Brain Research with the Abisambra Lab

Brain Research with the Abisambra Lab - Podcast Transcript

Alicia: Welcome to the research podcast. I’m Alicia Gregory, Director of Research Communications at the University of Kentucky. June is Alzheimer’s and Brain Awareness Month, and today we’ll highlight the Abisambra Lab at the UK Sanders-Brown Center on Aging. In 1985, the center was one of the original ten Alzheimer’s Disease Centers funded by the National Institute on Aging. In this podcast, we’ll meet Joe Abisambra, and three of this lab trainees; Sarah Fontaine, Shelby Meier, and Brittani Price.

Joe Abisambra: My name is Jose Francisco Abisambra. I’m an assistant professor at the Sanders-Brown Center on Aging at the University of Kentucky. This is my lab – the Abisambra lab – and we focus on tauopathies. The most common of which is Alzheimer’s disease.

I was born in Miami, Florida and I lived there until I was six, and then I moved back to where my family is from in Columbia. I lived in three different cities on the Atlantic Coast and Pacific Coast, and then in Bogota. And so Columbia, at the time especially, was going through a civil war. A lot of the resources were really being channeled towards fighting this war, and I came to the United States – took advantage of my dual citizenship. I established myself in Florida, went to Saint Leo University where I finished my biology degree, got a master’s degree at the University of South Florida, and then my PhD also at the University of South Florida.

Joe Abisambra: What really clicked was when I was in my second year of medical school, and I started doing some histology and I found neurons. And… in the cheesiest way, neurons are the most beautiful cells in the universe. They are elongated, they have these processes that are very unique, they’re high maintenance, but their functions are critical for everything that we do and clearly I hold them in very high regard. After that, I just wanted to know more about them. So I was going through my master’s degree. It was about three o’clock in the morning and I was looking at these immunofluorescent slides – lost complete track of time – and I had one of those eureka moments when I found something that nobody had ever seen before. And they say that those moments come up maybe once or twice in your career and it’s really hard to describe how filling, how exciting, that is.

When I was getting my PhD, I had a rare opportunity to be involved with some of the memory screens with patients. One of the advantages of being a dual citizen and being exposed to both cultures, I’m fluent in Spanish. It’s actually my first language. And I got to see firsthand what an Alzheimer’s patient…. looks like, how this Alzheimer’s patient behaves, and how devastating it is for the family. So I went from the basic science on the bench to the impact it could have on society.

Joe Abisambra: One of the things that I love the most is to be able to mentor. So I have a very young lab and ultimately I recruit them based on one thing, which is the same thing that I grew up with, is curiosity. There’s a lot of talent at UK. The students here are fantastic and they come to me at this point, which is- which is… I can’t ask for anything better, and the potential is huge. So from my perspective, being able to help take that potential further is immensely satisfying.

My favorite time in the lab is to meet one-on-one or in the lab meetings with people in the lab, and to have them present to me the data. The most exciting thing at this stage, now that I’ve been here for three years, is to see these students formulate their own questions and find their own methods to answer these questions.

Sarah Fontaine: My name is Sarah Fontaine and I’m a senior scientist in the Abisambra lab.

For probably most of my childhood up until I was an undergrad, I wanted to be a veterinarian. So I was volunteering with vets, on the vet track, and then I started doing research in labs because I got bored in undergrad – which I’m not sure people really admit to, but I was pretty bored – and once I started doing research it was all over for me.

Sarah Fontaine: I think I decided I wanted to actually do research instead of veterinary school or medical school my senior year of undergrad. So in the fall, I was sitting there talking to one of my mentors and I was like, “Doctor Hoosier, what do I do about school and med school and grad school?” And he looked at me and he goes, “Grad school.” And he’s like, “You like knowing the answers to questions and this is the best way for you to do so.”

So I went to Purdue University for undergrad, and then I went to the University of Bath in Bath, England for my PhD. After that, I did my first postdoc at Indiana University and then my second postdoc was at the University of South Florida.

Sarah Fontaine: I really think solving problems and answering questions. So really sitting there thinking about, “How does this work?” and being able to come up with ways to test like, “I think this is how this works” and actually seeing results of this is what you thought, or this is completely different from what you thought, but even in a more interesting way. So it’s really kind of the problem solving and the puzzle solving that I really enjoy.

There have been times when I’ve been sitting there banging my head against the bench – metaphorically speaking, cause I wouldn’t do that in real life – going, “Why aren’t you working?! Why aren’t you working?!” But when it works and you get an answer, it’s the most satisfying thing in the world.

Sarah Fontaine:) Everybody is really great actually. This is one of the best teams of people that I’ve worked with at a lab. Everybody is very committed, very motivated, and technically very able. So we are able to get a lot of really good work done and I know that everybody is as careful a scientist as I am, which is very reassuring.

Shelby Meier: I’m Shelby Meier and I’m in Joe Abisambra’s lab and I’m a graduate research assistant.

I grew up in a really small town in northern Kentucky. It’s called Independence, Kentucky. There’s maybe only like 10,000 people there, and then I moved here to Lexington to go to college.

Shelby Meier: I had a lot of different things that I wanted to be as a kid. I wanted to be a pediatrician at one point, a journalist, an actress, and then once I got a little older, I kind of finally settled in on medicine and wanting to be an orthopedic surgeon.

I actually joined at Joe’s lab to boost my resume for med school. I started doing undergraduate research my sophomore year and I came in here and I got a lot of experience, and for all of my undergraduate time I had still planned on going to med school. And then about three days before the graduate school deadlines for applications, I decided I wanted to go to grad school and stick with science. I just couldn’t give up doing my research in here.

Shelby Meier:  I did my undergrad here at UK and I’m continuing my post-grad work here at UK in the Integrated Biomedical Sciences Program. And so, I’ll be getting my PhD and I’ll be joining Joe’s lab, and so my PhD will be in physiology. And my PhD work, is hopefully going to focus on protein synthesis and progressive and injury induced tauopathies.

As cheesy as this sounds, a lot of my inspiration has come from Joe. This was my very first research lab that I’ve been in and Joe has afforded me every opportunity to experience the best parts of science. I’ve gone to conferences, I’ve won poster awards, I’ve gotten to present at different places, I’ll be getting to go to international conferences this coming year, and besides all of that, Joe’s scientific integrity and his creativity in the work he does, it motivates me a lot to have the highest standard in all of my work as well.

Shelby Meier: This team is fantastic. I’ve been here a very long time. I’ve been in Joe’s lab since the very beginning and a lot of people have come in. It’s kind of a transitional lab. Everybody has very high expectations and everybody succeeds, so it’s really great to see those kinds of people come in, and Joe brings in people of the highest caliber. So I get to learn from people that are very experienced, very intelligent, and I have very good examples for where I want to be in the next few years.

Brittani Price: My name is Brittani Price. I’m a first-year graduate student in the lab.

So I’m actually a product of Appalachia and I grew up in Greenup County, Kentucky, which is about two and a half hours east of here in a very rural area. It’s all farmland and…. nothing really there.

Brittani Price: The whole time that I was growing up I always thought that I wanted to be a doctor, and I think that happens to a lot of people that end up going into science. When you come from a very small town and you like science and you like math and you’re good at those things, everyone’s first instinct is, “Well, you’re going to be a doctor. You’re going to be a physician and you’re going to come back to the area and you’re going to treat everybody who’s sick.” And I think for a long time I was okay with that idea and I just sort of adopted that idea as my own, and it was my junior year of college that I really started to think about, “Do I actually want to be a doctor?” And that’s kind of when it hit me, “Maybe I don’t.”

And I think everyone has a very pivotal moment in their life especially when they’re about to kind of do the thing that’s going to make or break their career – like take the MCAT or not take the MCAT – where you really, really think about it. And for me, there are certain members of my family that are affected by a disease that has no current treatment, and I kind of pictured myself as a physician looking at a patient that suffers from the same disease they do and I just thought to myself, “I can never be a doctor because I could never walk into a room and look at a patient and say, ‘I’m really sorry. You have this and there’s nothing I can do about it.’” And that’s when I decided that medicine wasn’t for me, but I was very fortunate in the sense that I got to research in undergrad so I was exposed to a career that would allow me to affect medicine in a positive way, and hopefully affect patients that suffer in that way in a positive way.

Brittani Price: So I went to Morehead State University, which is in Morehead, Kentucky. There I was able to do undergraduate research with Dr. Kurt Gibbs and I worked on spinal cord injury in a Xenopus laevis model.

I will have to give my undergraduate research mentor all the credit in the world as far as inspiring me to become a scientist. I really battled with that decision between medical school and graduate school for a really long time, and I ended up speaking to him about it and he was the one person that was able to convince me that I was actually smart enough to do science. Because when you come from an area where I came from, there’s a connotation that comes with being from Appalachia. And it’s this idea that because you grew up essentially in the cow pastures, you’re allowed to be dumber and people expect you to be dumber. And that’s not always the case, but that is kind of a hard stigma to bypass. And so, for someone to actually sit you down and tell you, “No, you have a lot of potential in this area. You can do this.” That makes all the difference in the world.                    

Brittani Price: This lab is by far the best lab that I’ve ever worked in as far as a team atmosphere. Everyone helps everyone. Everyone’s willing to let you bounce your ideas off of theirs and it’s a really innovative environment. And you don’t find that everywhere, and I’ve been very, very, very fortunate to work with this team of people. And I look forward to coming to work every day.

Joe Abisambra: So our lab is in the Sanders-Brown Center on Aging. This Center has been a pivotal aspect of the University, partly because we have an Alzheimer’s Disease Center designation. There are about thirty other institutions in the country that have this designation and we are one of the few that have had the designation from the beginning of the program in 1985 through today. And just last week we got our ADC renewed – we have to compete for this every five years. So this funding helps support cores at our Center including the brain bank. When I was at another institution, it would take me six months to get human tissue that I requested from other brain banks. Here I can contact our neuropathologist and get a very thorough clinical evaluation of the tissues, get the tissues themselves in a very timely manner, and I can go back and discuss with the clinicians and the neuropathologist what was going on with this patient because they’re all here. There’s no other place that I can think of that has that community based resource.       

We have one of the best brain banks in the world here at the University of Kentucky

Joe Abisambra: Our main focus is Tau. Tau is best known as a microtubule stabilizing protein, which is very important for neurons because it essentially forms the pillars on to which cargo is transported along this beautiful svelte cell. And for some reason, Tau falls off the microtubule and becomes pathological. It chokes the neuron. And this happens not only in Alzheimer’s, but in other twenty known diseases. So our goal is to understand these processes. How does Tau become abnormal? How does it become pathological? And in doing that, we hope to identify novel therapeutic targets.

In studying tauopathies, including Alzheimer’s disease, we hope to impact a population of more than nine million people in the United States and more than 30 million people in the world.

Joe Abisambra: Speaking of Alzheimer’s alone, by 2050 if we don’t do anything to stop this disease, we’re going to end up spending 1.2 trillion dollars, which is one third of the federal budget. Not to stop a disease, but to treat a condition. To maintain a constantly deteriorating quality of life. There is no cure for Alzheimer’s or any of these diseases, so we hope that by identifying novel therapeutic targets and being able to intervene to stop the process, we might be able to improve the quality of life of these people, have a social impact, have a health impact, and an impact on the economy.

Shelby Meier: The big focus in our lab is neurodegeneration and the endoplasmic reticulum, and we’re looking at inhibition of a specific kinase. And so I have been very involved in that project, treating the animals and studying how inhibition of this kinase affects pathology of the disease and neurodegeneration in general.

From some preliminary data, we’ve seen a little bit of tissue sparing, a little bit of activation of an immune response. So that would be absolutely incredible to have some sort of drug that we could give people after they received a traumatic brain injury, that would reduce some of the long-term side effects like mood swings or memory loss. And a lot of traumatic brain injuries are linked to an increase for your chance of Alzheimer’s disease or other neurodegenerative diseases. So being able to come up with even a path that’s being activated in that disease, or a treatment for this outcome that would be really, really cool.

Sarah Fontaine: UK is phenomenal. It has all of the resources that you could possibly imagine from the Alzheimer’s Disease Center with the brain bank for patient samples, we can actually correlate what we’re seeing in a tube to what happened in a person. To the number of different cores. We’ve got access to top facilities. We can make protein. We can do mass spectroscopy. We can do cryo-EM, which is a fantastic technique for looking at the details of the synapse. The cores, the facility, and the people that we have here, are just world class. So it’s a great place to be doing research.

Joe Abisambra: UK has a very particular characteristic that is… far exceeds most of the other places I’ve been to, and it’s that sense of collaboration. It’s a sense of community. And I think that permeates from Lexington itself. That this is a community that cares about everybody involved in that community. This is the place where I’ve been able to find – very easily – collaborations with some of the best scientists in the world. And so, the opportunities here, the talent here, and that nature of collaboration, of wanting to help each other, is unique.

Shelby Meier: UK is one of the best research environments that I’ve ever seen. The collaboration here is incredible. Not only that, but your upper level people, your P.I.’s, your senior research investigators, they are so helpful and so welcoming. They’re very well trained, but they can bring me in and they can say, “Okay. Here’s the basics, here’s what you need to understand, and this is what we’re going to teach you.” So it’s a really great environment to learn and feel comfortable making mistakes that you can learn what you really need to know.

Brittani Price: I think for anyone who’s thinking about doing science, if you have this burning question or if you… you know if there’s a disease that you have a personal experience with and medicine hasn’t figured it out yet and you think that you want to spend your days figuring that out, pursue it a 110% because you won’t regret it. And for anyone who comes from a disadvantaged area that might think that they’re not smart enough or that other people might not think that they’re smart enough, that doesn’t matter. Half of this is work ethic, half of this is really just trying to figure something out. And if you’re willing to put the time in, you are smart enough. If you really want to do it, don’t let anything stop you.

Alicia: Thanks for listening to the research podcast. To subscribe to our podcast on Soundcloud or iTunes, search University of Kentucky research media, and visit our site; reveal.uky.edu