CCBIO Seminar – Mark LaBarge

The seminar (webinar) is open to all.

Speaker: Mark LaBarge, Department of Population Sciences, Beckman Research Institute at City of Hope, Duarte, CA, USA

Title: "Epigenetic priming in mammary epithelia underlies susceptibility to age-related cancers: causes, consequences, and countermeasures"

Place: digital event as webinar in Zoom. Please use this link to get access: https://uib.zoom.us/j/64063131856?pwd=bkcyVWxVMzhsQm85UEFNdTdvN1VDZz09No password is required. You can start to register from 14:20, we start the webinar at 14:30.NOTE: please change any username to your name in the logon process, so that chair can address you by name if you have questions. All audience will by default be muted and without video. Chair will de-mute your microphone if you have a question, please use raise hands or chat funtions for questions. (Question session is after the talk.)

Time: February 25, 2021 at 14:30 (Norwegian time zone)

Chair: Agnete Engelsen

Short bio: Mark LaBarge is a Professor and cell biologist in the Department of Population Sciences at the Beckman Research Institute at City of Hope National Medical Center, which is near Los Angeles in California, USA. Dr. LaBarge’s work focuses on understanding how aging makes mammary epithelia more susceptible to cancer initiation.  His lab uses combinations of primary cell and organoid culture with technologies for precision manipulation of the microenvironment to deeply characterize the effects of aging in human mammary epithelia, and to probe the functional consequences of those changes. In recognition of his work, Dr. LaBarge is the recipient of the Era of Hope Scholar Award, and he is the Associate Director and co-founder of the Center for Cancer and Aging at City of Hope.

Mark is also one of CCBIO's international affiliated investigators.

Abstract: 

Aging causes molecular changes that manifest as stereotypical phenotypes yet aging-associated diseases progress only in certain individuals. At lineage-specific resolution, we show how directional and variant age-dependent changes are integrated in mammary epithelia to generate a stereotypical phenotype in luminal epithelial cells - the cancer cell of origin for age-related breast cancers. Strikingly,  >94% of all the age-related directional changes in the entire mammary epithelium occur only in luminal epithelial cells, whereas neighboring myoepithelial cells exhibit little obvious change. Increased variance in DNA methylation leads to epigenetic priming for future events that are more directly related to cancer progression, such as demethylation of ESR1-binding regions in DNAm-regulatory CXXC5 in older luminal cells and luminal-subtype cancers. Acceleration of age-dependent directional changes in luminal lineage-specific transcription factors, such as ELF5, distinguished women who were at exceedingly high risk of breast cancer thus establishing a connection between specific age-dependent changes and cancer susceptibility. At the proteome level up-regulation of basal markers in luminal cells, including KRT14 and AXL, are a prominent consequence of aging, and DDR1-PEAK1 was identified as an age-dependent signaling kinase in luminal cells, which revealed a potential age-dependent vulnerability for targeted ablation of cancer cells of origin. We hypothesize that increased variance with age in gene expression and DNA methylation explains why some women get breast cancer and others do not, and that some specific directional changes will help to distinguish the women who go on to get age-dependent cancer from those who do not. We are exploring age-dependent changes for applications as risk biomarkers and prevention targets.