Episode 14: Tulane Center of Excellence in Sex-Based Biology and Medicine with Key Opinion Leader Franck Mauvais-Jarvis

You're listening to BIO From the Bayou, featuring stories and industry insights from experts in the bustling biotech scene of New Orleans. The entire Gulf Coast region is buzzing with expertise and excitement, and we're here to bring you frontline access to this vibrant ecosystem direct from NOLA, the city that provides a little Lagniappe with everything we do. Where people come for the science and stay for the food, festivals, and resilient culture. I'm Sharon Courtney, Vice President for Government and Community Relations at Tulane University. And I'm Nicole Honoré, Assistant Vice Chancellor for Economic Development and Strategic Initiatives at LSU Health New Orleans. And this is Bio from the Bayou.

Hi, welcome back to Bio from the Bayou. My name is Dr. Elaine Hamm, and I'm the Executive in Residence for the Tulane School of Medicine. And today's guest is Dr. Frank Movistarbes, who is a professor of medicine at the Tulane University School of Medicine and is the director of the Tulane Center of Excellence in Sex-Based Thank you so much for joining me today.

Thank you for having me.

Great. Well, so in my role of drug development, patient diversity is becoming a really important topic because we need to better understand how all patients will respond to a particular drug, because understanding those differences are really key to helping us conduct the best risk assessments and to really design safer and more effective treatments for a variety of patient populations. And Those differences can be things like race, differences in age, but also differences in sex, because all of those things can really impact how a patient is going to respond to a drug. And we're talking about sex differences in this context. We're not talking about gender, but rather the physiological differences, because we know that males and females respond differently to drug treatments. And, and even subpopulations of pregnant versus non-pregnant and menopausal versus premenopausal women, all of these physiological differences can have an impact on how a patient will metabolize And respond to a drug, and it's a very important topic. So with that in mind, I'm very excited to talk to you about this topic today and learn more about your research. So diving in, I would love to understand what inspired you to create a center of excellence around sex-based biology and medicine.

Well, you know, there are major differences between men and women in biology and health, and I'm not speaking about the reproductive organ, I'm speaking about everything. And regarding disease, there are also major differences in all diseases between men and women in terms of mechanisms, evolution, response to treatment. So for example, if you— if a disease is less prevalent in a woman than in a man, and if you can harness the biological forces that protect one sex compared to the other, then you have a therapeutic avenue for precision medicine. So I think it is studying differences, sex differences in disease is really, really a foundation of precision medicine. So I wanted to create this center for these reasons and because I think it is the future of the new frontier in medicine.

And so are there other sex-based biology centers in the, in the US?

Yes, there are no other centers in the South where we are, but there are several other centers that are funded by the National Institutes of Health, and especially one of its subsections, the Office of Women's Health Research. They are called Specialized Centers of Research on Sex Differences. They are focused on a specific disease like metabolic disease, Alzheimer's, cardiovascular disease.

And that's great. That leads me to another question. You know, what sex-based gaps in diabetes and obesity research is your work specifically trying to address? Because you mentioned metabolism obviously can have a big Sex differences can have a big impact on that.

Well, I am an endocrinologist, so one of my major focus clinically is to treat menopausal women who lack estrogens and older men with testosterone deficiency. But apart from that, we are working on the effect of estrogen and androgen in women and men respectively and how it improves metabolism. And, you know, estrogen receptors and androgen receptors are very well-characterized drug targets, very well studied by the pharmaceutical industry. So if we can understand how activation of these receptors protect from metabolic disease in a sex-specific manner, then we have opportunities again for sex-based precision medicine of metabolic disease.

No, and that's something that you and I have discussed, especially as it relates to estrogen. One of my own companies is looking at the difference of women that are pregnant and how they have remission in MS and being able to take advantage of that and design a drug that can exploit that. And so understanding the estrogen receptors can be really helpful in addressing a number of diseases. So really fascinating work that you're doing. And so when you're looking at diabetes and obesity, Are there things that you take into consideration as you're designing different experiments to address those issues?

Well, like I said, for example, let's take the example of female women— saying female because we're studying animals also. So we're studying the effect— the effect of estrogens in animals is very, very powerful in terms of protecting from diabetes and obesity. So we have to separate the males and the females. And especially study them separately because a lot of investigators, you know, are pulling them together and the results are absolutely non-relevant. Yeah.

And I think that, I mean, what can other universities and researchers do to better address those types of issues in their own research? You mentioned, you know, being able to separate when we're looking at animal models, being able to separate the males and female mice in the study just so you can understand if there's differences or not that as it relates to the physiological responses, but are there other types of maybe non-animal models that you're looking at that can also take those things into consideration as well? And what types of tools should scientists be looking into?

Well, if you take clinical research, the NIH has mandated a long time ago, I think it was in 1993, by an act of Congress, that women be included in clinical research. Historically, they were not included for the purpose of protecting pregnant women. But now they are included. But the problem is that a lot of investigators, even if they follow these guidelines, they do not stratify the results by sex. And therefore, because men and women are clearly 2 different populations, the results are not reliable. Let me give you an example. If you pool the male and the female together, for example, and you see no No effect of a new drug. Well, by stratifying the result by sex, you may see an effect on one sex and not the other. But if you pull them together, the significance disappears. We see that every day.

Yeah. And you miss out on opportunities by not taking stratification into your research, for sure. Yeah.

Yes.

So how can companies and foundations that are interested in sex-based precision medicine engage with the center, engage with professors such as you that are looking into this type of biology and subset of medicine?

Well, you know, it depends on what kind of product they are interested in, what kind of device or what kind of drugs they are developing and what they want to do. But the first thing they should do is contact me so that I can orient them towards who can work with them. But definitely, if they're interested in philanthropy, they should contact me.

Great. And are there other tools? And for example, are there cell lines that can also help address Are we looking at, in the early, early stages of research, of taking those different types of physiological differences into account? Or are we not there yet?

This is an important question. And I think we talked about that, is that, you know, the cell line that we use, we have to create clonal cell lines. That means they are genetically engineered, you know, to be maintained through several passage generations. And we can, for increase them. But the problem is that you don't have a male and female cell line for any kind of tissue and any kind of species on the same genetic background. It doesn't exist. So you cannot compare male and female in cell culture. So this is something that needs to be engineered, you know?

Right. Is that something that you guys are working on or other groups are working on?

We're not working on that, but I think some groups are working on that from embryonic stem cells.

Oh, interesting. Yeah. And so kind of in line with that, where do you see your field going in the next few years?

Well, I hope that people will realize how important it is to appropriately consider sex in the design of research and to consider that male and female, men and women, are, like I said, different patient populations. Okay. And I think right now a lot of people are not doing that Entirely for multiple reasons. But it is, like I said at the beginning, it is a new frontier. So the field needs to evolve to really, really dissect the differences between male and female in biology. Because again, the biological forces that protect one sex compared to the other are therapeutic targets that are hidden in plain sight. One of the advantages of the center that we have at Tulane is that unlike several centers that exist in the country that are very focused on a specific aspect of sex differences, our center focuses on everything. There are multiple investigators and they study a lot of different kinds of disease, but also we tackle the problem from a transdisciplinary approach. So we have basic researchers, we have bioengineers, we have clinical researchers, we have epidemiologists, and we even have people working on social sciences. So this kind of transdisciplinary approach of convergence research, I think, will help generate novel ideas.

Yeah, that transdisciplinary aspect is really important. So how do you see Tulane and your center in particular making an impact on this field of research in addition to the transdisciplinary approach?

Well, the first impact is that we need to be funded by the National Institutes of Health. You know, if you have the stamp of the US government, that helps philanthropy. So we have applied for a COBRE, a Center of Biomedical Research Excellence, to study that and to help junior investigators being funded into this area. But another way that I think we're going to make an impact is that we have developed a curriculum to train the next generation of student researchers and of medical students into the principles of sex-based biology and medicine, as well as the methods to study that or to see patients under a different eye, you know.

That's a really interesting aspect. I mean, a lot of times when we talk about sex differences. We're speaking more about research and drug development, but it obviously impacts how a physician would treat a particular patient based on the physiological differences that they may have, whether it's race or sex differences. I really appreciate the transdisciplinary approach and that you're training the next generation as well. Fantastic.

The clinical approach, in fact, is complicated because it involves an understanding of sex differences, biological sex, but also gender differences, social constructs. Let me take an example, example of heart attack, myocardial infarctions. People think that only men have myocardial infarction and that women are protected, but heart disease is still the first cause of death in women.

Yeah.

And there are multiple studies that show that when women are admitted to the emergency room with an ongoing myocardial infarction, they are more likely to be discharged and to die, even if they are treated by a female physician, because the pain is different, which is due to biology. It's more of a disease of small vessels, but also because of social constructs, because we believe that women are protected, that they shouldn't have a heart attack. So, you know, it's always an interaction between biology and gender.

Yeah, I think when we think about diseases for women, we automatically think breast cancer, but really cardiovascular disease is a huge killer of women every year. Women are very good at dismissing some of our symptoms. So taking our own health into consideration, but also training, as you say, the next generation of doctors to really think about when a patient presents with certain symptoms, to really dissect what that can really mean, can really save lives. So that's really incredible. Another question I have is just where do you feel like the whole field as a whole is going? Where's like the cutting-edge aspect that you see? Or where, maybe asking a different question, where do you see the biggest challenges ahead?

Well, the biggest challenges— there are multiple challenges, but it will really be to design drugs that have a different effect in male and female, even if it's the same drugs. In terms of organ transplantation, there will also be a lot of challenges because sex differences are not only to circulating hormones. Men and women, they have different sex chromosomes. So, and these sex chromosomes change the entire gene expression of a cell. So let's say when you transplant an organ of a male into a female, it's not the same thing that if you transplanted a female organ into a female individual. So this is, I think, going to be a— and people don't think about that— this is going to be a major challenge. Wow.

I hadn't thought about that, about differences as it relates to organ transplant. Do they stratify patients based on that? Do they take sex differences into consideration?

They don't do it right now, but I collaborated with a good group of transplant surgeons at University of Miami who were transplanting pancreatic islets, you know, to improve type 1 diabetes. And they contacted me to help them look at sex differences. And what we found is that when you transplant female islets into male and female type 1 diabetic patients, the results which is calculated as the number of years that the patient remains insulin independent, the result is much better when you transplant female islets than male islets. Wow.

Wow. That's fascinating. I didn't realize that.

I assume that it should be the same in other organ transplantation, but it still needs to be, to be seen.

It touches on a number of different aspects as it relates to health, not just drug development, but organ transplants, patient care, and And how we think about our own health. I probably need to reevaluate my cardiovascular disease status myself, but I'm very pleased to have this conversation with you. It's such a fascinating and really, really important topic that I don't think that we're talking enough about in my industry, certainly, but in a number of aspects of healthcare. So I'm excited to see what your center will do in the future, and thank you so much for joining us.

Thank you for having me.

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