Deutsch Intern
    Chair of orthopedic

    Chromatin modifying factors and osteoporosis

    Chromatin modifying factors and osteoporosis

    Group members
    PD Dr. rer. nat. Regina Ebert
    Dr. Peggy Benisch
    M.Sc. Andrea Nicklas

    Principal investigator
    Prof. Dr. med. Matthias Becker
    Prof. Dr. med. Franz Jakob

    Age-associated modifications of chromatin structure and the resulting changes in gene regulation patterns are underlying causes of aging and age-related diseases like osteoporosis, atherosclerosis and tumor development. Chromatin regulators such as Polycomb group Protein BMI1 and Lymphocyte-specific helicase (LSH/HELLS/SMARCA6/PASG) are key regulators of chromatin structure. Studies using transgenic and gene ablation strategies revealed that both are tightly involved in bone homeostasis and senescence induction, rendering them attractive targets for the treatment of age-related diseases. BMI1 and LSH are important regulators of fail-safe programs such as replicative senescence, which lower the risk of tumor development. Moreover they are also regulators of osteogenic differentiation and bone formation in vitro and in vivo. In our proposal we follow the working hypothesis that chromatin modulators like BMI1 and LSH can be targeted for regenerative therapy of aging tissues without impairing important cell cylcle control mechanisms for the avoidance of tumor development. This project sets out to characterize this therapeutic potential by means of targeting BMI1 and LSH directly or downstream pathways without altering control of tumorigenesis. This segment of research is of extraordinary relevance with respect to in situ and ex vivo strategies of regeneration induction, tissue engineering and transplantation in the elderly. We expect new insight into principles of cellular aging and of degenerative diseases. We expect this project to be an excellent basis to expand our knowledge in this highly dynamic developing field in regenerative medicine in a grant-supported research network.