Tissue Damage Responses in Regeneration and Aging
Dr. Mikolaj Ogrodnik received his PhD at the Newcastle Institute for Ageing (Newcastle upon Tyne, UK) and did his post-doctoral research at the Mayo Clinic (Rochester, MN, US). His pre- and post-doctoral research was focused primarily on the relationship between cellular senescence and organ function in ageing and obesity. Ogrodnik’s laboratory explores a wide range of subjects including:
Mapping and controlling cell fates in injuries
This research aims to understand the spatiotemporal regulation of the skin’s response to wounding and the mechanisms by which cells transition from injury to healing. The hypothesis is that cells respond to injury on three levels: activating signaling pathways, altering transcriptional profiles, and changing ribosome composition. These mechanisms lock cells into states like senescence, proliferation, differentiation or death. With this project we aim to understand the crosstalk between molecular and cellular changes upon injury in situ and develop timely interventions that alter signaling pathways and alter cell fate to improve healing outcomes.
Treating trauma-driven frailty in elderly using anti-senescence interventions
Clinical data shows elderly individuals experience delayed healing, long-term complications, and higher mortality after injury. However, the mechanisms behind these differences are not well understood, and treatment options remain limited. This research project applies findings on senescence in aging and wounding to address trauma-induced frailty. Preliminary results suggest aged animals exhibit increased frailty and systemic inflammation after injury, likely driven by accumulating senescent cells. The study will explore the role of senescent cells in local and systemic inflammation and frailty by applying targeted anti-senescence treatments. Circulatory factors responsible for senescence-related frailty will also be characterized. Overall, with this project, we aim to establish what characteristics of aged organs are responsible for exacerbated frailty of elderly and find new treatment options against it.
Advancing understanding of rapid responses to tissue damage for enabling regeneration
Some animals such as axolotls can regenerate tissues after severe injury, while most mammals, including mice, show limited regenerative ability, leading to scarring. However, under specific conditions, regeneration is possible in mammals. This research aims to uncover differences in tissue responses that influence regenerative potential by comparing regenerative and non-regenerative models. The focus is on phenotypes like re-epithelialization, skin contraction, and molecular signaling (e.g., p-rpS6 induction, Erk signaling). By identifying differences between regenerative and non-regenerative conditions, the study seeks to enable improved tissue regeneration.
Improving grafting capacity of artificial human skin
Tissue-engineered skin aims to model human physiology, reduce reliance on traditional models, and develop skin transplants for wounds and burns. Two key insights drive this research: artificial skin is more physiologically accurate when vascularized, and in vitro skin shares similarities with wounded skin. Our team has developed a vascularized human skin model (VascuSKIN) and aims to refine it by adjusting conditions for optimal perfusion and in vivo-like characteristics. The next step is to develop two versions of artificial skin: one resembling a wound-like state and another with a more stable, homeostatic profile. These variants will be tested for their ability to integrate with host tissue in pre-clinical settings.
Selected Publications
Ogrodnik M, Carlos Acosta J, Adams PD, d’Adda di Fagagna F, Baker DJ, Bishop CL, Chandra T, Collado M, Gil J, Gorgoulis V, Gruber F, Hara E, Jansen-Dürr P, Jurk D, Khosla S, Kirkland JL, Krizhanovsky V, Minamino T, Niedernhofer LJ, Passos JF, Ring NAR, Redl H, Robbins PD, Rodier F, Scharffetter-Kochanek K, Sedivy JM, Sikora E, Witwer K, von Zglinicki T, Yun MH, Grillari J, Demaria M (2024). Guidelines for minimal information on cellular senescence experimentation in vivo. Cell. 2024 Aug 8;187(16):4150-4175.
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Ogrodnik M, Gladyshev VN (2023). The meaning of adaptation in aging: insights from cellular senescence, epigenetic clocks and stem cell alterations. Nat Aging. 2023 Jul;3(7):766-775.
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Ring NAR, Dworak H, Bachmann B, Schädl B, Valdivieso K, Rozmaric T, Heimel P, Fischer I, Klinaki E, Gutasi A, Schuetzenberger K, Leinfellner G, Ferguson J, Drechsler S, Mildner M, Schosserer M, Slezak P, Meyuhas O, Gruber F, Grillari J, Redl H, Ogrodnik M (2023). The p-rpS6-zone delineates wounding responses and the healing process. Dev Cell. 2023 Jun 5;58(11):981-992.e6.
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Ring NAR, Valdivieso K, Grillari J, Redl H, Ogrodnik M (2022). The role of senescence in cellular plasticity: Lessons from regeneration and development and implications for age-related diseases. Dev Cell. 2022 May 9;57(9):1083-1101.
(free PDF)