‘Unfortunately, fat has a rather bad reputation, especially cholesterol’

29 Jul 2020

Dr Johan Ericsson, HBKU. Image: HBKU

Dr Johan Ericsson of HBKU is working to identify new therapeutic targets for cardiometabolic disease.

After receiving his BSc and PhD focusing on the biochemistry of enzymes in cholesterol biosynthesis from Stockholm University, Dr Johan Ericsson went to the University of California-Los Angeles (UCLA) for postdoctoral work.

After six years there, he returned to Sweden to start a new research group at the Ludwig Institute for Cancer Research. A decade after that, he moved to Ireland to take up an SFI Stokes professorship at University College Dublin (UCD) where he started to explore the more general role of regulated protein degradation in lipid metabolism.

Deciding he wanted to return to the lab bench, Ericsson took up a position at Hamad Bin Khalifa University (HBKU) in Qatar in 2019.

What inspired you to become a researcher?

I think it was during my postdoctoral work at UCLA. I started to realise that I could predict how cells were going to respond to specific changes in their genome, which allowed me to design follow-up experiments even before I received the initial results.

The excitement and satisfaction of getting it right was quite addictive. This was something I missed at UCD, where I got further away from the frontline.

Can you tell us about the research you’re currently working on?

We are currently running two broad projects, one addressing the link between lipid metabolism and cell cycle progression, and the other exploring the regulation of the sterol regulatory-element binding protein (SREBP) pathway and its role in human disease.

Both projects have evolved over time and are based on our previous work. We performed a number of large molecular screenings to identify novel mechanisms that regulate SREBP-dependent lipid metabolism in Dublin, and we will now pursue some of the more promising hits from these screens in liver and fat cells derived from human stem cells.

The long-term goal of this project is to identify new therapeutic targets for cardiometabolic disease. Recent data indicates that lipid synthesis plays and important role in tumour cells. Thus, the fact that the SREBP pathway controls cell cycle progression and cell growth is very exciting.

In your opinion, why is your research important?

Disturbances in lipid metabolism are at the core of several major health issues facing modern society, including cardiovascular disease, obesity and type-2 diabetes (T2D). In fact, most of the developed world, including Qatar, is facing a cardiometabolic health crisis, with wide-ranging health, social and economic consequences.

For example, the incidence of T2D is very high in Qatar, approaching 20pc. Research in our group is focused on identifying new ways to control lipid metabolism, with a special focus on the SREBP family of transcription factors.

By controlling fatty acid and cholesterol metabolism, this family of proteins are intimately linked to T2D and cardiometabolic disease. For example, SREBP1c is activated by insulin signaling, and SREBP1c-dependent lipid synthesis contributes to the development of insulin resistance in T2D patients.

Thus, SREBP1c is a valid therapeutic target in these patients. The SREBP pathway is also a major target for cholesterol-lowering therapies in cardiovascular disease. Globally, more than 250m people take statins to reduce their low-density lipoprotein (LPL) cholesterol levels, and the cholesterol-lowering action of these drugs is dependent on the SREBP pathway. Thus, our work on the SREBP pathway is relevant to both T2D and cardiometabolic disease.

What are some of the biggest challenges you face as a researcher in your field?

Lipid metabolism has been studied in great detail in animal models and human cancer cell lines. However, because of the limited supply of healthy primary human cells, lipid metabolism has not been studied in great detail in non-transformed human cells and there is an urgent need to develop such cell models.

These types of models may become an important complement to animal and human/patient studies, and may prove especially valuable when translating observations made in animal models to a human setting and during drug development.

Are there any common misconceptions about this area of research?

We work in the area of lipid metabolism, ie fat metabolism. Unfortunately, fat has a rather bad reputation, especially cholesterol. Clearly, excessive fat is associated with serious human diseases, including obesity, cardiovascular disease and T2D.

However, fat is absolutely essential for all living organisms. All cells, from the simplest bacteria to human neurons, are surrounded by a lipid membrane, which protects them from the environment.

Fat is also a vital energy resource in many higher organisms. Cholesterol plays a number of important roles, not least as a substrate for the synthesis of vitamins, hormones and bile acids.

What are some of the areas of research you’d like to see tackled in the years ahead?

The current SARS-CoV2 (novel coronavirus) pandemic illustrates how vulnerable we are to these types of events. People with certain underlying medical conditions, including obesity, cardiovascular disease, T2D and cancer are at higher risk of developing serious complications following infection.

Thus, by reducing the incidence of these diseases in the population we may be better prepared for future pandemics. Clearly, we also need to tackle global food and energy security, as well as environmental protection.

Are you a researcher with an interesting project to share? Let us know by emailing editorial@siliconrepublic.com with the subject line ‘Science Uncovered’.