Maya Adam: 

Welcome to Health Compass. I'm your host, Maya Adam, director of Health Media Innovation at Stanford Medicine.

Howard Chang: 

I remember that when I first met this person that my attendee told me that, oh, this is very typical that you have a woman with autoimmune disease. And because there's just such a strong sex bias and that set my mind, this really interesting question, why are autoimmune diseases so much more common in women compared to men?

Maya Adam: 

Today's conversation hits close to home for me. I'm speaking with two experts about autoimmune diseases and why women generally have to cope with them more than men. In my own extended family, we have a collection of autoimmune conditions including type one diabetes, vitiligo, and celiac disease. There are many diseases that fall under the autoimmune umbrella. And I had lots of questions for our two guests, Howard Chang, professor of Genetics and Dermatology, and Diana Dou, a postdoctoral scholar in Howard's lab. I spoke with Howard first and here's what he had to say. Howard, thank you so much for joining us

Howard Chang: 

Today. Thank you. I'm delighted to be here.

Maya Adam: 

Howard. Often in science, our professional careers are sort of motivated by a personal experience. I'd love to start if you're willing to share what brought you to medicine and specifically to the field that you're in.

Howard Chang: 

Yeah, so actually I came from a family of doctors. My father was a physician as with was my grandfather. And so I think growing up I was always thinking that medicine was a possible career path for me, but it was only when I was exposed to science, to laboratory based science when I was in college that I realized that maybe I want a career path that combines both scientific discovery and caring for patients.

Maya Adam:

Wonderful. Did you ever, along the way, that's a long path, did you ever have a moment where you doubted your decision?

Howard Chang: 

I think there was always questions for students about what's the right path. And also of course, anybody who was in the combined MD PHD training by definition is somebody who can make a decision, right? So you're always vacillating about should I put more emphasis here or there? But I was very fortunate that I felt like both my clinical interests and my research interests were coming together. And I knew I wanted to spend most of my time in the lab because I felt like in taking care of patients, oftentimes you'll realize you run to a situation where the patients come to the end of the road, we don't know anymore. We have no better options. And really to change that situation fundamentally we need more knowledge, we need more research.

Maya Adam: 

And why autoimmunity?

Howard Chang: 

Yes. So I actually had, I felt like a really important experience that when I was a medical resident in the field of dermatology, one of the clinics I look forward to is something called continuity clinic, where I would basically take care of let's say the same patients, but over and over again over a whole year. And one of the patients that I thought I learned really a tremendous amount from was a patient who had an autoimmune disease. She was an elderly woman who came down with an autoimmune disease and that had a number of complicated manifestations. So I learned I think many different aspects of how to use different medications, take care of side effects, all from trying to take care of her disease. But I remember that when I first met this person that my attending told me that, oh, this is very typical that you have a woman with autoimmune disease. And because there's just such a strong sex bias. And that sort of set my mind, this really interesting question is why are autoimmune disease so much more common in women compared to men?

Maya Adam: 

Howard, the idea or the physiology behind autoimmunity is kind of counterintuitive. So we have these immune systems that are meant to protect us, but sometimes they attack self cells. What do we know about why that happens?

Howard Chang: 

Absolutely. This is a fascinating question, right? So as you said, the immune system is amazing in the sense that it can protect us from all kinds of infections, something that body has never seen before, right? Basically we're talking about any kind of virus, any kind of bacteria, any kind of fungi, the immune system is ready to pick them, find these foreign invaders and combat them. But that capacity means that it's a system that is not pre-programmed. It's constantly also learning what is self, what is not self, what should it not attack. And that situation creates a possibility that there are cases where the new system makes a mistake, it goes after a normal tissue as self tissue thinking that somehow it's foreign and therefore it can attack it. And unfortunately, I think autoimmune disease is a situation where depending on where the immune system decides to attack, you can get many different kinds of manifestations. And that is why there are dozens of types of autoimmune diseases that affect almost 50 male Americans. So it is a significant problem.

Maya Adam: 

And can you give us some examples of cells that might get attacked and the diseases associated with them?

Howard Chang :

Of course. And so in my own field of dermatology, of course if you have an autoimmune disease against the skin, you might see rash, people would have red and scaly skin. Sometimes it's itching or painful. In a more severe situation, you might end up with blisters, skin starts peeling off. There are other situations where an attacks a very specific structure. For example, just hair follicles. So people with those diseases would have hair loss. So-called alopecia, and it could be either in patches or it just all the hair would fall out. So there are other situations where the immune system attacks pigment cells, and so those patients will look white as a piece of paper. So-called vitiligo. And so there are other situations where the immune system attacks the thyroid or attack the kidney. So it just depends on what tissue is being affected.

Maya Adam:

So interesting that you bring up those two examples because Howard, my mother who's dark skinned has vitiligo and I have a thyroid autoimmune condition. So my next question then of course is talk to me about the genetics of this.

Howard Chang: 

Right? And so what scientists have done, and also a clinician, is that if we look in families, we oftentimes see that there are certain diseases or symptoms that will run together. So there is a genetic component. And what people have found is that some of these autoimmune diseases are clustered. So exactly as you mentioned, one person in the family may have one kind of disease, another person in the family, they don't have exactly the same thing, but they have a related, it is still immune system based. And so this has led to an idea that there's a genetic set point that maybe the immune system is more active or less active. The immune system might start to attack this or that body part and therefore giving you different symptoms. But there's still the reflection of the same underlying sort of level of setpoint is either too active or not active enough.

Maya Adam: 

And Howard, of the 50 million people that you mentioned living with autoimmune diseases in the us, is it true that four out of five of them are women? And why is that?

Howard Chang: 

Yes, this is actually I think an astounding fact and really the focus of our research. So that number 80% or four out of five patients with autoimmune disease are women. That's actually just an average for a relatively common disease like lupus, that number is nine to one female to male. There's another disease called Sjogren's syndrome that is seen in dermatology that affects skin, but also some other tissues that disease is 19 to one female to male. So it's a really striking bias if you do any kind of population based study because of those skew numbers. Of course sex would jump to your number one difference as a important demographic factor.

Maya Adam: 

And can you tell me a little bit about why you think that's happening based on your fascinating research?

Howard Chang: 

Absolutely, yes. So this is a topic that the sex bias in autoimmune disease that many investigators have thought about for decades. So in the past, people thought about differences in hormones. So of course men and women have different sex hormones, men have higher testosterone, women have higher estrogen. So people study that sort of question from this angle for some time. But more recently, we and others started thinking that it's really more basic than that is more fundamental, has to do with basically chromosome counts. And so I should remind everybody that men or males have an X and a Y chromosome, whereas females have two x chromosomes. So a lot of evidence suggests that the property of having two x chromosomes that perhaps confers that risk. So that still leaves the question that a chromosome is basically a very long piece of DNA with hundreds of genes on there. So is it all those genes together, is it one of them on the second X chromosome that matters? And our most recent result research suggests that it's actually a single very special gene on the second X chromosome that encodes an RNA, that RNA, which is name exists, is perhaps a key driver in this female bias autoimmune disease.

Maya Adam: 

And I seem to remember from my biology lessons that the second X is sort of switched off or dormant. Is that true? And if so, how does that play a role?

Howard Chang: 

That is exactly right. So basically, so cells face a challenge that if you are born with an X and a Y chromosome, you have to somehow put out the same gene expression, genetic output as cells that were born two X chromosomes, right? So you start with different chromosome counts. So the strategy in mammals is that the second one of the two X chromosome in every female cell is shut down. So the chromosome is still there, but it's just not allowed to express gene activity. And that's actually done by this special RNA. That dimension called exist exists is only transcribed or made when salsa two x chromosomes is made from one of the two. And whatever chromosome is making exist, the exists RNA will shut down gene expression on that chromosome. And that's the reason how that men and women who have different chromosome compliments can have equal gene expression output.

Maya Adam: 

In the Stanford Medicine Magazine story exist is described as being in cahoots with other proteins. It recruits when it's doing its job of reducing the second X chromosomes output. But you found that the odd complexes of proteins and genetic material formed in the inactivation process can trigger a strong immune response. So is there a way to have sort of X chromosome inactivation without triggering other side effects? Is there a way for exists to sort of do its job without causing other problems?

Howard Chang:

Yeah, that's a great question. So let me explain why we think exists is so important. So as part of this, our exploration, we came to the idea that perhaps exists as a very immunogenic RNA protein particle. It would be female specific, and therefore it could explain this phenomenon. And I'm happy to explain how we came to this idea later. But the experiment that we did was to engineer male mice to express exist, which they would normally not do. And when male mice start to expressing exist, they start to experience female level autoimmune disease. So that really showed again that you don't need different sex hormones, you don't even need a second X chromosome, just this RNA and its protein partners is enough to give this disease. And so what we're thinking about what's going on is that in every female cell, there's exists sitting inside the nucleus of the cell trying to shut down the second gene X chromosome.

But when you mentioned when there's physiological stress, when there's damage, when cells die, that's when this exists. RNA will leak out into the blood and other cells, immune cells in the blood gets to see exists. And that's when we think the immune triggering happens. So to answer your question, I think that the way to stop this autoimmune problem but not affect the chromosome and gene expression is to focus on the exist molecules that are outside of cells. Because as normal job is inside the cell, inside the nucleus, it only causes problem when it's in the wrong location. So at least that's our current thinking.

Maya Adam: 

And you said you would take us back to how you had this idea. Can you tell us that story?

Howard Chang: 

Absolutely. Because I think looking back, this is one of the situation where my clinical world and my research will collide it, but hopefully in a positive way. And so my laboratory has been interested in the molecular biology of regulatory RNAs, including long noncoding RNAs that exist. And so I've explained that exist has this fascinating role that can shut down gene expression from a whole chromosome. So the research we had done led us to discover the set of proteins that exist. Work with exists is basically a little RNA recipe that assembles a set of enzymes to shut down gene expression. So we identify the entire set of exist associated proteins. There's 80 plus proteins there. So around the time when I was doing this research, my clinical world, as I mentioned, I'm a dermatologist, and in the US doctors have to take a test every 10 years.

So you have to take a test at the beginning to become a specialist to get a board certification. And the rules are that every 10 years you have to take basically a refresher test to make sure that you're still sharp. Okay. So as part of that process, I was basically studying and memorizing tests that are given to patients who are suspected to have autoimmune diseases. These are proteins that are so-called auto antigens. This is a situation where patients may have antibodies against one of their cell proteins. And if you have a situation like that, that protein where there are antibodies against it, that's an auto antigen. So I was memorizing these lists of auto antigens, which is going to be on the test. And then I realized that some of these protein names seem very familiar to me because they were the exact same proteins that we had pulled out as being associated with exist. So after a few of these examples, I decided to make a systematic list. And lo and behold, there's a large number of auto antigens that actually on the exist RNA protein particle. And that led to the idea that will perhaps then this exists RNA protein complex, it's this immunogenic female specific trigger.

Maya Adam: 

Interesting. So does that also tie in with the work around developing potential markers for autoimmune disease?

Howard Chang: 

Yes, absolutely. And so once we, we really mean Dr. Diana do who as a postdoc fellow did all the really hard work in my lab. Once we actually did the experiment showing that male mice expressing existed autoimmune disease, we started thinking about the diagnostic possibilities of this discovery. So I started by telling you that a number of the proteins associated with exist are auto antigens. And that lets to the question, well, what about the other proteins where people haven't looked? Why don't we look at all of 'em? And so we build such a device to look at auto antibodies against the entire set of associated proteins, and we found about almost 40 new sort of auto antibodies, new auto antigens that we're now developing to see if we can actually improve the diagnosis of autoimmune disease. So specifically what we discovered is that in several autoimmune diseases, and these are done together with clinical colleagues at Stanford that are large chunk Dr. David Tino, also with Dr. Dr Ami sha at Johns Hopkins, blood samples from autoimmune patients that they collected have elevated auto antibodies against parts of the exist complex that are not seen in healthy controls in general population. And so that is kind of, I think, a really interesting starting point to think about improving diagnosis for autoimmune diseases.

Maya Adam: 

So Howard, if for example, let's say as it is in my case, I have a lot of autoimmune diseases in my family, is there something someone like me should be doing in terms of my lifestyle that would somehow boost the chances that I narrowly escape any of these genetic gifts that I was given?

Howard Chang: 

Right? Yeah. So I would say that what we learned is that we know more about one of the drivers autoimmune disease, but a very important feature that we actually talked about already is actually this physiological stress. Because autoimmune disease, actually, even in our mice that are programmed to express exists, you have to have an episode of tissue damage and inflammation, a situation where cells die, these immunogenic molecules leak out. And without that, actually even these male mice expressing they can live a perfectly normal life, never having any problems. And of course, we know that every cell in a woman's body expresses has exists, but most women don't have autoimmune diseases. So I think that avoiding these episodes of stress, physiological stress, including avoiding viral infections, avoiding situation where there's tissue trauma, those are probably important things too. So taking care of your body, living a good life is probably the right thing to do.

Maya Adam: 

Howard, I'm curious about the one takeaway that you want to leave our audience with today. Is there a single one that you could name?

Howard Chang: 

I would say that why the immune system has a sex bias been a longstanding mystery, and we're starting to come to, I think, really a glimmer of why this happens on a molecular level.

Maya Adam:

Excellent. And my almost last question for you is, I know that the work you do is very time intensive and often stressful in itself. On the topic of avoiding stress, what is it fuels your passion and your commitment for the work that you're doing?

Howard Chang: 

Yeah, that's a great question. Well, I really have to commend actually Dr. Diana Dou who was doing this work because she showed a lot of dedication. It was a real hero in this story. And so as an example, this work was happening during the pandemic. And at one point, all the scientists were basically sent away from the lab, sent away from mouse colonies. Every lab was allowed to have one single scientist go into the mouse colony. She had many, many animals to take care of. She used to have an army of people helping her. But during that time, basically she was the only one allowed in. So she had a choice. She could either say, okay, well, I guess we can't carry on anymore, or she was going to have to do all the work by herself, and that's what she chose to do, right?

So right there, the project almost died, but she carried through. But I think for me, the reason for the persistence, of course, is that I think this is a very important problem. I mentioned my experience of taking care of patients of autoimmune diseases, and so it is really a striking sort of biological mystery that I felt more people needed to engage with. We learn also, I think a surprising or perhaps a glaring blind spot in the medical system. And that is that in the process of doing this work and understanding this female bias, understanding the role of exists in immunity, we wonder why was this not discovered much earlier? And so one of the things we learned was that there is a standard test that almost every person gets on the web being diagnosed with autoimmune disease. It's called an antinuclear antibody test, or a and a.

This is a test where you take blood from patients, you put the blood on some cells and you ask if the nucleus lights up or what kind of structure lights up. Basically what molecules can be recognized by antibodies in the patient's blood. And if that test is positive, that person has a possible autoimmune disease. And depending on the pattern of what lights up, there's different associations and people get sent down different diagnostic path. In that way, it's really the gateway test. And so that a test obviously is very common that millions of times a year. And so you might wonder, well, so people may have noticed that, hey, the exist RNA lights up or a structure associated with it lights up. Well, that didn't happen because in 1975, a reference cell line was chosen for doing the A NA test, and that was applied, I guess the issue worldwide.

And for whatever reason, in 1975, they chose a male cell line as a reference for the A NA. Okay, so let's think about what this means, right? So this mechanism I just talked about, it's female specific. If you use a male sound line that has an X and a Y chromosome, there's no second X chromosome, there's no exists. You'll never see anything related to exist. And so every year, millions of patients get that test. And let's be clear, most of 'em are women. So it's really a missed opportunity because the lab tests that we're doing did not match the physiology or the biology of the patient population we're trying to serve.

Maya Adam: 

Wow. Has that changed? Is there now a female cell line as the reference?

Howard Chang: 

Well, so we hope that the new test we develop where we actually just put, we can test all the exist associated proteins individually and very quantitatively. That is now the answer that you can actually measure these other antibodies in a very clear way.

Maya Adam: 

Absolutely. I'm so grateful to you for joining us today.

Howard Chang:

Thank you so much. It's my pleasure.

Maya Adam: 

I continued my discussion about autoimmunity with Dr. Diana Dou, a postdoctoral scholar in Howard Chang's lab. Diana, thanks so much for joining us.

Diana Dou:

Thank you for inviting me. I'm very excited to be here.

Maya Adam: 

Wonderful. Diana, I had such a great conversation with Dr. Chang about the discrepancy we see in rates of autoimmune disease between women and men, and I'd love to continue to explore that with you. But before we do, I have to tell you that Howard mentioned your heroic efforts to ensure the continuation of this research during the pandemic, and he said that that was something you did alone. So I wanted to ask you, what was that like? Can you tell us a bit about it?

Diana Dou: 

Definitely. I think what people don't understand about basic science research is that it takes a lot of time because we're literally not only on the cutting edge, we're trying to go beyond that into unexplored territory. So everything we try to do every single day, no matter how small the experiment is, something that hasn't been done before. So it hasn't been worked out. We're not sure if the method is correct. We're not sure if we even have the method available to do it. So sometimes we have to develop new methods or change the method a little bit so that it works with whatever we're trying to assess or whatever we're trying to test. So definitely when the pandemic hit and the project itself was already quite challenging, it was quite broad. There was many different approaches that we're using to answer, try to answer and investigate this very complex question.

So I have to admit, sometimes it was lonely and sometimes it was frustrating, but I really wanted to know the answer, so I just kept going. I think it's just keeping that goal in mind. And honestly, I felt a hypothesis that we had that exist, those particles will contribute to why females will experience more autoimmune risk than males do. I thought it was correct, but of course, you don't know until you go and you do the experience and you test it. So I had a lot of confidence in what I was doing, but I also was aware of the fact that maybe it's not, but that also would've been an interesting result. We just didn't know that the answer, whether it was yes or no. And so to me, that was one of the motivations. And also autoimmunity is just so poorly understood that I knew that just having any advance, even if the answer was like, oh, no, it isn't this, that would've been helpful to the broader community.

And I think most researchers go into science with the primary motivation of advancing knowledge and advancing science. And I think all of us kind of look up to Newton in a way where he said, if we see farther, it's because we stand on those shoulders of giants. And one of the things I love most about the scientific community is that we are part of a legacy, a continuing legacy. So everything that we find now is based on something that was found last year or in a different project, a continuation of somebody else's project, or even just hundreds of years ago, I think as soon as humans had any consciousness, we were asking why and how can we make this better? And so I think being a part of that is really historic.

Maya Adam: 

That's beautiful. Diana, back up for one minute. You were solely responsible for this entire lab throughout the pandemic. Can you paint the picture for us about how many animals you were looking after? What did your day look like? Just give us a sense of what that was like.

Diana Dou:

Yes, it was rather, it was an immense test because I would come twice a day, including weekends, because it was just not very much. If you were made essential for animals, you were essential for animals, and we want to make sure that their wellbeing is looked after. And so I would check everybody's animals. That was kind of my responsibility. And definitely in it was very strange to, first of all, I guess the benefit is that there was never any struggle for parking basically anywhere I wanted, but it really hits you how important it's to have people around you because science a lot of times is about communication and communicating through Zoom or virtually in lab meeting, it was very different than just being able to walk in the lab or walk outside and have lunch with someone and have discussions. And I think it is very, I think, kind of underappreciated how much of scientific progress is actually just driven by daily social interactions.

You could be talking to someone and they tell you something interesting and it kind of leads to something tangential, and then suddenly you're complaining about your project, how you can't get it to work. And then this person that you randomly just met up for coffee or at the coffee machine says, actually, someone in my lab is working on that. Or, wait, I know someone who works on that. And he's like, did you know this person is like, I did not know that person. And so these connections start to be made because again, what's wonderful really about Stanford is how everyone is so collegial. Everybody's willing to help each other. And so if they see that you're at Stanford, they also know that, oh yeah, no, they're probably doing something really cool. And they will also, they're part of the community. So there's a very strong sense of community within this campus that I just really appreciate.

As I understand when you're learning something new, when you're being trained, you will make mistakes. You will need multiple tries, and you will need to have a patient and understanding support system because it's going to be hard when things weren't working. And for a while nothing was working, everything, every method, even if it was established, had to be altered a little bit. And I had to figure out what the alteration was. Howard stayed very encouraging during it, and he also didn't hover, so he had a pretty good balance. So just like, okay, we just let her do her thing and if she needs help, she'll email me. And then each time I was like, I changed this. I think I'm getting closer. I'm getting closer. And so I'm hoping that I will also find that balance between being supportive and present, but also just giving people the freedom to learn what they need to and to develop into the scientists that they want to become.

Maya Adam: 

You talked about the power of having somebody encourage you to believe in yourself and to trust your judgment, right?

Diana Dou: 

Yeah. So Howard is great in doing that. I think he recruits people that he believes in, he believes are able to do this. And it's not necessarily, I think it's just my background was not in autoimmunity and it was not in Lin rna. My background was in hematopoietic stem cells. It was kind of a bit of a leap, but I mentioned it how in our meeting I was like, I'm interested in autoimmunity and I'm talking to you because I'm really interested in line of coding RNAs and I want to learn sequencing. I want to learn all these things I don't know how to do. And I think he just looked at the past track record and talk to my graduate advisor who was like, yeah, no, she will learn new things and she will keep working and she'll be persistent and she'll try to do the experiment as well as she can and be a scientist.

So I think the attitude is really important, I think both for the mentor and also for the trainee, because attitude is something that you can't really train and you can't really force. It just comes in. I think being in Howard's lab, having learned all these techniques and how to sequence and how to do the sequencing analysis. So I wasn't very computational at all until I came here. And eventually I was like, oh, if I want to know what is going on with these sequencing results, I can't just leave them in the files. I have to learn how to analyze this and processes. And so that was another adventure. So I think being in the Chang lab surrounded by all these really talented people who are all very busy doing really great science, you learn that attitude is maybe the most important thing in a scientist because I think that I can, and certainly Howard can train anyone to make a sequencing, library sequencing experiment or to analyze a dataset.

But what no one can really control is the attitude or the drive or the willingness to go and overcome all the different obstacles that you have to in optimizing the methods and the approaches and figuring out how to do the analysis, which is literally learning a different language. It's like a computer language and do this. So attitude I think is very important. And I was very, very fortunate to have Howard in his supportive role and his attitude because even when I would get a little bit discouraged, he would kind of remind me of like, but we found this. Remember Danny, this is experiment and this is it. Okay, if this isn't working, do you have any ideas of what else you might want to try? And I pitch sent him something. He's like, okay, yeah, no, let's try that. And if that doesn't work, then let's go back and revisit this one that you can't get to work quite yet. So

Maya Adam: 

Excellent. So the power of mentorship, I mean good mentorship that involves listening and encouraging the next generation of scientists to believe and to sort of trust their gut. That's very, very powerful stuff. Diana, I want to take you back just for one moment to the actual study. And I'm wondering, I find myself wondering why it's taken so long for this sex-based imbalance to sort of come to light. Why do you think that is?

Diana Dou: 

I find it, the more I think about it, the more astonishing it is. I'm shocked too. I'm not really sure. I think the funding or the maybe society wasn't really looking in that direction. And I think it's kind of a societal, because you can see how in just the past decade there's been a lot of advancement about promoting, protecting women's bodies and health and focusing on that. But I think it's just traditionally all doctors were male, and then all the anatomy was written on the male developed from the male body, and it's just kind of perpetuated. I think it was just a societal norm that bled into science, which is really, I guess not surprising because as scientists, we are still part of society. So there's this basic conditioning that everyone undergoes. And so I think you can really track how the movement has become more and more geared towards being aware of differences in individuals starting from just very early on or not very early on, but you can track progression of awareness in society.

And I think the greater society is what impacts changes in perception and also in policy and in law, because all of this research is supported by either private foundations. But for the large part, most of biomedical research is supported by the NIH and IH is also a branch of the government, and they are also impacted by political policies. And political policies are impacted by the people who are making those policies, who are elected through the voting base, so on the voting base society. And I think that brings up a great segue to emphasize how important it's to communicate science so that the majority of the population could understand and also understand that it's not going to be a quick fix. It's going to take time because these are complicated. Trust me, if we knew how to do this quickly, if we knew the answer and we could do it in a year or tomorrow, we would've done it yesterday.

But the human body is complex, individuals are complex, individuals are different. So solving this puzzle about, it's kind of miraculous how our bodies can develop and do all these things day to day that we just really just take for granted and understanding these small parts, small pieces, and to build this larger map, it takes a lot of people and it takes a lot of effort. And as I think I said before, it's all new. We don't understand it. We do it, but we don't understand how we're able to do this. And until we understand that, we're not really able to understand when things go wrong or how do things go wrong, where do things go wrong, what causes autoimmune disease when something goes wrong and what is going wrong in autoimmune disease? So I don't know. I think it's a long answer to say that I think science moves with society, and society right now is finally paying attention to women's health.

Maya Adam: 

Excellent. Well, this has been absolutely delightful. You're inspiring to talk to, I loved your enthusiasm and your explanations of how you see the work that you're doing, and I wish you all the best at Duke. Diana, thank you for making the time.

Diana Dou: 

Well, thank you for taking the time to interview. Me too. This was very fun. Thank you.

Maya Adam: 

You're welcome. It was such a pleasure speaking with Howard Chang and Diana Dou today. I really enjoyed asking them my questions about autoimmune disease and what it means to be a scientist at the cutting edge of this research. Thank you for listening to Stanford Medicine's Health Compass podcast. If you like what you heard today and you want to keep up with Health Compass, you can subscribe on Apple Podcasts, Spotify, the Stanford Medicine YouTube channel, or wherever you like to listen. Thanks so much for being with us today.