Episode 39: Exploring Sex-Differences in Physiology with Key Opinion Leader Heddwen Brooks (RE-RELEASE)

Our meeting schedule at BIO 2024 was packed, so if you missed meeting with Dr. Hedwynne Brooks, check out our fan favorite episode of 2023 when she discusses her captivating research into sex-based medicine and women's health.

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Welcome back to Bio from the Bayou. Today's guest is Dr. Hedwynne Brooks. Dr. Brooks is a professor of physiology at Tulane University School of Medicine and is our chair of the Department of Physiology. Welcome, Hedwynne.

Thank you. Thank you for inviting me.

Well, you have recently taken on the position as the chair of physiology at the Tulane School of Medicine. I was curious what some of the scientific strengths that you see in your department, what really enticed you to come here? And particularly, I'd like you to talk about ones that external collaborators might be interested in— companies, investors, foundations, things like that— so they understand areas where they should approach you for collaborations or to find a key opinion leader or to engage in any way.

Great question. One of the strengths, or the real strength that enticed me to Tulane, was the historical and International reputation of the Department of Physiology, but also Tulane School of Medicine in the area of hypertension, kidney disease, and looking at how kidney disease is important in diseases such as diabetes. Specifically for the department, we have a real strength in sex differences and women's health, and that's an area that I research myself, but within the department, we're taking that to a different level. We're looking at menopause and aging in females and looking at it in the terms of not just how that happens with the loss of estrogen, but also how that impacts your brain function, your kidney function, how it makes you more prone to diabetes or high blood pressure.

So you've mentioned sex differences as that key thread in some of the research being performed, and I know that's not just in your department, but in other departments at Tulane as well and other colleges. Why is it so important to study sex differences in general in science?

Well, until about 20 years ago, nobody was really looking at the difference in sexes in diseases. We tended to focus on males. Males were included in clinical trials, and if women were included, the data was pooled. So you couldn't see if there was a difference between the men and women. And recently, the NIH, the National Institutes of Health, came out with a mandate that people needed to start looking at both males and females in preclinical and clinical. And the reason for that is most physiological processes, even in the brain, the kidney, the heart, have a different impact and a different process of how they deal with things. So it's very important to look at either males or females and not to pool the data.

Are there reasons in particular for, say, hypertension and diabetes that you need to study sex differences?

Absolutely. So women have a lower blood pressure than men. Until they hit menopause. And menopause is the time when women's ovaries start to fail. We lose estrogen. And that is on average about 51 years old. So it's not an old age, it's sort of accelerated aging past menopause. So until that point, our blood pressure is lower than men, and then it accelerates. And that is the definition of hypertension, is when your blood pressure goes above healthy. And so what we don't understand is why, or the process of how it gets worse and worse, and more importantly, why the drugs don't work as well in women. All the drugs, again, have been developed in clinical trials with men. So why don't they work as well? And that's really a key question.

So what are the advantages in studying hypertension from a renal physiology standpoint?

Well, the kidney controls your blood pressure, right? Every single drug that you take to lower your blood pressure will make you urinate more. And that's because the only way to lower your blood volume is to excrete it. So every drug you take initially will usually make you lower your volume by excreting more urine.

So, Dr. Brooks, I believe you've been working on some new lines of research in your department and some of your own personal research as well. And as I recall, maybe it relates to immunology. Is that correct?

Correct. Yes. So we're looking at how the immune system changes as women go through menopause. We know that once women are in menopause, they tend to have more inflammatory markers in their blood. They are more prone to inflammatory diseases like diabetes and hypertension. So we're really trying to understand what the role of the immune system is in the development of disease after menopause.

So now that we've talked about both sex differences in immunology, something came to mind that you mentioned to me once. It's that during the pandemic, there was a distinct difference in how COVID affected people based on their sex. Could you talk a little bit about that?

Yes. So it was interesting that COVID actually was more severe in men than it was in women and actually caused, I think, 3 times more deaths in men, even at the same age. So women definitely had some protective mechanism against disease and death during COVID And as we know, you know, that's an immunological feature. So there's a lot of fantastic research going on across the country and here at Tulane Trying to understand what was protective in females. Was it some kind of change in cytokine storm that the females didn't have that caused a lot of the damage in the men? So yes, COVID highlighted the importance of sex differences in our research.

And so one question that I hadn't prepared in advance, but I would love to ask, 'cause I feel like we left it out. Are there some people in your department you'd love to highlight with some of the research they have going on? Any particular faculty that are working on interesting projects?

Yes, Dr. Zombach is working on the role of Alzheimer's in women. So women after menopause are 3 or 4 times more likely to get Alzheimer's than men. And she's really looking at how obesity and metabolic syndrome impact the progression and onset of Alzheimer's in women. So once you go into menopause, you're more likely to get diabetes, your cholesterol levels go up if you don't take estrogen. And then on top of that, if you've got Alzheimer's, it might progress faster. Or we don't know. And she's really doing some preclinical work on that in collaboration with a new program project grant that the School of Medicine got, combining the Center Brain Institute and Physiology and Pharmacology. So that's a real key area. Another person I'd like to highlight is Dr. Ryo Sato. He is developing technology that uses cells and he grows the kidney out of these cells. They're called organoids. And that means that you no longer have to use mammalian models, but you can use them to screen drug targets. And he can implant them under the kidney capsule so that they get a blood flow from the host. And this is really something that's going to develop more and more as we try and get away from using the rodent models and really try and do drug screening in an in vitro model that receives the host cells, immune cells, and things like that. So that's a really exciting area.

And so I guess in closing, I would love to ask what advice you would give to scientists who are interested in incorporating sex differences into their studies, or companies who are interested in that for their product lines. What should they be thinking of? Who can they come to for advice?

That's great. Well, they're welcome to reach out to our department. My own research actually uses a translational model of menopause that retains the ovaries. So it's a highly important model that people across the country and the world are now using. because you can intervene, and it has a perimenopause phase, which is the time between when you are still cycling as a woman and when you actually stop cycling and your ovaries have failed. And that's a really important time where interventions can be targeted to try and prevent the accelerated aging that happens. So we are— we welcome collaborations using that. It's called a VCD mouse model of menopause. And also, I think, Just reach out to people in your institution who are doing it well and make sure that you check with them what the parameters you need to study.

That's really great advice. And I want to thank you for joining us once again. It was fantastic to have you on today, and we look forward to having you back on sometime in the future. And I know Dr. Hamm, one of our other hosts and our executive in residence, is really interested in talking about your work to increase gender diversity in the scientific profession. So maybe you and she could have a chat about that sometime soon.

I would love to.

As always, we will have Dr. Brooks' contact info and some informational links posted in our show notes. We'll also include some info on Dr. Zombach, Dr. Sato, and Dr. Brooks' own work. So make sure you check out our show notes to learn more. And if you're listening to this at BIO 2023, Dr. Brooks is part of our partnering team. We'd love to set up a one-to-one meeting with you and her. Please reach out.

Thank you.

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