Bichitra Paul

Name: Bichitra Paul

Nationality: Bangladeshi

Academic Background: Master of Science in International Master in Applied Ecology(Erasmus Mundus Joint Master Degree from University of Poitiers, France and University of Coimbra, Portugal). Bachelor of Science in Biochemistry and Molecular Biology from University of Dhaka, Bangladesh.

Project Title: The impact of essential fatty acids in the progression and development of Metabolic-Associated Fatty Liver Disease Hepatocellular Carcinoma

Project Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer type and the second most common cause of cancer-related death globally. Previously, the cause of HCC was attributed mainly to Hepatitis B virus, Hepatitis C virus and alcoholism, but recently cases related to Metabolic-associated fatty liver disease (MAFLD) are steadily increasing. This is due to the rise of obesity and “over-nutrition” in all countries, especially in the western world.
Metabolic rearrangements are a hallmark of liver cancers, and lipids among all metabolites are crucial because they play important roles in structural and biochemical processes in the body. Essential fatty acids (EFAs) linoleic acid (LA) and alpha-linolenic acid (ALA) are lipids which are precursors to many molecules in the body such as prostaglandins, thromboxane, ceramides, etc. These molecules then mediate many crucial processes in the body.
We have been able to demonstrate that LA levels were significantly lower in the serum of MAFLD-HCC patients compared to the tissues. In addition to that, the fatty acid transporter levels were higher in the tissues of these same patients. Hence, I hypothesise that MAFLD-HCC tumours are addicted to fatty acids, and that essential fatty acids have an important role in the development and progression of MAFLD-HCC.

Project Aim:  Firstly, I am characterising the metabolic fate of EFAs in hepatocytes and MAFLD-HCC cells by various functional assays. This is to establish the baseline conditions in our cell lines of interest with the treatment and depletion of EFA.  Then, I shall elucidating the molecular mechanism of EFA-mediated signalling by using high-throughput RNA-sequencing technology in order to define the genes deregulated by EFA treatment and depletion, which will be matched with measuring the levels of various metabolites of EFAs. This will be followed by further validation of the results in our mouse models as well as genome-edited cell lines.

Expected Outcome:  Results in this project will be of clinical importance for the treatment of MAFLD-HCC. This can be ensured because all experiments are in combination with data obtained from our patient cohort and tested in primary cell cultures as well as in mouse models. A combination of a variety of techniques will provide a robust outcome, elucidating how EFAs play an important role in the development and progression of MAFLD-HCC. This project will reveal new molecular mechanisms of MAFLD-HCC, defining the role of EFAs in the development and progression of this disease. This may be exploited for therapy in order to improve the quality of life of the steadily increasing number of MAFLD-HCC patients in Europe.

Contact:  bichitra.paul@bric.ku.dk