Bringing female physiology into the spotlight: A conversation with Holly A. Ingraham, PhD
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Key takeaways:
- Ingraham studies basic molecular processes in endocrinology with a recent interest in sex bias in women.
- Ingraham stresses the importance of diverse mindsets in science.
CHICAGO — From a curious child playing with a microscope to molecular physiology professor, Holly A. Ingraham, PhD, leads a career in molecular processes with a recent focus on how endocrine signals shape female physiology.
In addition to her research focus on female physiology in endocrinology, Ingraham also runs programs to help underrepresented postdocs, with the aim of making her field more inclusive.
“Inclusion is many things. It’s how you attack science based on your interests, where you come from, your socioeconomic point of view, etc. — it can mean so many different things,” Ingraham, the Herzstein Endowed Professor in molecular physiology at the University of California, San Francisco, told Healio. “The more inclusive we are in this process, the more progress we will make.”
Ingraham is the most recent recipient of the Edwin B. Astwood Award for Outstanding Research in Basic Science from the Endocrine Society presented at ENDO 2023. She is honored for her significant contributions to endocrinology, including illuminating basic molecular processes controlling endocrine development and physiology with an emphasis on understanding the cellular and molecular basis of diseases with sex bias in women.
Healio: What was the defining moment that led you to your field? Why do you do what you do?
Ingraham: There were two things in my youth that got me into science. One was my high school biology teacher who introduced me to DNA. I was fascinated by that discovery, only to learn later that a woman, Rosalind Franklin, was left off the Nobel Prize for achievement. The other fortuitous event is that my great-grandfather (the only academic person in our family) had his 1890 Bausch & Lomb microscope. I found it hidden in the closet. After unlocking it, I started looking. It’s a beautiful microscope. In hindsight, it was also fortunate that my parents weren’t helicopter parents giving me the freedom to explore my surroundings inside and out, follow my curiosity and make some mistakes along the way.
Healio: What area of research in endocrinology most interests you right now and why?
Ingraham: I’m most interested in how female physiology is sculpted by hormone signaling in the brain and peripheral tissues. As a basic scientist, I work in the lab with mice, not people. For decades, labs have focused on male rather than female animals because females were thought to be too complicated due to fluctuating hormones during their estrous cycle. We are learning that there is much to be mined regarding what happens during these fluctuations, which are essential for species’ survival. We ca also learn much by understanding what happens during aging when there is a natural decay in hormones. Pursuing this line of research will undoubtedly impact women’s health.
I’ve always been focused on mechanisms and like understanding how things work.
Currently, the most exciting questions for me aim to uncover sex- specific brain pathways governing female metabolic and skeletal health.
This research was neglected for so long because those working in the brain rarely ventured into peripheral tissues and vice versa. I’m trying to recruit younger scientists to work in these large wide-open areas, especially younger women scientists. I am convinced that working on the basic science underlying female physiology will offer insights into curing insidious diseases that primarily affect women, such as polycystic ovary syndrome, endometriosis and irritable bowel syndrome. These disorders affect millions of young women, and yet we don’t know much about them at a basic level. On the other end of the spectrum, after menopause, why does metabolic health decline without estrogen? Why do our bones degrade? Why do women have osteoporosis much more than men? Why do we suffer from dementia and neurocognitive disorders at a much higher rate? I often mention in seminars that women live longer but age much more poorly. Many of these diseases affect the quality of life for millions of women and breast cancer survivors who experience premature menopause because they take anti-hormone therapies.
Just think about the work required to tackle sex bias diseases in females. It’s huge. At a national level, we still don’t have enough resources or scientists to investigate these diseases at a mechanistic level. That’s what I’m intrigued about right now and that’s what I’m spending my time doing. My goal is to raise awareness of these issues through science.
Healio: What do you think will have the greatest influence on your field in the next 10 years?
Ingraham: There was a time when everybody said that males and females have the same physiology. That can’t possibly be true. For example, men store fat around their bellies while women store fat subcutaneously until menopause. For females, these differences have evolved to sustain progeny in utero and after in the postpartum period —fundamental sex differences in male and females physiology. And while we have known for decades that there are notable sex biases in disease prevalence it is only now that we and others are actively seeking answers to explain these sex differences.
I hope that in the next 10 years, more and more studies will emerge in this area. I’m also hoping that technologies needed to identify interesting circulating molecules, which are hormones, improve so we can detect low abundant circulating hormone factors that profoundly affect our physiology. We’re still not there regarding technology, but I’m hoping that can occur in the next 10 years.
Healio: If you weren’t a physician and/or researcher, what would you be doing?
Ingraham: I would have been a landscape architect because I love gardening and I love thinking about how to put plans together and the challenge of plants. They’re very dynamic. They grow, you must trim them, they die, you have to pull them out and weeds spring up, so you have to deal with that. It’s a very dynamic process. I really love doing that. The other thing that I probably would have been is a computer geek doing programming. If I had been younger and I didn’t go into biology, I might have gone into computer programming.
But I love physiology and I would never get that doing computer work. One thing I will say as an older person who has been in this business for 3 decades is that I still feel that the best discoveries are going to come from hypothesis-driven questions, not from large data surveys. That approach has its place, but fundamentally, I think that discoveries are hypothesis-driven. You’re in the lab and you notice something, and it seems out of the ordinary, so you pursue it. That’s never going to go away in science. I like hypothesis-driven questions a lot.
Healio: Who are you outside of your job? What interests you outside of endocrinology?
Ingraham: I run programs to help postdocs, especially women and underrepresented postdocs, with their career progression and trajectory and providing some of the soft skills they need to stay engaged in science. Academic science is hard. There’s no doubt about it. It’s so thrilling, but it’s so hard because you’re always fighting to get money and you’re constantly questioning yourself. I’m passionate about that. I just received the UCSF Lifetime Achievement in Mentoring Award for helping younger faculty and younger postdocs. My passion for doing that is from going through a field that was a bit non-inclusive with feeling like you had to be part of a club to be part of that field. I decided I wasn’t going to follow the boys anymore; I was going to do my own thing. I also decided at the same time to challenge leadership in terms of looking at the number of women in these positions and try to be more inclusive. I’m not just talking about racial diversity, but I’m talking about the way people think. Including more diverse thoughts in science is going to accelerate science. I am very passionate about that outside of what I do in terms of endocrinology.
Healio: Whom do you admire and what would you ask that person if you had 5 minutes them?
Ingraham: There are so many great scientists that have come through and done amazing work in endocrinology. The early people that were discovering some of these systems, I just read some of those papers and wondered how they figured a lot of this stuff out without any of the tools that we have now. I’m always amazed at that. It’d be fun to go back in time by 100 years and ask these scientists how they discovered some of the main staples of this business, which is how these hormones communicate with different organs and what the impact of these hormones were on physiology.
Other people I enjoy talking to that I would like 5 minutes with are younger trainees who decided they’re going to go into endocrinology. They have this curiosity that they want to follow. How did they figure out how to get into this business? How did they acquire that resiliency? I love to find out from individuals how they got to where they are and how they got into this business.
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