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Universitätsklinikum Essen
Forschung & Lehre

Working Group

Dr. rer. nat. Laura Elisa Buitrago Molina, PhD

Medical Research Centre,
Gastro MFZ, 2nd Floor

In my research group, we have been dealing with the mechanism of autophagy for a long time. Autophagy is a natural process in which the cell degrades and recycles parts of itself. Under physiological conditions, autophagy takes place permanently at a low level in the cell. This is an important process for cell survival and the maintenance of homeostasis, i.e. it maintains balance by converting proteins into energy.

Autophagy is also involved in the removal of pathogens and apoptotic cells. Autophagy is therefore a survival mechanism, but it can also lead to cell death after prolonged deficiency conditions. The molecular mechanism of autophagic cell death has not yet been fully elucidated.

It is known that deregulation of autophagy is associated with various diseases, including tumors. Hepatology is one of the most attractive fields of research, because hepatocellular carcinoma is a frequent cause of death after chronic liver damage and causes almost 5% of all deaths worldwide due to tumours.

In our first projects, we have shown that the pharmacological inhibition of mTOR, an autophagy regulator, effectively inhibits the proliferation of hepatocytes in chronic liver damage. This effect is associated with the modulation of cell cycle-specific proteins in hepatocytes and the sustainment of apoptosis sensitivity. In addition, long-term mTOR inhibition significantly delays the development of liver tumors in mice caused by DNA damage [1].

In another study on the regulation of the cell cycle, we could show that the degree of liver damage and the strength of p21 activation have a strong effect on tumor development in the liver [2]. Mechanistically, this loss of p21 is compensated by activation of Sestrin2, impairment of mTOR signaling and activation of cytoprotective Nrf2 signaling [3].

In addition, we investigated the role of the proapoptotic protein BID in chronic liver damage and hepatocarcinogenesis. We were able to show that BID promotes the development of tumors. However, this function of BID is not related to an increased proliferation of liver cells or a disturbed reaction after DNA damage. In contrast, BID suppresses p38 activity and facilitates malignant transformation of hepatocytes [4].

Modulation of the immune system during liver damage and tumor development was also part of our studies. Lymphopenic mice exhibited significantly lower liver damage and tumor development despite increased mortality. We were able to show that CD8+ T cells and lymphotoxin-beta are central mediators of HCC formation. Depletion of CD8+ T cells and pharmacological inhibition of the lymphotoxin-beta receptor significantly delay tumor development in mice with chronic liver damage [5]. I received one of my two DFG grants (BU 2722/2-1) for research in this field.

However, the implementation of therapy approaches based on autophagy mechanisms after liver damage and hepatocellular carcinoma remains difficult. That is why we are less concerned with tumor diseases than with the role of autophagy in regeneration.

In one of the studies, we showed that the degree of liver damage and the strength of p21 activation also had an effect on liver regeneration [2]. Encouraged by this, we were able to show that the proliferation and regeneration capacity of hepatocytes with Atg7 deficiency is impaired. ATG7 is a central molecule in autophagy processes. This aspect is also considered particularly promising by the DFG and is funded accordingly (BU 2722/2-3).

Regeneration is an important topic in medicine and is closely linked to successes in transplantation. As the University Hospital Essen is the largest center for liver transplantation in Germany, this is the optimal environment for our research.

1. Buitrago-Molina LE, Pothiraju D, Lamlé J, et al. Rapamycin delays tumor development in murine livers by inhibiting proliferation of hepatocytes with DNA damage. Hepatology 2009;50:500-509.

2. Marhenke S, Buitrago-Molina LE, Endig J, et al. p21 promotes sustained liver regeneration and hepatocarcinogenesis in chronic cholestatic liver injury. Gut 2014;63:1501-1512.

3. Buitrago-Molina LE, Marhenke S, Longerich T, et al. The degree of liver injury determines the role of p21 in liver regeneration and hepatocarcinogenesis in mice. Hepatology 2013;58:1143-1152.

4. Orlik J, Schüngel S, Buitrago-Molina LE, et al. The BH3-only protein BID impairs the p38-mediated stress response and promotes hepatocarcinogenesis during chronic liver injury in mice. Hepatology 2015;62:816-828.

5. Endig J, Buitrago-Molina LE, Marhenke S, et al. Dual Role of the Adaptive Immune System in Liver Injury and Hepatocellular Carcinoma Development. Cancer Cell 2016;30:308-323.

Dr. rer. nat. Laura Elisa Buitrago Molina
AG Leitung

Dr. rer. nat. Laura Elisa Buitrago Molina

M.Sc. Genetik und Bioinformatik, Arbeitsgruppenleiterin

+49 201 723 6094 +49 201 723 6915 E-Mail schreiben Zum Steckbrief