Next Generation of Scientists

Isabel Graupera

Visiting Scientist - Barcelona, Spain

Q. How did you decide to pursue a career in research?

As a medical doctor, the first time you are in front of a patient you realize there are a lot of things you don’t know, and patients challenge you with different problems all the time. It was my recognition of this lack of knowledge that pushed me to engage in research as a way to answer some of the questions raised daily in my clinical practice. During my specialization training I had the opportunity to join the research group in my hospital studying the complications of cirrhosis – then I fell in love with research. I started in a clinical research group and then moved to translational/basic research. Research is a difficult path. Frequently, we don’t have positive results and all the work from weeks/months seem useless, but it’s fun as well, and the scientific discussions are really interesting and lead to new questions every time. Furthermore, when the results of a research project lead to a change in patient treatment practices, this opportunity to improve patient care is priceless. I would say that it ultimately is the potential benefits for our patients that made me pursue a career in research.

Q. Have you encountered particular hurdles, challenges, or barriers along the way?

A research career offers endless challenges and the best conditions for success are a good mentor, a generous team to work with hand-in-hand, and sufficient funding. I have been very fortunate to have two of the best mentors and an amazing team with which to work. The challenge commenced for me when I started my own research group and tried to get funding for our research. As an MD, PhD, it has also been challenging to combine my clinical practice with lab research. With that being said, it has also been an extraordinary privilege to be able to work directly with patients and apply first-hand clinical experience to research practices.

Q. What attracted you to join the Hotamışlıgil lab at the Sabri Ülker Center?

I’m a hepatologist focused on the study of non-alcoholic fatty liver disease (NAFLD), one of the most prevalent liver diseases worldwide with a prevalence rising parallel to the epidemics of obesity and diabetes. The complex pathophysiology of NAFLD is not completely known but several studies point towards an important role of adipose tissue in the development and progression of NAFLD. That is why I first became attracted to the Hotamışlıgil lab, because this lab was the first to describe the inflammatory role of adipose tissue in metabolic diseases and to describe the meta-inflammation concept. The role of the liver in metabolic disturbances in obesity is gaining interest nowadays, and therefore joining the Center and the Hotamışlıgil lab offered me an amazing opportunity to learn about metabolism and inflammation and apply this knowledge to NAFLD.

Q. What particular scientific questions motivate you?

Although obesity and NAFLD are intimately linked, not all patients with obesity present NAFLD and not all NAFLD patients progress to advanced chronic liver disease and cirrhosis. Furthermore, the progression of NAFLD to cirrhosis is done at different velocities according to individual susceptibilities and also to different metabolic environments. These are the main questions presented by patients in clinical practice. In this context, because obesity is associated with the presence of a low-sterile inflammatory state, I’m most interested in understanding the role of innate immune cells in NAFLD development and progression. Are adipose tissue macrophages driving NAFLD progression through adipose-tissue-liver signaling? Are liver macrophages, under a deleterious metabolic environment, driving disease progression? Can we change the phenotype of macrophages to a more anti-inflammatory or pro-resolutive phenotype to halt NAFLD progression?

Shijun Deng

Postdoctoral Fellow

Q. How did you decide to pursue a career in research?

Actually, I had never thought that I would be a scientist when I was a child. However, when I came to choose a major after high school, I somehow found myself naturally pulled into the biological sciences. My initial exposure to scientific research was as a graduate student in the lab of Professor Christopher Elliot at the Queen’s University Belfast in Northern Ireland, UK. As is often the case, my interest to be a scientist grew as my original project rapidly evolved into exciting directions. But I was not sure I wanted to pursue a career in research until I graduated with a PhD degree from the University of Alberta in Canada.

Q. Have you encountered particular hurdles, challenges, or barriers along the way?

I started to study abroad in 2011. This is my tenth year away from home and family. Last year’s pandemic made it even more difficult for me to return home. I guess my parents will have to wait longer. But, I am very grateful for their support of my career. Speaking of research, I believe that pursuing a career as a scientist is full of challenges simply by virtue of the unpredictable nature of working with experiments. Most of the time, I found my hypothesis was wrong and I had to accept it and move on to do the next series of experiments. I have gotten used to it. Our lab always emphasized how important it is to learn how to enjoy these mistakes, as they take us to new paths of discovery.

Q. What attracted you to join the Hotamışlıgil lab at the Sabri Ülker Center?

I had heard of Dr. Hotamışlıgil as one of the world’s leading experts in metabolism and inflammation. My first encounter with his lab was a paper published in the journal, Cell, entitled ‘Nrf1 is an ER Membrane Sensor that is central to Cholesterol Homeostasis’. I was very impressed by the scientific rigor of this research done in the lab and the range of experimental approaches and the elegance of how molecular mechanisms were linked to physiology. As a scientist passionate about the study of cholesterol, I reached out to the authors and Dr. Hotamışlıgil, who patiently answered all of my questions in detail. Then I started to email former lab members to inquire about their experiences. All of them highly recommended the Center and Hotamışlıgil lab as an excellent place to perform cutting-edge research on metabolism. Then it became an easy decision for me to join the group.

Q. What particular scientific questions motivate you?

Atherosclerosis and associated cardiovascular disease are a major global heath burden, accounting for over 30% of global mortalities. My goal is to understand how cholesterol metabolism and inflammation interact in atherosclerosis, and how the understanding of these interactions can be useful in designing therapeutic strategies. Specifically, my research focus is investigating the role of macrophage Nrf1 in atherosclerosis. Understanding the function and mechanism of macrophage Nrf1 will provide important insights into a novel mechanism of immune-metabolic regulation in atherosclerosis and reveal a potential therapeutic target for the treatment of atherosclerosis.