Antibodies and Aging Gracefully: Dr. Peter Pioli

Before we’re even born, our bodies begin to grow and train an army of spies and assassins, creating a crew of immune system fighters in the upper chest's thymus gland. While this production is dominated by T cells, other immune cells such as B cells and plasma cells can be generated within the thymus, albeit at a very low level.

 

After adolescence, the thymus reduces production at its 'spy and assassin' factory to a trickle. This has consequences because as we age, our immune system makes mistakes, leading to mutations in our DNA; changes in the types of antibodies we produce, and odd feedback loops.

 

Those glitches contribute to the generation of chronic lymphocytic leukemia or B-cell lymphomas such as non-Hodgkin lymphoma. They can also contribute to the development of autoimmune diseases such as lupus and myasthenia gravis.

 

"We think this all has to do with a life-or-death signalling loop," said Dr. Peter Pioli, who moved to the University of Saskatchewan last year to become an assistant professor of Biochemistry, Microbiology & Immunology. In February, he published his findings in iScience.

 

"For autoimmune patients, you get this thymus that gets filled up with all these B-cells and plasma cells, so you no longer have this little trickle; you have a bit of a runaway train," he said.

 

Using mouse models, Pioli and his team are trying to piece together the triggers convincing aging B-cells to mistakenly ramp up plasma cell production. They want to know how this impacts the development of various diseases.

 

In this episode, Pioli explains his interest in plasma cells.

 

"It  fascinates and confounds you all in one," said Pioli. "This one cell has to have this perfectly aligned machinery to do this. And it's kind of hard to look away when you find something like that."

 

A "curious troublemaker" who loved to tinker as a kid, Pioli remembers taking apart tools and objects in his parents' garage, removing pieces and trying to rebuild them. That curiosity carried him through his undergraduate, graduate studies and post-doctoral work in Wisconsin, Utah, and California.

 

"It's just a lot of fun," said Pioli. "You get the payoff of hopefully finding something that could actually help someone someday: understanding aging, understanding these breakdowns that lead to autoimmune diseases and tissue breakdown."

 

Pioli admits his scientific career has taken plenty of detours, but he's extremely grateful it unfolded the way it did.

 

"There's a lot you learn from that, not just in terms of experience," he said. "You also learn about yourself in terms of your potential to persevere.  And maybe the potential to be supremely stubborn, to keep at it."