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Mechanobiology of cardiac regeneration – Elif Eroglu's Group

Adult heart is one of the least regenerative organs in the human body. My group studies aquatic salamanders that have a fascinating regenerative capacity to ask how heart function can be restored. We complement this with a human cardiac organoid model to evaluate the translational potential of candidate mechanisms and molecules.

Six people standing outside smiling for the kamera.

Our research

Adult heart is one of the least regenerative organs in the human body, with substantial fibrotic scarring in response to tissue damage. In contrast, aquatic salamanders, such as the newt, display unique heart regeneration capacities. Yet, we know little about the underlying physical principles of cell and tissue dynamics. To cover this knowledge gap, we are currently working towards achieving the following research goals:

Deciphering the role of tight junctions in heart regeneration

Tight junctions are traditionally known for their role in generating a permeability barrier for our tissues. Recently, it has been demonstrated by us and others that these junctions have important functions beyond controlling the paracellular transport. We previously identified an important role for tight junctions in mediating heart muscle regeneration. We now aim to understand how dynamic remodeling of tight junctions in epicardial cells (cells covering the heart) impacts epicardial cell migration, proliferation, and differentiation. 

Mechanics of heart regeneration

While we know much about biochemical signals orchestrating regeneration, we know little about biomechanical cues involved. We are engineering tools to allow intravital imaging of the regenerating salamander heart and combine force measurement techniques with imaging to ask how physical forces acting on heart cells change during regeneration. 

Enhancing the regenerative capacity of the human heart

We utilize human cardiac organoids as a platform to translate our findings in salamanders. Cardiac organoids also allow us to study the potential interaction between different organ systems such as the developing heart and the placenta (in collaboration with Qiaolin Deng’s Lab). 

How does it all end?

One of the most fascinating aspects of salamander regeneration is its precision. How do cells sense when the regeneration is complete and terminate regenerative programs in a timely manner? Our ERC funded project Tightly Controlled is looking into this question with the goal of identifying mechanisms that prevent loss of growth control.

Publications

Selected publications

  • Article: NATURE CELL BIOLOGY. 2022;24(5):659-671
    Poch CM; Foo KS; De Angelis MT; Jennbacken K; Santamaria G; Bähr A; Wang Q-D; Reiter F; Hornaschewitz N; Zawada D; Bozoglu T; My I; Meier A; Dorn T; Hege S; Lehtinen ML; Tsoi YL; Hovdal D; Hyllner J; Schwarz S; Sudhop S; Jurisch V; Sini M; Fellows MD; Cummings M; Clarke J; Baptista R; Eroglu E; Wolf E; Klymiuk N; Lu K; Tomasi R; Dendorfer A; Gaspari M; Parrotta E; Cuda G; Krane M; Sinnecker D; Hoppmann P; Kupatt C; Fritsche-Danielson R; Moretti A; Chien KR; Laugwitz K-L
  • Article: NATURE CELL BIOLOGY. 2022;24(5):645-658
    Eroglu E; Yen CYT; Tsoi Y-L; Witman N; Elewa A; Araus AJ; Wang H; Szattler T; Umeano CH; Sohlmer J; Goedel A; Simon A; Chien KR
  • Article: JCI INSIGHT. 2022;7(2):e152198
    Tang CSM; Mononen M; Lam W-Y; Jin SC; Zhuang X; Garcia-Barcelo M-M; Lin Q; Yang Y; Sahara M; Eroglu E; Chien KR; Hong H; Tam PKH; Gruber PJ
  • Article: NATURE COMMUNICATIONS. 2021;12(1):5126
    Yang R; Goedel A; Kang Y; Si C; Chu C; Zheng Y; Chen Z; Gruber PJ; Xiao Y; Zhou C; Witman N; Leung C-Y; Chen Y; Fu J; Ji W; Lanner F; Niu Y; Chien K
  • Article: CELL. 2014;156(6):1259-1273
    Eroglu E; Burkard TR; Jiang Y; Saini N; Homem CCF; Reichert H; Knoblich JA

Funding

Grants

  • ERC StG 2024
    European Research Council
  • KID Grant, Karolinska Institute
  • Wallenberg Academy Fellow 2023
    Knut och Alice Wallenbergs Stiftelse
  • Ã…ke Wibergs Stiftelse
  • Starting Grant
    Swedish Research Council
  • Ming Wai Lau Center Seed Grant

Staff and contact

Group leader

All members of the group