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Dr. Jonathan (Jony) Kipnis is a BJC Investigator and the Alan A. and Edith L. Wolff Distinguished Professor of Pathology and Immunology at Washington University School of Medicine in St. Louis. He is also Professor of Neurology, Neuroscience, and Neurosurgery and Director of the Brain Immunology and Glia Center there. He completed his BSc in Biology at Tel Aviv University, and he received his MSc in Neurobiology and PhD in Neuroimmunology from the Weizmann Institute of Science in Israel. Jony worked on the faculty at the University of Virginia for over a decade before joining the faculty at Washington University in St. Louis. He has received numerous awards and honors, including an NIH/NIA MERIT Award, the NIH Director’s Pioneer Award, the Harrison Foundation Distinguished Teaching Professorship in Neuroscience, a Gutenberg Research College fellowship from the Johannes Gutenberg University of Mainz, and the Distinguished Research Career Development Award from the University of Virginia. He is also a Member of the National Academy of Medicine. In this interview, Jony shares more about his life and science.
People Behind the Science Podcast Show Notes
Life Outside of Science (3:09)
When he’s not working, Jony loves to read a good book, enjoy a nice glass of wine, cook, and eat delicious food. He particularly has a passion for grilling.
The Scientific Side (5:18)
Jony is a neuroimmunologist. He works at the intersection of the immune system and the nervous system. The brain controls immune system activity, and the immune system affects brain function. The two work together to ensure our survival and well-being. Jony’s research is improving our understanding of how they interact when we’re healthy and in cases of nervous system damage or disease.
A Dose of Motivation (9:27)
One major source of motivation and inspiration for Jony is Thomas Jefferson. He has a whole book of quotes from Jefferson in his office. He is also inspired by Rita Levi-Montalcini and Carl Sagan, particularly their quotes below.
”I don’t believe that there would be any science at all without intuition.” – Rita Levi-Montalcini
“Somewhere, something incredible is waiting to be known.” – Carl Sagan
What Got You Hooked on Science? (12:07)
Jony grew up in a family of physicians. His father and grandmother were both medical doctors, and Jony’s family decided that he should become a doctor as well. When he played as a little kid, Jony pretended to be a doctor, but he always imagined he was discovering new medicines, rather than prescribing known medicines. One of Jony’s grandfather’s passed away from cancer at a relatively young age, and this sparked Jony’s interest in better understanding the disease. Not much was known about cancer at that time in the early 1980’s, and Jony decided to pursue studies in biology with the goal of doing cancer research and curing cancer. However, while in his graduate studies, Jony attended a lecture from a professor who was doing interesting research on the interactions between immune cells and brain cells, and he decided to try working in her lab. He quickly fell in love with the field of neuroimmunology and has continued doing research in this area since then.
The Low Points: Failures and Challenges (24:46)
It is incredibly common for experiments to fail and for your results not to match your original hypothesis. A large part of science is trying to troubleshoot, iterate, and ultimately (hopefully) get experiments to work. Jony had a student who had to close his project in his fifth year of graduate school because it just wasn’t working, and they couldn’t get consistent results. They realized later that the project wasn’t incorrect because another lab eventually showed results which were very similar, but stopping work on the project was really difficult for both Jony and the student to come to terms with.
Getting results that are different from what you expected also happens often in science. Jony had a postdoc share results from their project, and there were clear differences between the two groups. Jony was really excited, and congratulated the postdoc on his amazing work. When the postdoc pointed out that the results for the two groups were the opposite from what they expected, Jony was even more excited because this made the difference even more likely to be real. The next step was to replicate the work to ensure they got the same result and then try to understand what might be happening to get these results. Persistence and resilience are key to being successful in science and discovering new things.
A Shining Success! (33:03)
Shortly after finishing his graduate work, Jony had a wild idea that not having a functional immune system would negatively impact brain function. The lab he was working in wasn’t equipped to carry out the experiments for this study, so they collaborated with a lab at another institution to complete the project. They purposely didn’t give the investigator much information about the study because they wanted the experiments to be as unbiased as possible. They sent the investigator some animal models that were normal and some that did not have functional immune systems. The results showed that the individuals without a functional immune system had substantial cognitive problems, compared to those with a normal immune system. To confirm their findings that immune system function was critical for good brain function, they prepared two groups of animal models without functioning immune systems, and they gave one group back the immune cells they thought were involved. The individuals that were not given the immune cells back performed poorly, while those with the immune cells performed well on the tests. This was a really exciting finding and an amazing feeling.
Another memorable success happened in 2014 when a postdoc in Jony’s lab discovered lymphatic vessels in the brain. The lymphatic system is important for removing wastes from tissues, and it was long believed that there were no lymphatic vessels in the brain. The postdoc called Jony over to the microscope one day and showed him some vessels that clearly contained immune cells, even though all of the blood had been removed. They were surprised, and decided to investigate these unexpected vessels further. Jony asked a colleague for markers to label for lymphatic vessels to try prove that they weren’t lymphatic vessels. Once the markers were applied, it became clear that there were indeed lymphatic vessels in the brain. It was a true eureka moment.
Book Recommendations (3:42, 46:36)
In Praise of Imperfection: My Life and Work by Rita Levi-Montalcini, Advice to a Young Scientist by Peter Medawar
Most Treasured Travel (36:40)
Jony has had many opportunities to travel to wonderful places for science. He was born in the Republic of Georgia, which spans across Eastern Europe and West Asia. His family moved to Israel in 1990, and he had not been back to his home country since then. In 2017, there was a scientific meeting held in the Republic of Georgia, and it was really meaningful to go back to the country after 27 years away. While there, Jony resisted familiar sites and places he and his family used to go on summer vacation. He returned again in 2019 and has been going almost every year since then. The scientific meetings have been fantastic, and they have brought together great scientists from all over the world.
Quirky Traditions and Funny Memories (40:23)
When attending scientific conferences, it is a lot of fun to spend quality time with colleagues in the field. Jony’s lab recently attended the Society for Neuroscience meeting, which is one of the largest neuroscience conferences. He went out to dinner with a few colleagues, and they sat together for about three hours, having a great discussion and laughing almost non-stop. He laughed so much that the muscles in his face hurt the next day.
Also, in September, Jony participated in a conference called ReThink Neuroimmunology that was hosted by his university in St. Louis. There is a tight knit core of investigators who regularly attend this meeting each year, and they decided to take the group to a place called The City Museum. This is a quirky architectural playground where people of all ages can climb through tunnels, go down slides, explore caves, go on rides, and more. After a long day of discussions and a formal dinner, the group met up at The City Museum, and no one really knew what to expect. Jony came late after making sure everyone else had transportation to get there. When you walk in, there is a huge slide that brings people down to the entrance from a higher floor, and he had to laugh when he saw a respected scientist standing there barefoot trying to pull another scientist out of the slide by their leg because they had gotten stuck. The whole event was a fun and funny experience that highlighted the sense of humor of the group.
Advice For Us All (46:36)
Don’t listen to anyone else’s advice because what works for someone else won’t necessarily work for you. Follow your intuition, and listen to your own inner voice. If you’re not excited about the projects you are doing and the scientific questions you are asking, it will be very difficult to pursue a career in science, because there are so many failures and challenges you will have to face. Also, remember that it’s okay to make mistakes.
Guest Bio
The Kipnis lab is dedicated to unraveling the intricate interactions between the immune system and the central nervous system (CNS). It explores the cellular and molecular mechanisms that underpin these interactions across a spectrum of conditions, including neurodegenerative, neurodevelopmental, and mental disorders, as well as in physiological states like healthy aging. Jony and his colleagues discovered that brain function is partly reliant on the integrity and functionality of the immune system, with immune molecules (cytokines) playing neuromodulatory roles. The fascination with immunity and its role in neurophysiology is what brought the lab to a breakthrough discovery of meningeal lymphatic vessels that drain the CNS into the peripheral lymph nodes and thus serve as a physical connection between the brain and the immune system. This finding challenged the prevailing mechanisms underlying CNS “immune privilege” and opened new avenues to mechanistically study the nature of neuroimmune interactions under physiological and pathological conditions. The implications of this work are broad and range from autism to Alzheimer’s disease through neuroinflammatory conditions, such as Multiple Sclerosis.
Jony’s lab also identified the skull and vertebrae bone marrow niches as local immune reservoirs for the brain and spinal cord, whose role in neurological disorders is yet unknown. Recently, the lab unveiled new structures involved in waste removal from the brain, which are also utilized by immune cells for brain surveillance and during pathological neuroinflammation. Additionally, the team demonstrated that synchronized neuronal oscillations during sleep facilitate the movement of cerebrospinal fluid through the dense brain parenchyma. These discoveries not only elucidate the role of macroscopic brain waves during sleep but also offer novel insights that could lead to more effective treatments for neurodegenerative diseases. Earlier this year, the Kipnis lab also reported on engineered T cells that could be therapeutically used for neurodegenerative diseases. Outside of science, Jony spends his free time hanging out with his family, cooking and grilling, getting immersed in a good book, and enjoying and collecting good wine.
Support for this episode of People Behind the Science was provided by Innovative Research, Inc.