#NICHDResearch: Cori Cahoon, Ph.D.

While Cori Cahoon was growing up in Northern California, she had a hunch she might work in health or medicine one day. After all, her mother was a nurse, and her father was a veterinarian. Treating humans and animals was a core part of her nature and her nurture.

But she never imagined she’d spend her days studying worm sperm and eggs. Or that her cutting-edge genetic work on fertility could contribute to the future development of a male contraceptive.

Today, Cori Cahoon, Ph.D., is an NICHD-funded trainee, Jane Coffin Childs Fellow, and postdoctoral researcher at the University of Oregon 's Libuda Lab, which studies the genetics of and environmental influences on sperm and egg development. The lab looks at how sperm and egg cells are made, and how the genome is passed down from parental cells and preserved.

NICHD supports Dr. Cahoon’s work on the sex-specific temperature responses of developing sperm and egg cells. She wants to understand why sperm can’t tolerate heat the way eggs can. Broadly speaking, her research touches on the ways our warming world is affecting fertility and reproduction on a global scale.

“Infertility in men is a problem for couples trying to conceive,” she says. “With global temperatures rising due to climate change and heat waves becoming more common, the slowing reproduction levels we’re seeing in different species are affecting populations. And if populations can’t reproduce, it can have catastrophic ecological effects. This is why we’re trying to understand the heat sensitivity of sperm at the genetic level, so we can prevent these downstream events from happening.”

Heating Up

Researchers have known for decades that heat is detrimental to developing sperm in many species, from plants to humans. Dr. Cahoon’s work seeks to understand the mechanisms that cause this heat sensitivity.?

Dr. Cahoon is currently studying this in the soil-dwelling nematode C. elegans, a 1-millimeter-long worm. Worms, she says, are ideal subjects for this work because their sperm display the same heat sensitivity as that of humans. Plus, with worms, she can study egg and sperm development simultaneously.?(Side-by-side studies are harder to do with mammals because sperm are made continuously during an animal’s life, whereas egg formation starts in utero.)

Since Dr. Cahoon began the study in 2021, she’s found that a set of proteins involved in the regulation of DNA repair differs between the sexes. These proteins, which are highly conserved among species from plants to humans, are essential for fertility.

Based on these results, published in?eLife, she’s now trying to understand how these sex-specific differences affect the heat tolerance of developing eggs and sperm. A little over a year ago, she started a mutant screen—a way of purposefully creating changes in the DNA sequence—to identify proteins and mechanisms that make sperm more tolerant to heat. Once she understands these proteins, she can start to characterize what’s causing the heat sensitivity in developing sperm.

The Puzzle-Solver

Dr. Cahoon was raised near Sacramento, in the town of El Dorado Hills. Mindful of rising college costs, she began her higher education at a community college. A chemistry professor there told her that she had an analytical mind plus a knack for lab work. “I love the puzzle aspect of science,” Dr. Cahoon says, “where you don’t have all the pieces, and you’re trying to figure out how they fit together.”

When she transferred to the 美国加州大学戴维斯分校 , she tried different types of research. At first she worked with plants, studying how roots sense nutrients in the ground. But after the principal investigator moved the lab to Germany, she switched her focus to reproduction and worked as a research technician in Dr. Sean Burgess’ lab.

Dr. Cahoon’s initial work there focused on budding yeast—specifically, at the first steps of the yeast’s reproduction process. She soon realized that these steps are conserved from tiny single-celled organisms, such as yeast, all the way up to complex organisms, such as humans. What piqued her interest the most was how fertility is maintained through generations from parents to progeny. Dr. Cahoon wanted to use tools within genetics to understand the different problems that affect fertility.

“I’ve always been fascinated by genetics and how it works,” she said. “Studying yeast—in which you can directly visualize the segregation of chromosomes via genetic markers from parents to progeny—was amazing. I then wanted to understand exactly how that happened. What are the mechanisms that ensure DNA is inherited correctly?”

After Dr. Cahoon received her Bachelor of Science degree at UC Davis, she pursued a doctorate at the Stowers Graduate School in Kansas City, Missouri. Working in Dr. R. Scott Hawley’s lab at the Stowers Institute for Medical Research , she studied female fertility in fruit flies.

From there she went to Dr. Diana Libuda’s lab at the University of Oregon, where she has worked as a postdoctoral fellow since 2018.

The Niche-Finder

Today, Dr. Cahoon says she loves “being able to translate the research and what we do in a lab for a broad audience to understand. It’s a really important thing—and something that we as scientists sometimes forget.”

Dr. Cahoon applied for NICHD funding because it aligned with her niche interests within fertility. She found that the Fertility and Infertility Branch shared her research pursuits "in looking specifically at sperm development and how you make sperm."

NICHD funding via the NIH K99 Pathway to Independence Award has allowed her “the freedom to do exploratory-type studies, as not much is known about what happens to sperm following heat exposure. As far as the proteins that are being changed and the genes that are being modified, we don’t know what we’re going to get. It’s a high-risk, high-reward situation.”

Dr. Cahoon adds that she’s “grateful NICHD took a chance funding my research and allowing me to find the factors that are being influenced. Now I’m starting up my own research group looking at those proteins and starting to build a whole lab around it. The goal is to answer the question ‘Can we make sperm more temperature-tolerant?’”

“The broad question I want to understand is, ‘What are the mechanisms causing heat-induced infertility?’ For example: Protein A leads to Protein B leads to Protein C, and it causes a certain outcome. Once we know that whole pathway, we can start to manipulate it, so that now Protein A leads to Protein D leads to Protein C. And eventually, you have heat tolerance.”

Dr. Cahoon is also expanding her research beyond invertebrates. In a non-NICHD study, she and her colleagues are investigating whether sperm proteins are regulated differently in zebrafish, which still have the same consequences temperature-wise.

“The long-term goal is to get a really complete picture of all the different ways that you can cause temperature sensitivity in sperm,” she says.

Soon, Dr. Cahoon will work toward that long-term goal in a new setting. Starting in January 2025, she’ll be an assistant professor at Colorado State University (CSU).

It’s a move that demonstrates how impactful NICHD support can be. The NICHD Career Transition Award that Dr. Cahoon received in 2022 is intended to help recipients start their own research groups and take the next steps in their careers.

“Getting this faculty position at CSU shows that, in my case, the transition award was successful,” says Dr. Cahoon.

Running, Singing, and the Power of Persistence

An avid runner, Dr. Cahoon regularly competes in marathons and half-marathons. Being in motion, she says, “clears my head and clears my stress.”

When she’s not working, running, or walking her pug, Lucy, she’s often attending theatre shows.

“I love to go to the theatre,” Dr. Cahoon says. “I’m huge fan of Broadway and the touring Broadway shows. Every year, my mom and I travel and check out a series of them.”

Meanwhile, Dr. Cahoon has a few words of wisdom for younger trainees and up-and-coming scientists considering a career in research.

?“Keep asking questions,” she said. “Keep being curious about whatever it is that you’re studying. Because you never know what the answer might be and where it will take you on your career path.”

She said that she’s a perfect example of this principle.

“I started off studying chromosome pairing in infertility and thought it was the coolest thing ever,” she said. “And now I am studying environmental influences on fertility—what outside influences are directly impacting fertility, beyond the genes themselves—which was based on pure curiosity-driven research. I just came in and asked questions and kept marching down the path. As soon as I would get an answer, it would lead to another question.”

“Science doesn’t always work,” said Dr. Cahoon. “But if you’re persistent enough, usually you get some sort of a breakthrough—even if it’s not what you expected. Just keep being curious. Be persistent.”