Only about a decade ago did scientists discover the immense potential of leveraging the immune system to combat neurodegenerative diseases. Professor of Neuroscience John Lukens played an integral part in that movement, and he continues to push the field forward today as the inaugural director of UVA’s Harrison Family Translational Research Center in Alzheimer’s and Neurodegenerative Diseases.
- Transcript
- 0:09
welcome to who's in STEM I'm Ken Ono your host and the STEM adviser to the provost and the Marvin Rosen Blum 0:15Professor of Mathematics at UVA Our goal is to evoke flights of imagination and 0:21wonder by showcasing the cornucopia of all that is STEM at UVA The marvelous 0:27world of UVA science technology engineering and 0:32mathematics Now I can't believe it This is our 33rd episode We definitely didn't 0:39know what we were doing when we started but I hope you would agree that we've kind of gotten the hang of it But in our 0:46first few episodes we had a news segment called Who's making discoveries I keep 0:53my pulse on all things STEM at UVA and I thought at the time when we were just beginning this show I thought it would 1:00be a good idea to share timely stories Now in 2023 we had an episode with Francis 1:08Collins the UVA alum who went on to direct the Human Genome Project and he 1:14actually by the way won the National Medal of Science In addition to my conversation with Francis we opened with 1:22the following fun snippet from the news segment Who's Making Discoveries Please 1:29enjoy As a spin on March Madness a UVA Health Discovery has advanced to the 1:34Elite 8 in Stat Madness an online tournament that crowns 1:39a significant biomedical achievement The UVA discovery competing for the title is 1:44from the John Lucans lab They've uncovered a molecule called a kenase that's responsible for orchestrating 1:51immune responses in Alzheimer's and multiple sclerosis This finding sheds light on the toxic buildup of plaque in 1:58the brain that causes memory loss Now that was just over one year ago and 2:03since then John Lukans has certainly continued to innovate John is UVA's Harrison Distinguished 2:11Teaching Professor of Neuroscience and he is an affiliate faculty member of the 2:16Center for Brain Immunology and GIA This past spring he was named the inaugural 2:22director of the Harrison Family Translational Research Center on Alzheimer's and Neurodeenerative 2:30Diseases Now that's a mouthful but it is a position and a charge that speaks to 2:36all of us And as the conversation goes on I'm sure I'll tell you about why it matters so much to me But John wow when 2:44it rains it pours Welcome to Who's in STEM Thanks It's great to be here So John we have a lot of very serious 2:51topics to talk about Let's just dive in I've had the opportunity to showcase UVA 2:57STEM science stuff that's at the forefront of research in many different directions And certainly we've 3:05highlighted UVA research in the direction of Alzheimer's and neurodeenerative diseases That's a big 3:10thing here at UVA It's one of our grand challenges So in an earlier episode I 3:15had a conversation with Dr Jadeep Kapoor and Dr Sarah Cusinis who co-lead UVA's 3:22brain institute I've also had the pleasure of having renowned cell biologist Dr George Bloom as a guest as 3:30well And all three of them and now you my fourth guest in the field think very 3:35deeply about the brain But before I get into your work in detail and the 3:41institute you founded refresh our memory What do we mean when we're talking about 3:46neurodeenerative diseases so uh neurodeenerative diseases is just a broad term to describe a cohort of 3:53diseases that are associated with the death of neurons So neurons control our 3:59basic movements our our senses they they help store our memories So when you have 4:04loss of them in certain areas of the brain you can have different phenotypes So you could have your loss of memory or 4:10you could have impaired movement So in loss of memory you're looking at things like Alzheimer's disease and loss of 4:16movement uh you're looking at things like ALS And um there are many common 4:21themes across uh neurodeenerative diseases Um one is the buildup of 4:27neurotoxic material in the brain as we age And this causes an inflammatory 4:33response and also cell death And this seems to be a major culprit uh that could be targeted translationally to 4:40find cures for these disorders And it's a really important issue of our time Unfortunately we really don't at the 4:47moment have disease modifying treatments for the vast majority of these neurogenerative diseases which are 4:54greatly on the rise It's an exciting time to be involved in this research Um and there's a great opportunity to make 5:00a huge difference So some of these buildups they're in the air everywhere and people talk about the amaloid 5:05plaques right that buildup Maybe you could talk a little bit more about that For example I know it's very difficult 5:11to even diagnose some of these neurodeenerative diseases So when one studies neurodeenerative diseases as a 5:18broad category what's involved in all of that yeah So it is a good point and that's one of the major hurdles that we 5:24have at the moment is early diagnosis Typically people are are presenting 5:29pretty far along in the disorder So with some primary memory issues or issues 5:35controlling movement So one of the big hurdles that we're going to face is identifying biomarkers that will enable 5:42us to modify the the course of the disease and and there's been some movement there um in in terms of 5:49combining proteomics and genomics and precision medicine to identifying combinations of things like amaloid beta 5:56tow and also uh synaptic damage markers in the CSF and in the blood And so we're 6:01getting closer to to having real biomarkers that could enable us to get in that very critical window to help But 6:08if you're a patient or as we sit here today you couldn't look at me and say you're 10 years into a neurodeenerative 6:15disease but I could be Yeah And it can come on super quick too I mean we're seeing it with some of infections in 6:20older people and also uh falls where everything's fine and then a month or a 6:26couple weeks after a fall or kind of a viral infection see people really turn a 6:31corner for the worse So it's it's um it can progress slowly over time or it can come on pretty quickly Do you think 6:37there's a threshold beyond which if there's sufficient cell death or cell failure I mean is it redundancy built 6:43into the brain that protects us for a period of time as these diseases progress yeah the the brain is I mean 6:50this sounds like an overstatement but it's amazing in terms of its plasticity um and how different areas of the brain 6:56can take over when there's loss in certain areas So it it's kind of amazing uh the plasticity that can be 7:03accomplished not just in neurodeenerative disease but in things like addiction and pain you can rewire 7:08and there is an opportunity even if there is a lot of loss to to still regain uh some some functioning that 7:16that's missing So for example there's individuals that have had issues with 7:22very serious depression and anxiety that was pretty much treatment resistant and 7:29you know really didn't have hope for some of these individuals and and through various uh processes of of 7:35cognitive therapy and others and you know retraining some brain networks we're seeing some improvement The same 7:41thing can be said for PTSD where there are these really large changes in in 7:46terms of personality and and and mood and the brain does have the capacity to 7:51rewire and and you can make an impact in that regard So I can add some personal experience but about 15 years ago my 7:59wife had a major seizure at night It was the last day of school for the kids We 8:05had just come back from a neighborhood party when my wife had the seizure Four hours later we're at the hospital at the 8:12university uh medical center and I was sitting down with a neurosurgeon who 8:18broke this news to me He says "Your wife has a brain tumor but the initial scan 8:23suggests that it's not the most dangerous kind It's not a glyobblastoma but a menioma which has very good 8:29margins meaning that there was the prospect that you could excise it and recover and have a completely normal 8:35life which is what happened But with regard to the plasticity I really want to share this story because it's a 8:41testament to the moment when I realized how amazing the human brain is Within the period of 48 hours we went from last 8:48day of school party to my wife's having brain surgery and they removed this golf 8:53balliz mass which turned out to be in a very convenient location And two days 8:59later my wife can't write she can't talk she's like not there And I remember 9:04meeting with the neurosurgeon thinking "My future is it's it's changed overnight." He said "Don't worry about 9:10this This is the MRI What you see is this cavity in the brain This time next 9:15week it will have closed up And over the course of the next couple of weeks 9:21you'll discover that well maybe next week Erica will learn how to take a step over a shoe box And maybe 10 days from 9:29now she can walk up a flight of stairs." And believe it or not if everything goes 9:34well she can go back to work in 6 weeks And it actually all happened And we were 9:40able to watch the progress because of MRI technology I have those photos where 9:46cavity slowly closes up And whatever happens the human brain had this amazing 9:53ability to reconnect She couldn't remember her name then she could remember it She couldn't write her 9:59signature and then she could And that was really kind of an amazing experience 10:04So degenerative diseases come in many forms right the the ones that I think we tend to be most afraid of include things 10:13that lead to cognitive decline and then like cancer How would you compare cancer 10:18and how cancer progresses in a patient and on the other hand neurodeenerative 10:23diseases which are quite insidious right yeah there's an interesting comparison there It's a lot of times there are 10:30overlaps in terms of at least in terms of how the immune system can be leveraged to to treat them The brain has 10:37developed ways to limit immune activation and that's what makes glyobblasto so difficult to treat Um it 10:44does have this partially controlled setting where it limits interaction with 10:50the immune system The interesting thing is there like for cancer treatments of the brains we're trying to boost immune 10:57activation whereas in many neurogenerative diseases we're trying to dampen down some of that activation so 11:03there isn't so much collateral damage So interestingly many of these pathways are shared between the two Um so you can 11:11think of ways modulators that would both inhibit and also turn down by kind of 11:16studying the same kind of pathways or cell types I want to circle back to one 11:21of the main reasons we're here today Congratulations You're the founding director of the Harrison Center Tell us 11:27about that What are the neurodeenerative diseases that you want to study and how's the work going thanks It's a it's 11:32a real honor to be leading this new effort It's it's uh desperately needed 11:38in the space of biomedical research and it's just a you know it's a real privilege to be in this position Uh it's 11:44it's going well It's been a couple weeks Um we're super excited for the new building Uh that's that's what we're 11:50working towards Uh we have a couple assistant professor faculty jobs out there What are you searching for so 11:56we're really looking for an interdisiplinary team We want expertise in cell death 12:02inflammation neuronal connectivity micro GA you know having this formed team with 12:09expertise in different areas And that's really worked out well for us um at UVA in the sense that we always have these 12:14checks and balances because you can't completely understand every facet of of 12:20the disease And so it helps to have different viewpoints and different expertise whether it's at cellular level 12:27or at the um the the circuit level hoping to to bring together an 12:33innovative group of people that just want to think outside the box to develop new treatments And it's been really cool 12:40interacting with with Evan Scott and hearing his vision and how the the two new centers between Nanostar and S could 12:47interface is just exciting in terms of the possibilities um and leveraging their technology to uh 12:54identify and go after some of the the molecules and cell types that that we're discovering There's been some incredible 13:00discoveries here at UVA over the last couple years and to have you know medicinal and nano technology in the 13:09same building to to really jumpstart those treatments and and discoveries of 13:15of new compounds and and ways to to to modify those pathways This is just going 13:20to be awesome So this team that you're assembling John you mentioned that you want to bring together researchers that 13:27have different kinds of expertise that you can bring to bear As the founding director what's your expertise it's 13:33funny enough um I'm an immunologist by training So I I received my PhD from UVA 13:39At the time I was studying uh TE-C cells and how they help eliminate viruses from 13:45the liver That was my start in science So I worked for Young Han in the Carter Immunology Center here at UVA She's 13:52she's still here and a big supporter of of me and our family Yeah It was interesting at the time because we were 13:57trying to basically rejuvenate immune responses and at the time there was this 14:03idea of of TE-C cell exhaustion Yeah So TE-C cells are the the cells uh that are 14:10activated to help eliminate uh cancer cells and virally and uh bacterally 14:16infected cells Um so they come in multiple flavors They're kind of the killer cells So they they say there's a 14:22tumor antigen there's a viral antigen in that cell we're gonna lock and load and and hit it But what happens over time is 14:29the cells become functionally exhausted So they still know that there's that virus or that tumor in that cell but 14:37they lose kind of the the payload and they become functionally exhausted So um 14:42this was thought to be a major driver of of cancer development um and progression 14:48And so we and others uh were trying to figure out ways how we could boost or 14:53rejuvenate those those te- cell responses And it it was really cool because it was only a couple decades ago 15:00uh that you know this idea of cancer immunotherapy was born Um and now 15:06there's multiple drugs that hit these pathways these checkpoint inhibitors uh that that are saving people's lives So 15:13and at the time it was kind of a crazy idea that was didn't have that much 15:19support behind but uh to see it blossom and it's something that I always kind of talk about when I'm teaching in the 15:25classes especially in the nerve imunology classes that I teach in you know we're at this early stage where 15:31we've we've recognized the importance of immunology but we really haven't tested 15:37uh the how efficient it could be to to target the immune system neurological disease and and just even though like 15:44you know I was only a small part of the cancer immunology checkpoint inhibitor that was the rush that got me to where I 15:51am today and it can happen in in your lifetime and if this takes a lot of energy and effort and uh enthusiasm to 15:59want to make a difference and it it definitely can happen Your career started here at UVA as you just 16:05described as an immunologist studying tea cells Uh I'm not a biologist but I 16:10don't think it takes much to recognize that you founding a institute to study 16:16neurodeenerative diseases sounds like wearing a different hat So something must have happened along the way So you 16:22you talked about how the idea that one can combat and and treat cancer by 16:30assisting the immune system I'm guessing that in your research as an immunologist you carried a little bit further How 16:36does that work yeah So after I was at UVA my wife and I moved to Memphis to 16:41work at St Jude Children's Hospital So St Jude is uh the famous children's 16:46hospital that treats catastrophic children's cancers but in addition uh 16:51rare genetic disorders and also infectious disease and it it was just an incredible place to be for for six years 16:58during my posttock You know one of the things there was don't just do science to do something 17:04incremental but do it to make a huge difference And it's it's kind of cool I was there you know at the 50-year 17:11anniversary and we had this huge reflection um and period like okay like 17:16when we opened what was the survival rates of of this you know tumor in children and what was discovery that 17:23changed that number and I think if you are creative and you think outside the box and you target multiple different 17:29systems you can make a real impact on some of these disorders So when I was there I started working on multiple 17:35sclerosis Um so multiple scerosis is a immune mediated neurological disease Um 17:41and it's been one of the success stories U it's not a perfect success by any means but one of the success stories 17:48that we have in terms of treatment of neurological neurogenerative diseases in that since it is an autoimmune disease 17:55there was early buy in to target the immune system and we have multiple treatments that really slow the 18:02progression and enhance the quality of life of multiple sclerosis patients Um 18:07and we don't have a cure yet but we're moving a lot closer to that And that 18:13experience of of seeing how the immune system could alter the brain in the context of multiposis caused me to to really figure 18:20out like okay the great thing about being an academic research is you know you can follow your passions and your 18:26ideas and it was looking at what was coming online at least from some of the genetic studies and some of the imaging 18:33it was clear that the immune system was involved in everything in the brain but there was very little real deep dive 18:40into how that was potentially contributing So I saw that as like a real opportunity to to dive in and kind 18:45of take my immune background and put it towards uh understanding neurological 18:50diseases So if I remember correctly about 10 years ago there was a huge 18:57discovery here at the University of Virginia I know because as STEM adviser I've been curating a list of major 19:03scientific discoveries I think you probably know where I'm going with this Science magazine which is one of the 19:08most prestigious journals in science Uh I believe it was 2015 correct me if I'm 19:14wrong but I think in 2015 there was a major result coming out of the University of Virginia that science 19:19called the breakthrough of the year Tell us about that and how you ended up being 19:25part of this revolution That discovery was made by the great Yonyi Kipniss who was uh a major reason that I was brought 19:32to UVA and is still a huge supporter of me and others It was an incredible 19:38discovery Uh and Yoni is you know he took a chance on a lot of us you know 19:43bringing in an immunologist to a neuroscience department But that's just kind of how he thinks Basically the 19:48discovery was that the brain has uh lymphatic vessels uh that are above the 19:54brain and just below the skull The paradigm until 10 years ago was that the brain didn't have lymphatics and this 20:00limited the interaction between the brain and the immune system and uh what Yonyi discovered and his team is right 20:07below the skull in this very thin layer there were lymphatic vessels and most uh 20:12people were missing it because when they do autopsies they they peel off the skull and they pull the brain out but 20:18when they're peeling off the skull they're also pretty much mangling the meningis and losing the lymphatics and 20:24he identified this and it was a it was a massive discovery because it would helped to break down the the the the 20:31separation between the immune system and the brain And since then we've come to know uh through our work that this 20:38lymphatic uh drainage pathway is really important in protecting the brain from traumatic brain injury And when it 20:43doesn't work as well it can lead to things like talopathies uh post uh traumatic brain injury And that's one of 20:50the projects that we're about to to publish um very soon It's amazing how 20:55quickly that that field's taken off since that initial discovery And we've we've come to know that these uh 21:01lymphatic drainage uh vessels are really important in terms of eliminating uh 21:06neurotoxic compounds from the brain So now we know that it helps to remove amala beta in Alzheimer's diseases and 21:13Parkinson's disease And uh just yesterday there was a really exciting paper that came out with early clinical 21:19studies from from patients with Alzheimer's disease where they did a surgical repair of this lymphatic 21:25vasculature and and the early reports are an amazing um kind of benefit to 21:30these individuals that had Alzheimer's disease and it's kind of gone viral and and interestingly one of the the major 21:37voices that they they keyed in on for the perspective was the the postoc that discovered it at UVA So it's it's been 21:44cool to see that unfold recently Well John that's that's amazing You know in my field as a pure mathematician a 21:51result that was proven 20 years ago is considered recent But what you're describing obviously is quite 21:58groundbreaking It represents a paradigm shift and it allows I guess many more 22:04different kinds of scientists with different types of expertise to be significant participants Sounds like 22:09Nobel Prize winning work Yeah I would put my money on that I think he's very deserving He was he was doing 22:15neuroimanology before it was cool It actually UVA was one of the first places to have a a dedicated neuroimanology 22:21center Um and it's uh lucky to have been involved in the early stages of the 22:28field and uh you know really grateful that that UVA invested in in neuroimology at that time Do you still 22:35communicate with Yoni he's gone on he's become world famous and I believe is at WashU in St Louis Are your team still 22:42collaborating yeah I Yoni is like family I was out to see him a couple weeks ago He's he's a very good mentor Once he 22:49invests in you he invests in you for life So you know my my kids when we drive out to Corros and we go by his old 22:55house they say "Oh there's Uncle Yon's house." And Oh wow It's been cool because he's developed this pipeline of 23:00new scientists and seeing them and some of them are trying to come back to UVA to start their own lab So it's it's it's 23:06a really nice community since neurominology is so new in in the field of science there was a really 23:12opportunity to to establish this dynamic and open environment that that 23:18encourages trainees to to be really involved and I love going to those meetings and and seeing people like 23:24Yonyi and and Beth Stevens from Harvard and the the whole community is just is 23:29is a lot of fun and it's it's what science should be So now turning to the 23:34the projects that really drive you that that that you wake up every morning wondering about the problems in the 23:41brain Can you describe some of the specific research that the Harrison 23:46Center is going to be undertaking yeah so we're actively involved in trying to 23:52harness the immune system to help eliminate ner degenerative diseases We're studying right now is Alzheimer's 23:58disease And it's interesting uh that rewind back 15 20 years ago it was that 24:04disease everybody was just looking at neurons that was that was the focus but with uh advancements in genetic studies 24:10we know that many of the genetic risk factors for Alzheimer's disease are only expressed by the immune cells of the 24:17brain the microg ga um these have the the name of mini glue the forever we 24:23just I guess scientists just thought they were the glue that was holding the neurons together in the brain But now we 24:28know they they're the guardians that that help to eliminate these neurotoxic 24:33compounds in almost every neurogenerative disease that you can think of And and for whatever reason 24:39over time they become dysfunctional and once they go off the rails um they just 24:44keep on perpetuating inflammation um and cell death That really is the thing that's the culprit that's really pushing 24:50it further and further down So uh we're kind of using the same ideas that we had 24:58back 20 years ago to harness the immune system to fight cancer We're we're trying to harness the immune system to 25:04recuperate those beneficial responses of the immune system And back to a point that we had earlier you know most 25:10biological systems are more plastic than we would think Talking about the plasticity of the brain many immune 25:16cells have incredible plasticity too So there is a real opportunity to reprogram them for good So in analogy or maybe 25:25directly related to your earlier work on multiple sclerosis where you had the exhausted tea cells you you had success 25:31in re-energizing or reactivating those tea cells Is the idea to replicate some 25:37of that success here yeah for sure I mean in terms of reactivating tea cells the one thing with glyopblasto is that 25:45for whatever reason tea cells don't function very well in in brain tumors they do a lot better in tumors outside 25:51of the brain And there's many reasons that are thought to contribute to that So that is a major crux of what people 25:58are going after how to rejuvenate tea cells to remove tumors The other thing is the immune system's amazing In 26:05addition to eliminating cells it also plays this very important role in terms of being a protector eliminating and 26:12basically engulfing and clearing away damage And this is a vasculature So 26:17there's both at the at the systems level with vascular and lymphatics but you can also think about it too on the cellular 26:23side of things There's specialized cells that are like pretty much garbage men that go around the brain and kind of 26:28chew up garbage that could cause problems to the brain Many of the same themes that that people are hearing 26:34about in terms of the cancer space that we're you know a couple decades ahead of where we are in the neuronology space are themes that are coming Uh so one of 26:41the things that you know listeners may have heard of are CT cells and these are like engineered tea cells that are like 26:47awesome fighters to remove tumors People are working on CAR microg GA So they're 26:53genetically engineered microg GA that have these beneficial roles that that our micro GA used to have earlier in 26:59life um that help protect the brain and um there's a lot of uh emphasis both 27:04academic and also in an industry to develop these car micro GA to to target 27:10Alzheimer's disease and other neurogenerative diseases So if in your family there's history of Alzheimer's 27:17which is very common Yeah There's genetic environmental there's it's it's really multiaceted and you know it's I 27:23think it's like one in six or one in seven over the age of 65 Here's a question With the therapies that you're 27:29you're hoping to to develop these synthetic micro GA cells for example 27:34would the idea then be to somehow prophylactically prescribe these as 27:40therapies to someone who has a history or or a high likelihood of developing Alzheimer's because as I understand these diseases could take 10 to 20 years 27:46to develop Yeah So that's that's definitely one of the strategies that we spend a lot of time thinking about and 27:52and we're working closely with Rich Price in the biomedical engineering department here at UVA Um he has 27:59expertise in focus ultrasound and also genetic modification And we are co-mentoring a really talented graduate 28:06student that is is is basically trying to do just that but with uh genetic uh 28:12manipulation So it's not actually a cell but actually trying to genetically modify the microgle that are already in 28:18the brain and using focus ultrasound to target the specific regions and get it across that bloodb brain barrier So uh 28:25another thing that we think about like prophylactically getting back to this brain drainage uh discovery that was 28:31made at UVA is um so we we're studying it a lot in the context of traumatic 28:37brain injury So in uh you know obviously with traumatic brain injury you have a 28:42much higher likelihood of developing talopathies like CTE which is what's become popularized because of NFL What 28:50remains unknown is you know why certain individuals uh are more prone to develop those issues later in life And what what 28:58our work has shown is that if you have a pre-existing impairment in this pathway and then you receive some head trauma it 29:03it makes things a lot worse And on the other side of that that if you rescue that after a TBI it can limit uh this 29:11ner degeneries later in life So the thought would be you know right now we're kind of saying like oh it's fine 29:16to go back to practice or it's fine to go back to your military involvement um 29:21because you seem cognitively intact But a more empirical way to maybe address 29:27whether that individual is is functionally safe to reenter those types 29:32of situations would be to functionally understand if their lymphatics have returned to normal Is this something 29:38that can be tested so there have been some major advancements in terms of 29:43being able to to image uh lymphatic functionality and structure in humans 29:48and and that's a very active area and and there's a lot of hope there and and there there was a a Parkinson's disease 29:55study in in nature neuroscience a couple years ago really making that connection uh correlating uh a cohort of 30:02individuals that had a lymphatic impairment to develop in Parkinson's disease uh later in life So that is a 30:09hope and and it's it's interesting various people have shown it in various neurological diseases but in in our 30:14disease you know there's this growth factor that you could either put on the skull or inject into the brain fluid the 30:21CSF that kind of you know is is is washing the brain and it can boost the lymphatics uh pretty quickly and has a 30:27pretty profound effect in our experimental models So there there is hope that there could be a return and I 30:34think looking at lymphatic function could really give you a sense like of your neuronal health and your aging 30:40status and you know I was thinking like we go in for certain tests at certain periods of time like why not look at 30:46your lymphatics too Yeah that's exactly what I was thinking Every time I go for my annual checkup they take two vials of blood I'm not sure I'd like the idea of 30:52them taking you know a cc of my cerebral spinal fluid but but maybe we need that 30:58Yeah there is a little bit of an aversion to taking CSF but it provides an amazing window into the brain um at 31:05the molecular and cellular level There are facets you can get from surveying 31:11the CSF fluid that you can't get from imaging That being said you know some of the imaging is getting really good at at 31:18detecting the functionality and also the the structural features of the lymphatics So there there are multiple 31:25ways that we could uh start screening uh these patients probably in a in a in a way to take some of these uh treatments 31:32that that uh can have a real effect and and put them in play to really make a huge difference in their life So I'm 31:39sitting here wondering the experiments that you perform I assume you're performing them on mice What are the 31:45test vectors right There's various animal models that that that we're using Um we also are looking at at patientder 31:53derived cells Um so we can uh basically reprogram stem cells to be micro glea 31:59and they in a petri dish literally growing Yeah Yeah Yeah Okay Yeah So one of the one of the uh genetic risk 32:06factors that we're studying is is a gene called imp And there's individuals that have this mutation um and it's a gain of 32:13function And you can actually take their cells and and study how their micro glea are dysfunctioning And then you know I 32:19was actually on a call earlier where they they were doing just these studies where you know seeing that dysfunctional 32:27microgle from that patient you know basically drug screens or or or compound screens to to see um what it likes and 32:34what it doesn't like so you could you know target it better There's various ways um but you know a real power is you 32:42know we removing certain proteins that we think are important and uh either eliminating them or adding them in 32:49higher amounts and saying does modifying this one variable in a disease context does it have an effect and and also 32:56looking at it both before disease and after the onset of disease to really say 33:01like do we have to hit it prophylactically before there's symptoms or can we also is there also a window 33:07where we could target it as the disease has already been diagnosed That's we always approach it like that just um to 33:13really get a good sense of how good of a translational target it would be So John thank you very much for that very 33:19colorful and instructive kind of show and tell about what goes on in the lab Here at UVA we are also a school So I 33:27kind of want to circle back to the story about your training You were mentored by Yoni Kipnis Of course here at UVA we 33:34want to largely be measured by the success of our students So now that you are running a center you are the big 33:42name endowed professor Give us the behind thescenes look at the science and 33:47what it's like for you to mentor students in your lab Yeah So uh you know 33:53going back to the the Stat Madness report uh that you highlighted earlier from a year ago that that was a study 34:01that was led uh 100% by a graduate student uh in the neuroscience graduate 34:07program Hannah Enterfeld and she was just fearless in terms of pursuing that 34:13it it um the project actually started at then the COVID so we you know we were um 34:18had restrictions in the lab and really had to communicate and collaborate with 34:24people in a different way So uh we took up some collaborations with another group at Wisconsin Tyler Uland And uh 34:32she it was it was incredible to see uh and I always I was actually telling a student about that yesterday From the 34:39initial working on that project to the submission of that paper to sell it was a year Um and it just shows you when you 34:46catch on to something good and you put your your heart and soul into it and you almost become obsessed with with wanting 34:53to understand to move it forward uh how how quickly uh science can move And it 34:58was it was an amazing um ride And she was working closely with a really talented uh undergrad named Koko 35:05Hollywood who interestingly uh is is putting together a neuromimanology uh 35:11symposium a Gordon research conference uh with a professor from Harvard and she's now in his lab Um and so actually 35:18we were talking about her earlier this week Uh but Hannah Hannah moved on She's now a postocck at Stamford um doing 35:26incredible uh work there I'm actually going out there in a couple months Um 35:32she and another posttock are are um hosting me for a talk But we're hoping 35:37to get people like her back cuz they're they're amazing and um they're they're the type of people that that make UVA 35:43better And um yeah they're going to do much more incredible things than I ever did in in my career Uh just cuz they're 35:50they're just a real joy to to see succeed and the students you have in the lab now the future Hannah's Yeah Yeah 35:58You know try and really create an environment that's fun Um you know we have our uh third annual spirit week 36:05coming up There's a lot of laughs No question is a bad question I think one 36:10of the things that we've really benefited from is is having a lot of interaction with the the undergrads Um 36:16so every summer we have a whole core of undergrads and they're always at meetings I encourage them to to ask 36:23questions even when they're not prepared And many of them come back and say "Thank you for for encouraging that because it's definitely helped me in my 36:31PhD work now wherever they are or in medical school in terms of voicing their ideas because that helps to to move 36:38things forward I'm co-mentoring a couple students one with Bill Petri um on neuroid and then we have this 36:44translational work that Josh Samuels is working on with Rich Price And you get to a point where they become your 36:51colleagues and collaborators And it's like you know you know that you're they're ready to move on when when 36:57you're talking to them just like you're talking to somebody like Yoni Kipnes or Bill Petri Oh yeah I totally know what 37:02you mean Where you get to share and in some cases maybe even relive the excitement that we had when we were 37:09graduate students But to see that repeat itself over and over again Yeah In addition to the science that's probably 37:15one of the most exciting things that a professor can you know look forward to Yeah So you mentioned something you said 37:23uh we have an upcoming spirit week So I know what spirit week meant to me in high school and college I don't want to 37:29repeat that but what does spirit week mean uh in the Lucans lab yeah So I mean it's the themes vary It's it's it's it's 37:37a democracy We actually had a vote today The students they have a good time with it you know everything from like pajama 37:43day like is back in high school They had it dressed up like John day John that is awesome So along those lines the 37:50students that work with you they must be super pleased privileged to have you as a mentor And so for students that might 37:57be listening uh how can they get involved yeah So the the easiest thing is just to email me or uh you know 38:05there's tons of information on our website what individual people are working on in terms of projects You can 38:11you can interact with them email them Um you know if if people are interested to 38:17take a lab tour or last week we had a first year join us for lab meeting to see what it was all about This is 38:23something we do all the time Um you know we also are involved in this mini medical school program that happens at 38:30the hospital where anybody from the community can come into the lab for a couple hours And there are people that 38:35change courses and get inspired Uh there's actually a graduate student in our program that you know has come back 38:42to it as a second career because of a personal experience and it's it's really um inspiring to see that and it doesn't 38:49matter if you have experience I think the passion and um the the want to to to 38:56get better and and to uh you make a difference is is all you really need and and in terms of science um you know I 39:03mean if an immunologist can do neuroscience like there's no stopping anybody I mean it's uh that's the great 39:10thing about uh research if you know you can put in the time and effort and you'll get uh results and move the field 39:17forward Well if you're listening there you heard it If you're invited to attend 39:22visit John Lukan's lab day Uh send him an email And I think you can tell from this conversation he is a very welcoming 39:29and uh easygoing scientist Time is running short I'd like to ask all of our 39:35guests questions that have to do with their origin story I know we kind of talked about that going back to Yoni 39:42Kipnness but I want to actually rewind the clock a little bit further So when 39:47did you know you wanted to become a scientist say an immunologist so I knew I wanted to be an immunologist Uh my 39:54senior year of college when I took immunology I I actually got a B in it Um I didn't do that that that good um in 40:00the class Um but I loved it because you know immunology is is was fascinating to 40:06me because I I got into science because I wanted to make a difference to help people that were suffering from an 40:13illness Um so you knew you wanted to go into medicine or biomedical research yeah I I I didn't think I had the the 40:18the chops or the wherewithal to deal with blood or surgery Um but I I knew I 40:24liked you know working with my hands to like solve problems and and that and 40:29that's what research is You know you you have an idea and you try to use tools to to answer it or disprove it And um you 40:36know the thing that took me to immunology is it's hard to find a human disease where the immune system isn't the major player You know you can think 40:42of autoimmune diseases like lupus or you can think of cancer where the immune system can be harnessed to kill cancer 40:49cells Obviously infectious disease and and now we know that the the immune 40:54system is a big player in terms of regulating most neurological diseases too Everything from neurodedevelopmental 40:59disorders to to diseases later in life like ner degenerative diseases And and that that was really what drew me to to 41:06immunology as as a passion and research And and that's that's kind of how it started John I think we can talk forever 41:13here so we do have to cut this short Um this is a fun moment a joke fun story 41:19from childhood Tell us something that we could end this conversation with that tells a little bit about John Lukans as 41:27a person but not a scientist Maybe I'll tell you what I'm going to do after this I'm going to go for a run and there was 41:33a new Kendrick Lamar album that dropped a couple hours ago I'm going to listen to that Then I'm going to go home Um I 41:39think there's a UVA game at six o'clock St John's And then um I'll hang out with my kids We're playing indoor soccer in 41:46the house now So we'll do that And then and then that's that's a glimpse of the 41:51the rest of my day Maybe that helps Well hey you guys have been listening to 41:57who's in STEM We had to finish that way if you're going to follow UVA basketball 42:02So John UVA is lucky to have you This has been a super conversation Good luck 42:08with the Harrison Institute the center that you'll be guiding Good luck with your hiring And I certainly am delighted 42:16to share that you are fulfilling President Ryan's mission for all of us 42:21here at UVA to be great and good in everything that we do So I'm Ken Ono 42:26STEM adviser to the Provost and the Marvin Rosenblum Professor of Mathematics and you've been listening to 42:31Who's in STEM Who's in STEM is a production of WTJU 91.1 FM and the 42:37office of the provost at the University of Virginia Who's in STEM is produced by Katherine Cosum Cla Keren Benjamin 42:43Larson Mary Garner McGee Katie Nichols and Ria Verma Our music is composed and 42:48performed by Robert Schneider and John Ferguson of Apples and Stereo Follow us on Facebook Instagram and Twitter Listen 42:55and subscribe to Who's in STEM on Apple Podcast Spotify or wherever you get your podcasts We'll be back soon with another 43:02conversation about scientific and technological innovation at the university