A small protein yet to be discovered: PCSK9 and the hepatic receptor for glucagon. Face to face with Stefano Spolitu

Italian by origin, New Yorker by adoption. Inside the Columba University for an important research on the regulatory mechanism of a particular protein: PCSK9. What is it about?

PCSK9 protein expression detected by western blot

The diabetes mellitus (DM) is one of the most widespread diseases in the world affecting about 8.5% of the adult population and whose trend in the last decades has shown a progressive increase in incidence and prevalence.

Several Italian researchers, over the years, have been dealing with what can be considered a scourge of our century. Among them Stefano Spolitu, born in 1984, who just didn't want to refrain his activity. Master's Degree in Biological Sciences at theUniversity of Cagliari, PhD in Experimental Medicine and Therapy at theUniversity of Turin and a year as a foreign student in the city that never sleeps: New York. And just during this year, Stefano realized that for a city like New York, capable of making you feel part of something big and beautiful, he could have left his beloved Cagliari.

In 2016 Stefano returned to the big apple, joining one of the most prestigious universities in the world: the Columbia University at the Lale Ozcan Lab , Department of Medicine.

Dr. Stefano Spolitu

Stefano, why New York?

Like all Italian people of the 80s and 90s, I grew up with the myth of the big apple. I saw it in the movies, I dreamed of living it. But what triggered something inside me was the events of September 11, 2001. I was 17 years old at the time and something inside of me has changed.

How was the transition from a small reality like Cagliari to a laboratory in one of the most competitive universities in the world?

At the beginning it was shocking for various reasons: the language, the size of the city, the pressure that Columbia was a very competitive reality. However, I was lucky enough to meet some fantastic people, very competent but at the same time humble and ready to help you in case of troubles.

Columbia University

What was the research topic?

My research has focused on the regulatory mechanism of a particular protein, PCSK9, which role in LDL cholesterol metabolism is well known, but little is known about its intracellular regulation. We used gene silencing techniques in the animal model that allowed us to investigate how glucagon (a key hormone in glucose regulation and present in high concentrations in diabetic patients) was involved in the regulation of plasma levels of PCSK9. 

The topic is certainly very timely. How can we summarize the results you have achieved?

Glucagon, through its receptor, activates two signaling molecules, Epac2 / Rap1a, which promote the intracellular degradation of PCSK9. Considering a possible therapeutic use, activating these two molecules could lead to a decrease in PCSK9 levels and facilitate a lowering of LDL cholestorol levels. This would lead to an improvement in the metabolic status in different categories of patients, including those with diabetes.

What were the main difficulties you faced during your journey?

The distance from the family has often played an important role, especially in periods when the project had to be carried out “No matter what”. 

Not only difficulties but also a lot of satisfactions ... we have heard about prizes ...

In 2017, thanks to the support of my mentor, I won a fellowship offered by the American Heart Association which allowed me to continue my research project for 4 years. In 2019, my presentation at the annual retreat at the Institute of Human Nutrition was awarded the "Marija Chouinard Award for outstanding research presentation" and my name is now engraved together with the winners of past years, in the Great Hall of the Columbia University main campus.

What do you recommend to colleagues entering the world of research in this field?

I advise them to approach this world with clear ideas, to be ready for many sacrifices and to let themselves be guided by passion, because only in this way can it become a true "training ground for life".

Thanks a lot, Stefano. Good luck for your future!


Please enter your comment!
Please enter your name here