Migraine Research, Advocacy, and a Little Bit of Grace and Compassion: A Conversation with Mandee Schaub

“What I’m working on is small molecule antagonists for PAR2, and I’m hoping that one of them becomes a drug that we can administer to patients. There’s already a PAR2 monoclonal antibody in a phase 2 clinical trial, and we’re super excited about that, because this may be the successor to the CGRP story – we have monoclonal antibodies for CGRP, and small molecule antagonists for CGRP, and hopefully we’ll have a similar anti-PAR2 duo that works really well for patients.” – Mandee Schaub

Mandee Schaub, MS, is a researcher and PhD candidate in the Department of Neuroscience at the University of Texas at Dallas, US, and the trainee representative on the MSC editorial board. Her work focuses on the role of the trigeminal ganglion in the transmission of pain signals contributing to the pain phase of migraine and headache disorders. Using preclinical models and human tissue from organ donors, she aims to understand the pathophysiology of headache and identify new therapeutic targets. In addition to her research, Mandee is a person living with chronic migraine and persistent daily headache. She is passionate about reducing suffering of all people living with headaches and hopes to make a positive impact throughout her career with research, advocacy, and public education about migraine and headache disorders.

In this Migraine Science Collaborative interview, she spoke with Neil Andrews, a science journalist and the executive editor of MSC, to discuss her research, her advocacy efforts, and much more. The interview has been edited for clarity and length.

How did you become interested in doing migraine research?

I am a chronic migraine patient – actually a 24/7 headache patient. When I was 12 years old, I had my first migraine attack. It was the first one I ever had with aura, and I thought I was going blind. My mom picked me up from school and took me to the eye doctor, who diagnosed me with migraine.

Very quickly after that, my headaches became chronic and then daily. By the time I was 13, I was having daily headaches, and we had no idea what was wrong or how to fix them. I lived in a rural area in North Carolina, and there was not good access to care. A headache specialist came down from Chapel Hill once every three months to check on people, and he’s who I saw, but it wasn’t a sustainable method of care.

At the time, they really didn’t have anything to offer children with severe migraine, and I thought that someone really needed to fix that. But as a kid, I didn’t even know this research career path was an option; people from where I’m from do not get PhDs, and they do not do research for a living. I thought that I would have to become a doctor in order to help people with migraine like me, and maybe I could be a compassionate doctor who could help.

Mandee Schaub

But I realized that I could probably have a lot more impact on the lives of headache patients if I was behind the scenes doing research. In order to get a PhD, I’ve learned, and in order to do research, you have to have an external driving force. The fact that I have constant pain – I still have huge migraine attacks that take me out of commission – really fired me up to do research. Understanding that there are other people who really need help, especially children, also motivates me – it’s really important to me to keep kids from having to suffer.

Let’s talk about your research. You’re studying a receptor called protease-activated receptor 2 (PAR2), and you recently presented some of that work in June at the American Headache Society (AHS) Annual Scientific Meeting. How did you get started on this project?

I’m a PhD student, so a lot of what I study comes from my mentors being really excited about something and hoping that someone will also get excited about it. I’m blessed to have awesome mentors, and they have been interested in PAR2 for a long time. My [principal investigator (PI), Greg Dussor, is a co-founder] of a small company called PARmedics, which is working on small molecule inhibitors of PAR2. Greg introduced this area to me and asked me if I would be interested in it.

So I looked into this receptor and I got really excited. One of the really interesting things about migraine is that different people have different triggers and different symptoms, and there are different kinds of headaches and types of pain that can arise from whatever starts the migraine cascade of events. PAR2 can do a number of different things, leading to a whole bunch of effects, and a lot of the molecular factors that we know have to do with migraine activate PAR2.

It’s really interesting to me that one receptor can do so much. That makes it hard to study, but it’s also really exciting, because it might be a key player in migraine. It’s a really promising target because of all the different things that it can be activated by and do.

What are your key findings so far?

I get to work with human dorsal root ganglion [DRG] neurons from organ donors, so we’re able to get fresh tissue that we can do some functional assays on. I use a technique called patch-clamp electrophysiology, and with that technique, I’ve been able to uncover that direct activation of PAR2 on human sensory neurons leads to hyperexcitability of those neurons.

That is interesting because hyperexcitability is a cell firing more action potentials, and more action potentials equals more pain. If we put the molecular factors that are released in the body during a migraine attack onto cells expressing PAR2, we get an increase in excitability of these cells, and that can be blocked with a small molecule PAR2 antagonist.

Where do you want to see this research go in the future?

I want to see these experiments repeated in human trigeminal ganglion neurons, which I’m really excited about and hope we’ll be able to start in the next few months. Trigeminal ganglion neurons are the most relevant migraine tissue; they innervate the dura, where it’s thought that the pain of migraine occurs. If we find the same hyperexcitability there as we found in the human DRG neurons, then it would indicate that blocking PAR2 in those neurons will also block nociceptive signals. That could be huge for migraine patients.

What I’m working on is small molecule antagonists for PAR2, and I’m hoping that one of them becomes a drug that we can administer to patients. There’s already a PAR2 monoclonal antibody in a phase 2 clinical trial, and we’re super excited about that, because this may be the successor to the CGRP story – we have monoclonal antibodies for CGRP, and small molecule antagonists for CGRP, and hopefully we’ll have a similar anti-PAR2 duo that works really well for patients.

Switching gears, let’s talk about your migraine advocacy work. Why did you decide to become an advocate?

People with migraine have been dismissed many, many times. I’m a pretty severe patient, but I don’t hold a candle to some of the people who I’ve met through my advocacy work whose lived experience is even worse than mine. They need someone to stand up for them with a loud voice and tell people what it’s really like to live with migraine. Because I am privileged to not be debilitated all the time by my disease, I feel like it is my job to stand up for the people who are.

Did you ever have any concerns, as an advocate, about sharing your experience with migraine when there’s so much stigma attached to it?

Yes, but because I feel like this is my calling, I’m able to put away the fear and try to be tough for the people who don’t have the option.

Why do you think there’s so much stigma directed against people with migraine? People who have migraine say they experience stigma even from their healthcare providers. Why would doctors stigmatize a person with migraine?

I think because they’ve never had migraine, or if they’ve had it, they had short attacks, not chronic migraine. I think that anybody who has experienced chronic migraine is not going to stigmatize patients.

I am 27 years old, and I have seen multiple neurologists and headache specialists. I’ve had almost every drug on the market. And six months ago, my neurologist told me that there was no way I had head pain every day – that it was not possible. I did my best to get out of that office, and I sat in my car, and I cried for all of the people who have migraine that this happens to. It’s 2025 – are we really still telling people that their pain is not real?

That blew me away, because I’m in this protected sphere where people believe that my disease is real, and I advocate with people who care about migraine, and I work with people who are working on the problem. But then, when I, as a patient and researcher, step outside of my bubble, I get stigma from my own doctor – it’s crazy. I’ve now found a better doctor, but stigma is still very, very real, and we have to fix it.

Do you think stigma results from healthcare providers not receiving enough education about migraine?

Certainly. We don’t do a great job of educating general neurologists or general care practitioners. It should be a requirement to know the basics of migraine care, and that should open up their hearts to not have the stigma.

We don’t do a good job of educating the people who aren’t in our circle. The same people go to the AHS meeting every year, and they already care about migraine, right? We’ve got to figure out how to get out of our bubble and educate and advocate outside of the people who already know about migraine.

What have your advocacy efforts looked like so far?

I get to be a Headache on the Hill representative – I’m actually wearing my Headache on the Hill sweatshirt right now. When Greg interviewed me for the PhD program here, he told me about a really cool program that he thought I should be a part of, and it was Headache on the Hill. The very first time I was eligible, after I started my PhD, he was able to send me to Washington, DC, for it. Headache on the Hill is a really interesting day where we get to talk with House and Senate members and explain what they can do to help people with migraine, at the level of the federal government. [See MSC related articles here and here.]

I was also able to lead a Headache on the Hill visual installment in Dallas. So this year in Washington, DC, the Alliance for Headache Disorders Advocacy and the Headache Alliance had flags cover the National Mall [see MSC related article]. We were able to do a pop-up installation here, too, on the UT Dallas campus, and hopefully it educated our general public – when I moved here and people asked me why, they had no idea that many of the best migraine researchers in the world were right here under their noses, and that we care a whole lot.

I will continue to advocate with Headache on the Hill, but I also talk about migraine as much as possible. So when I go to a doctor’s appointment, I talk about the things that I do for my migraines and the things that doctors can do. I went to urgent care for a headache treatment over the weekend, and I was able to tell them about the ways they can advocate for migraine. I also gave them a little education about what it’s like to live with it.

What is it like to speak to elected representatives? Do they listen? Are they interested?

I feel like everyone that I’ve spoken to so far has been interested. It’s a little nerve wracking, and it’s also difficult. I have a scientist’s brain, and I’ve been trained to have one, and I sometimes forget that they don’t know what I’m talking about because I’m using the wrong words. So I try to go in as a patient first and tell my story. I hate to pull on everyone’s emotions, but if they’ve never had a migraine, or if they don’t have a family member with migraine, then they don’t understand. You really have to bring them into your story and let them see what you’ve been through. But, as I said before, sometimes you have to put your fear away to help the people that you’re there to help.

You also have to tailor the asks to what they care about. So, for example, if you’re in the office of a representative who cares about the military, then you’re going to talk more about the Veterans Affairs ask. Or if you ask them if they have anyone in their family with migraine and they say yes, then you can talk about some of the challenges that their loved one has probably faced with insurance companies.

Let’s switch gears again one last time so people can get to know you even more. When you’re not doing science, what do you like to do?

I have a chocolate lab whom I adore. Her name is Doree. I love the Texas heat, so we go on walks. I recently started playing pickleball, and I rock climb – I love a little physical activity to help me stay calm, grounded, and normal. I also like arts and crafts, so I hand embroider and do watercolor painting; that’s one way I keep my creative side going. Sometimes you get in a rut with your science and feel stuck, so it’s really nice to step away for a moment and do some things that are creative and that allow you to grow. Then you can come back to the lab and usually have a clearer mindset about how to be creative there.

Another out-of-left-field question: If you could pick one scientist, alive or dead, in the migraine field or outside of the migraine field, to share a meal with, who would that be, why, and what would you talk about?

If it can be someone outside the migraine field, it would be [Nobel laureates] Erwin Neher and Bert Sakmann. They are the inventors of patch clamp electrophysiology. As passionate as I am about migraine science, I also love my technique. So I would really like to get to talk to them about how they came up with all of this, and about ways we can innovate the technology – it’s been the same for a really long time – to study migraine more effectively.

Two final questions. First, you recently joined the Migraine Science Collaborative editorial board as our trainee representative. You also convinced me that we needed an Instagram page, which you created and continue to propel. Why did you want to become involved with MSC? Why did you want to be on the editorial board?

It’s another way I can educate people about the research coming out of migraine labs. I also think it’s nice to have a patient perspective. So it’s another way to be involved in the community and help people as much as possible.

Finally, is there anything else you’d like to mention for people reading this interview?

If you don’t have migraine, but a family member or a loved one does, it’s really important that you give them a little bit of grace and compassion. Also, people who take care of you during a migraine attack, or who are part of your life when you’re going through it, can really have a huge impact on how debilitating your disease is. So love your loved ones with migraine.

Neil Andrews is a science journalist and executive editor of the Migraine Science Collaborative.

Image: Human DRG neurons at 90 days in vitro. Credit: Mandee Schaub.