340339
Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse. Demaria M, O’Leary MN, Chang J, Shao L, Liu S, Alimirah F, Koenig K, Le C, Mitin N, Deal AM, Alston S, Academia EC, Kilmarx S, Valdovinos A, Wang B, de Bruin A, Kennedy BK, Melov S, Zhou D, Sharpless NE, Muss H, Campisi J. Cancer Discov. 2017 PMID: 27979832
Hallmarks of Cellular Senescence. Hernandez-Segura A, Nehme J, Demaria M. Trends Cell Biol. 2018 PMID: 29477613
The Fountain of Youth by Targeting Senescent Cells? de Keizer PL. Trends Mol Med. 2017 PMID: 28041781
Therapeutic interventions for aging: the case of cellular senescence. Soto-Gamez A, Demaria M. Drug Discov Today. 2017 PMID: 28111332
Unmasking Transcriptional Heterogeneity in Senescent Cells. Hernandez-Segura A, de Jong TV, Melov S, Guryev V, Campisi J, Demaria M. Curr Biol. 2017 PMID: 28844647
Targeted inhibition of metastatic melanoma through interference with Pin1-FOXM1 signaling. Kruiswijk F, Hasenfuss SC, Sivapatham R, Baar MP, Putavet D, Naipal KA, van den Broek NJ, Kruit W, van der Spek PJ, van Gent DC, Brenkman AB, Campisi J, Burgering BM, Hoeijmakers JH, de Keizer PL. Oncogene. 2016 PMID: 26279295
An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Demaria M, Ohtani N, Youssef SA, Rodier F, Toussaint W, Mitchell JR, Laberge RM, Vijg J, Van Steeg H, Dollé M, Hoeijmakers J, deBruin A, Hara E, Campisi J. Developmental Cell. 2014. 31:722-33. PMID: 25499914
Forkhead box o as a sensor, mediator, and regulator of redox signaling. de Keizer PL, Burgering BM, Dansen TB. Antioxid Redox Signal. 2011 PMID: 20626320
Activation of forkhead box O transcription factors by oncogenic BRAF promotes p21cip1-dependent senescence. de Keizer PL, Packer LM, Szypowska AA, Riedl-Polderman PE, van den Broek NJ, de Bruin A, Dansen TB, Marais R, Brenkman AB, Burgering BM. Cancer Res. 2010 PMID: 20959475
p53: Pro-aging or pro-longevity? de Keizer PL, Laberge RM, Campisi J. Aging (Albany NY). 2010 PMID: 20657035
Mdm2 induces mono-ubiquitination of FOXO4. Brenkman AB, de Keizer PL, van den Broek NJ, Jochemsen AG, Burgering BM. PLoS One. 2008 PMID: 18665269
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