Decoding tissue regeneration

We investigate how tissue function is restored to maintain healthy life

Overview

We are interested in the fundamental biological principles of tissue maintenance and longevity. Our research centers on the mammalian liver, organ with an unparalleled regenerative capacity, to understand how cellular communication via molecular cues coordinate repair following injury. We specifically aim to decipher how ageing and chronic stress impair these regenerative mechanisms, leading to conditions such as fibrosis, acute liver failure and cancer. By mapping the molecular pathways maintaining liver homeostasis or causing age-associated decline, we strive to identify novel therapeutic targets for patients with hepatic diseases. We are based at the Institute of Biotechnology, an independent unit of the Helsinki Institute of Life Science (HiLIFE) within the University of Helsinki.

Research

We use synthetic biology, microscopy techniques and cutting edge molecular profiling to dissect the cell biology of regenerative processes.

Coordination of cell behaviour during Liver regeneration

How do tissues know when to stop? Liver has a remarkable capacity to regrow the lost tissue exactly matching the initial size . We seek to understand how the various cell types coordinate to restore tissue function post injury without losing the growth control?

Formation of Signalling Gradients

Secreted cytokines and growth factors are critical for regenerative growth and tissue patterning. Their effective range is dictated by the ability to travel in the extracellular space. This project investigates how extracellular proteoglycans control the movement of cytokines using synthetic biology and mathematical modelling.

Effect of regeneration on tissue health and longevity

Liver is able to regenerate without forming a scar tissue therefore maintaining its functionality throughout the life. However, chronic exposure to inflammatory signals can result in accumulation of fibrotic scar-like tissue and in the worst case liver failure. This project investigates the limits of regeneration and whether exposure to injury-associated signals cause long-lasting changes in hepatocyte function.

Investigating the onset of liver cancer

Majority of liver cancers are associated with inflammatory conditions driven by lifestyle factors or exposure to toxins and pathogens. We seek to understand the molecular mechanisms how inflammatory states shape hepatic tumor initiation and progression

PhD. Nalle Pentinmikko

We are hiring

Team members

Academy Research Fellow, Principal Investigator

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PhD Student

Publications

Cellular shape reinforces niche to stem cell signaling in the small intestine

Pentinmikko N., Lozano R., Scharaw S., Andersson S., Englung JI., Castillo-Azofeifa D., Gallagher A., Broberg M., Song KY., Sola-Carvajal A., Speidel AT., Sundstrom M., Allbritton N., Stevens MM., Klein OD., Teixeira A., Katajisto P.

doi:10.1126/sciadv.abm1847 Science Advances 2022

NOTUM from Apc-mutant cells biases clonal competition to initiate cancer

Flanagan DJ., Pentinmikko N., Luopajärvi K., Willis NJ., Gilroy K., Raven AP., Mcgarry L., Englund JI., Webb AT., Scharaw S., Nasreddin N., Hodder MC., Ridgway RA., Minnee E., Sphyris N., Gilchrist E., Najumudeen AK., Romagnolo B., Perret C., Williams AC., Clevers H., Nummela P., Lähde M., Alitalo K., Hietakangas V., Hedley A., Clark W., Nixon C., Kirschner K., Jones EY., Ristimäki A., Leedham SJ., Fish PV., Vincent JP., Katajisto P., Sansom OJ.

doi: 10.1038/s41586-021-03525-z Nature 2021

Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium

Pentinmikko N., Iqbal S., Mana M., Andersson S., Cognetta III A., Suciu R., Roper R., Luopajärvi K., Markelin E., Gopalakrishnan S., Smolander O-P., Naranjo S., Saarinen T., Juuti A., Pietiläinen K., Auvinen P., Ristimäki A., Gupta N., Tammela T., Jacks T., Sabatini DM., Cravatt BF., Yilmaz Ö., and Katajisto P.

doi: 10.1038/s41586-019-1383-0 Nature 2019

Full List of Publications

Opportunities

Current Lab Vacancies

We are looking for passionate doctoral candidates interested in stem cell biology and experimental hepatology. Apply here

Inquiries for an internship / Master's thesis work, email: nalle.e.pentinmikko [at] helsinki.fi