Kaitlin, welcome to our OneNeuro Student Profile Series. To begin, please talk about your academic journey thus far.
Currently, I’m pursuing an MD/PhD, and I’m finishing my seventh year of what will be a nine-year program. That’s an individual trajectory for everyone.
The most common trajectory here at Johns Hopkins is you complete the first two years of medical school and then you work on your PhD. My PhD is in biomedical engineering, and I finished it in May 2024. Now I’m back in medical school, focusing on my clinical training.
Talk about your thesis – what is your focus?
My thesis is focused on helping to develop and identify biomarkers for Alzheimer’s disease. Biomarkers are measures that we can take in individuals while they’re still alive and that are readily accessible. For instance, I’ve been focusing on imaging-based biomarkers through MRI; the idea being that we can use them to glean, hopefully, what is happening deep down at the molecular scale in order to make a diagnosis and ultimately manage Alzheimer’s disease much earlier on. Towards this work, it has involved building methods that allow us to integrate the information available to us across scales. We do this in the hopes of linking what we see through MRI at the tissue scale to what we’re seeing more at the cellular or molecular scales. Traditionally, we’ve observed these scales postmortem on autopsy, but we’re also beginning to see biology at even a more granular scale, with spatial transcriptomics. I’ve worked to develop two different methodologies that allow us to model data at the different scales and then align it into the same coordinate system so that we can begin to draw these correlations of what the biology is doing at the different scales that we may observe.
What is the concept of mini-brains?
Mini brains relate in part to the notion of biology at different scales. We have a lot of robust data sets that cover the entirety of the mouse brain. We look at gene expression and cell types now that come to us as spatial transcriptomics or we can look at more traditional clinical images that cover the entire mouse brain at a tissue scale (e.g., MRI).
In part of the representation I’ve built, it allows one to model data at whatever scale we get it at. Yet importantly, we are often unable to manipulate and compute with data at these scales in real time. What I’ve done is build what you can think of as an approximation scheme. You can select the resolution or the scale you want to represent an underlying data set at that might be different than the scale you capture it at. You can determine what strength prescription of glasses you want to use in terms of how blurry of a picture you desire, which will save on the amount of time and memory that is needed to really store that. I’ve made indications of a mouse brain specifically taken from a three-dimensional image, for instance, but at different resolutions using this approximation scheme that can be used in different applications depending on the need.
Image: 3D Reconstructed Distribution of Tau Tangle Pathology in Advanced Alzheimer’s Disease – Tau tangles (black dots) detected by machine learning algorithm in high resolution digital pathology images taken post-mortem of brain tissue in the medial temporal lobe (MTL) and mapped to 3D space of MRI where global distributions of tau tangle pathology are computed across 2D tissue sections within whole 3D structures of MTL including amygdala, entorhinal cortex (ERC), and regions of the hippocampus, which are affected in early Alzheimer’s Disease. / Kaitlin Stouffer
Are you still working on that project?
In biomedical engineering, one of the main things to keep in mind is that you might be developing methods with a particular problem in mind, but the goal is, obviously, to see those methods then spread out/expanded and used to do different things. So this sort of approximation and data rendering at different scales is meant to feed forward into how we might be particularly modeling the spatial transcriptomics data sets that are very high resolution. We have worked with colleagues at the Allen Institute for Brain Science in Seattle on their data, and, I would say, moving into the future where I really hope to be using this at the scale of a human so that we can begin to represent and tie together what is happening in the human brain that we can see again through MRI, with what is happening at the molecular and sub-micron scales.
Have you always wanted to be an engineer or a scientist or medical doctor?
In all honesty, I wanted to be a Rockette at Radio City Music Hall. That was what I wanted to be during my first 10 to 12 years of life.
I would say, though, that for quite a long time, I’ve been captivated by the questions of science, and yet I have always really enjoyed the methods and the modeling of mathematics. I majored in computer science as an undergrad, and I chose that path because it had some of this flavor of trying to build tools and methods that were maybe more rooted in modeling and mathematical patterns to be able to understand and attack the problems that we confront in science. Medicine came into play as I was trying to translate biology into, fundamentally, the medical sphere. In terms of making a difference and accomplishing not just understanding but also impact, I was drawn to the medical sphere. I have a very soft spot for the patient interactions that you can achieve being in that clinical sphere.
One of my side hobbies is thinking about patient communications. I pursued a master’s degree in narrative medicine before coming to Hopkins. So, I’m thinking about how to formulate disease similar to what I’m doing, maybe not the science, but describing the disease in some sense as best fits the patient where something is going to be tailored differently to young patients, depending on what resonates with them, and how they want to cope with their disease. That aspect of medicine, coupled with this side of more technicality in building the tools that will help us understand what’s happening in the scientific domain are ultimately what I hope to be weaving together in a non-direct, very multifaceted path but ultimately to treat the whole patient – person and disease.
Narrative medicine, can you expand upon that, provide more background? Is that storytelling through medicine?
It’s becoming a much bigger thing. I met Meg Chisolm, who is a psychiatrist here at Hopkins and who offers a gallery course that I’ve helped to facilitate over the time it’s been offered.
I met her at the same time I started my PhD, and I told her that I have a background in narrative medicine, a degree that I completed at Columbia, one of the few places that offer formal study in it. And she said that she is focused mostly on arts in medicine, but really wanted to turn it into a more diverse humanities-based course in medicine. So right now, we’re teaching such a course to undergraduates, and it has been an elective for medical students, primarily fourth year students as they are transitioning into residency. During Covid we ran it online eight times – it’s a one-week course, and we included a few virtual galleries.
The course has complemented my journey through the PhD. A huge thing about it is being able to deal with ambiguity and embrace that, which is particularly important in the context of medicine where a lot of the technical training is rigid and algorithmic since, in a crisis mode, you want to know what to do and be able to get to the point when you have so little time with a patient. It is a constant balance. So at the end of each course session, we do a reflective writing exercise. I developed prompts that try to test and encourage students in being ambiguous. They definitely tend to have word choices that are maybe not so clear cut, for instance, describe the weight of the day: that could be the wait time, the waiting period, or it could be the heaviness of the day.
And people can take it in the different ways they want. We write to the prompts, and then we listen to each other afterwards and bring up similarities and differences in our experiences which continues to further the reflection experience. So to your question of narrative in medicine – I think of it as how do you use the template of a story in medicine, and that can be through a number of different avenues. It could be driving a doctor’s communication with their patient; it also could be for their patients to understand their journey through an illness. It could be for discussing ethical issues. I think all of them are interesting. I loved creative writing for a while, which is what got me interested in narrative medicine and the use of metaphor. And again, really trying to find ways to connect with the patient in a way that best serves them and likewise connect with the science since I do feel like it’s often so impenetrable to a lot of people, but there are a lot of things that can be understood, applied, and appreciated.
I also had the opportunity, through a Fulbright Scholarship, to spend the past year in Paris, France, and I worked with a longstanding colleague of Dr. Mike Miller, Dr. Alain Trouvé. He’s an applied mathematician. After working with him, I do feel like I’m sitting in this middle, which is really where I’m trying to be, to cultivate myself to be able to have feet in these different buckets, biology, mathematics, narrative medicine, humanities. For me, the PhD journey has been trying to understand the mathematics, to complement my medical and narrative medicine training.
It’s interesting to sit where I do. On the one hand I’m learning the mathematics, but then I’m the expert in biology, but then I talk to clinicians, for instance, and they’re the experts in the medicine, and I’m the one who is the expert on the technical side. Definitely kind of finessing and understanding how best to communicate ideas to pull all those different people in has been a huge part of my PhD experience.
Besides those that you’ve mentioned, are there others with whom you collaborate? Who else would you like to acknowledge as really core to your journey here?
Dr. Miller is, of course, amazing. He is my rock and a one-and-only human being. I’ve thoroughly enjoyed working with him.
On the clinical side, Dr. Marilyn Albert, who runs the BIOCARD Study, has really helped in situating what we do in the broader context of more the neurocognitive side. She also has generously shepherded us into being able to analyze the BIOCARD data and really take part in what is happening with that clinical trial. In pathology, we have started working with Dr. Juan Troncoso and recently Dr. Meaghan Morris, who is an MD/PhD graduate from here as well. She’s now a pathologist here, and we’re working closely with her. She is on my thesis committee, and she’s embracing the idea of the molecular scale tied to the cellular scale, and she has studied not just Alzheimer’s but other neurodegenerative diseases. Then there is Dr. Laurent Younes, also on my thesis committee, and he’s more in the applied math realm. Dr. Younes has helped in both straddling the implementation in terms of code and in the theoretical mathematics or statistics that will rigorously allow us to find correlations or in manipulating our data, representing it in a way that sits both with biology itself as well as longstanding mathematical tenets.
How will you remain immersed in your mathematics, your PhD, while at the same time being equally immersed in your medical degree?
I think it’s embracing the current stage that you’re in, with the notion that your end goal is to come to a more integrated position. That means having both feet in the medical school when you’re there, just like now, I haven’t done anything in the hospital other than the class that I’ve been teaching.
What drew me to Alzheimer’s in the first place was the clinical aspect of it, and I liked the theories of computational anatomy in terms of using math to describe the anatomical shapes of the brain and biological data. I also really liked the fact that I work with images or pathology specimens from humans. That was before I started with the mouse, but that drove me into this work. That speaks to the MD/PHD path – even if you’re working with mouse models or something else, what is driving you in the end is reaching back to the patients. So when I’m in the wards now for the next two years, what I hope to see is how I can use some of the tools that I’ve helped develop here in a way that seems manageable in a clinical setting. Because while we’d like to see them push through immediately, it’s going to be through understanding, through accessibility, through many nuts and bolts. Having that in mind – what are the problems that I see in the clinical sphere, and how might I address those? What potential problems, as well, in terms of the disease space am I seeing and might want to concentrate on in the future?
You mentioned that you’re starting back in pediatrics – have you worked with children before?
No, not yet – we do one rotation before our PhD. Five years ago I did OB-GYN, which I really liked. Typically we choose rotations we don’t think we’re going to pursue before working on our PhD, but seeing the babies was just great as well as connecting with the patients – it was a patient population I could relate to. I have not really worked with children, and I have very little experience working as a clinical figure in general, but here I have worked with many students. That also has been part of my PhD experience – learning how to manage and mentor students at the undergrad, postgraduate, and master’s levels. It’s going to be a whole different day in the setting of very sick children and also with their family members. I think keeping an open mind and really continuing to always turn, when in doubt, to my curiosity will be helpful.
Thinking about the students that you’re mentoring and if they want to follow your same path, or a variation of that path, what are a few of the skills or qualities they should have to succeed here at Johns Hopkins?
In this interview, we’ve underscored communication, which I think is key. Something else that I’ve done here at Hopkins is to give many presentations of my work. And while they take a lot of time to prepare, each time I do it, it helps me learn the material better and what resonates with people. I think recognizing communication as a two-way street, as they say in medical school, closed loop communication. You really want to be in all settings, not just with patients, but in all settings with communication, making sure that you can provide feedback to the people who are speaking to you, what you are hearing to really make that effective. I think that’s a skill across the board, particularly because everything is becoming much more integrated within subfields. It will become even more important because the innovation that exists out there is about bringing together different fields, approaches, and perspectives. I think that take us, as a society, to the next level of understanding and then of development.
Then another thing I struggle with, it’s always a balance of keeping an open mind, but then also moving forward and ahead in often a single competitive path. I do recognize that many times, when you’re in the application phase or another phase, you need to pull together a story that will explain why it makes sense that you’re doing this. And I have had many different pieces that I’ve tried to weave together. Yet something that I have really appreciated is being able to keep the pieces and weave them in a way that resonates with me. So I think keeping an open mind and being able to craft a unique path for themselves is something I would advise, both for sanity and for ultimate fulfillment.
In addition to your academic and clinical work, what else do you do to attain ultimate fulfillment?
I do love to travel. I have traveled and lived in a number of different places, South Africa, the United Kingdom, and now Paris. Immersing myself in new cultures is something that I absolutely love. I also enjoy walking and hiking, particularly, which I do with my dog. She’s a cavapoo that I got in 2020 during Covid, and her name is Brontë, after the British authors, Charlotte, Emily and Anne Brontë.
I’ve also loved taking the course I’ve taught with Meg Chisolm; I didn’t have the opportunity to take any kind of art courses in college. So while the crux of it is not to necessarily understand art, I have been exposed to so many different works of art here. We go to the Baltimore Museum of Art, the Walters Art Museum, and American Visionary Art Museum. It has been a pleasure to open my eyes to learning how to view art in a different way that really invites it in, and it has changed my experience when I go to other museums, such as when I was in Paris.
For the final question, what do you think OneNeuro could do to bring us together?
I like the idea of integrating art into some of the activities OneNeuro could offer.
I also like the idea of communication. What would really intrigue me is the two-way street of communication, can we bridge it to some humanities fields? From a brief interaction or dialogue, how can I take what they’re doing in X field and apply it to the context of neurology research versus how can they take what I’m doing in neurology research and apply it in their field. That’s obviously saying OneNeuro coupled with other fields outside of it. There are many people interested in the brain for different reasons. When you talk about brain art, it is not just the pictures that we can generate, it’s also that the brain is generating responsiveness that numerous people are studying in the context of many different things. There are opportunities for intersections there.
I think arranging opportunities to engage in these sorts of two-way discussions, which could take the form of speed dating or coffee chats. You could have five speed dates with people who are from different fields than you and then a conclusive wrap up discussing how those fields inform others. I think it’s setting up the opportunity for the webs to grow. I really like the idea also, particularly given seasonal weather, to arrange something outside and have people trickle in and view an exhibit from the perspective of, well, this is science, but it’s also art and talk about it.