Episode 141: Jeff Iliff on newly discovered system that clears waste from the brain

Our guest today is Dr. Jeffery Iliff, a professor of psychiatry and behavioral sciences in the Department of Neurology at the University of Washington. Much of Jeff’s research focuses on neurodegeneration and traumatic brain injury. He is the associate director of research at the VA Puget Sound Health Care System and a co-leader for research at the University of Washington’s Alzheimer’s Disease Research Center. In this episode, we talk about Jeff’s investigations into the glymphatic system, which is a newly discovered brain-wide network of perivascular spaces that facilitates the clearance of waste products from the brain during sleep. Jeff goes on to describe how he is exploring how the glymphatic system fails in the aging brain as well as in younger brains after traumatic brain injury. Jeff and Dawn also have a conversation about their collaboration on a research project  that’s focused on how extreme stressors impact the glymphatic system. Together they are investigating a potential approach to optimizing glymphatic clearance for individuals with acute or chronic sleep deprivation. Show notes: [00:02:55] Dawn opens the interview asking Jeff where he grew up. [00:03:21] Dawn asks what Jeff what he was like as a kid. [00:04:01] Ken mentions that it wasn’t until Jeff was working as a lifeguard at a boy scout camp that he first became interested in science. Ken asks Jeff what it was about his lifeguard experience that triggered the interest. [00:05:06] Dawn asks what led Jeff to the University of Washington as an undergrad. [00:06:02] Ken mentions that Jeff originally intended on going into pre-med. Ken explains that Jeff changed his mind and asks about a suggestion from a girlfriend that caused Jeff to have a change of heart. [00:07:39] Dawn points out that in addition to working in the lab as an undergrad, Jeff also worked a 48-hour shift as an EMT over the weekends. Dawn asks Jeff why he kept such a busy schedule. [00:09:35] Ken asks what led Jeff to the Oregon Health & Science University for his Ph.D. [00:10:53] Dawn asks if it’s true that Jeff’s wife played a big role in his decision to travel across the country to New York for his post-doc at the University of Rochester. [00:13:06] Dawn mentions that after the second year of Jeff’s post-doc, he was promoted to a junior faculty position because he was part of the team that discovered a brain cleaning system known as the glymphatic system. The team published a paper in 2012 in science translational medicine that was the first of about ten papers that later became known as the “glymphatic papers.” After a follow-up paper in 2013, Science Magazine cited the discovery that the glymphatic system cleans the brain during sleep as one of the “Top 10 Breakthroughs of 2013.” Dawn asks what this experience was like for Jeff as a young post-doc and junior faculty member. [00:15:55] Dawn explains that the lymphatic system is a network of vessels extending throughout most of the body that transport excess fluid and waste from the interstitial spaces between cells to the blood. She goes on to explain that these vessels are notably not found in the brain leading to the question of how interstitial fluid is cleared in the brain. Jeff’s team discovered the glymphatic system, which serves the same function in the brain as the lymphatic system in the rest of the body. This discovery turned out to be a paradigm shift and led to numerous subsequent studies. Dawn asks Jeff how the initial 2012 study came about and how they identified a distinct clearing system in the brain that serves a lymphatic function. [00:19:59] Dawn mentions that after Jeff’s initial work in the glymphatic system, he went on to write what has become known as his sleep paper. Dawn goes on to say that for this study, Jeff used two-photon microscopy to visualize fluid moving in and out of the brain, and at some point, saw his tracer leaving the brain.