Judith Simcox can trace the course of her research career all the way back to high school. Her class was given an assignment to explore a question about the world around them. Most students posed somewhat conventional queries: Why is the sky blue? or Why are animals going extinct? But Simcox’s question was far more particular: Why do people with Down syndrome have elevated rates of type 1 diabetes?

It was a highly personal inquiry for Simcox, one that stemmed from her family’s own circumstances. Her mom, a nurse, worked with the Special Olympics team where her younger sister, Jan, was a member. Jan was born with Down syndrome and developed type 1 diabetes in elementary school. At the time, Simcox simply found this to be unfair. She later discovered that, of the 12 people with Down syndrome on her sister’s team, four of them also had type 1 diabetes.

Those numbers stuck with her, and she jumped at the chance in high school to find out more about the connection between the diagnoses. Simcox learned that 4% of people with Down syndrome are diagnosed with type 1 diabetes. That’s compared to just 0.5% of people in the general population.

“It was a major difference,” recalls Simcox, who is now an assistant professor of biochemistry. “But I also found out that no one knew why they have these high rates. It was the first time I had asked a science question that didn’t have an answer.”

Her curiosity about metabolic disease in diverse populations also began with personal experience growing up in a rural town next to the Crow Reservation in Montana, where her friends and family live. All of her aunts and uncles struggled with complications from type 2 diabetes or cardiovascular disease. Simcox carried her interest to Carroll College, a small liberal arts school in Helena, where she intended to follow in her mother’s footsteps and study nursing. But her plans changed.

For one of her classes, she was required to attend a science seminar. Simcox chose a talk about evolution and ecosystems by a professor named Gerald Shields. Afterward, she peppered him with questions.

“I basically cornered him for 20 minutes,” she says with a laugh. “Luckily, he said, ‘You should come and answer all your questions in my lab.’ I ended up working with him for four years, and he opened up the world of science to me in so many ways.”

Again, Simcox’s questions had spawned new ideas and possibilities. They would lead her through college as well as a Ph.D. program and postdoctoral training at the University of Utah. It was there that she dove into metabolism research, studying diabetes and cardiovascular disease, and began to address the questions she first raised as a high school student. She continues finding answers at UW–Madison. Since joining the Department of Biochemistry in 2019, she has built an impressive team of five graduate students, three postdoctoral fellows, and two faculty collaborators.

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The main interests of Simcox’s lab are metabolism, lipids, and biomarkers. Biomarkers, or biological markers, are substances or processes in the body that can be objectively measured and used to predict the occurrence of disease. Simcox and her colleagues aim to discover how different markers perform for different populations throughout the world, including Black populations, Native American populations, people with type 1 diabetes, and people with disabilities. The most commonly used markers to determine diabetes risk are lipids, energy-giving fat molecules that circulate in the blood, such as LDL and HDL cholesterol and triglycerides.

“The negative thing about these markers is that they were developed in an all-white population of Western European descent,” explains Simcox, who is also an affiliate in the Department of Nutritional Sciences. “We have known since the ’90s that these markers don’t predict cardiovascular disease in diverse populations, specifically in Black populations. This means they’re not getting the same standard of care.”

This problem led Simcox to ask another round of ambitious questions: Why hadn’t this disparity been addressed yet? How could better markers of disease in all populations be identified? She and her team look for previously unidentified markers by identifying and separating lipids in plasma using techniques such as mass spectrometry and liquid chromatography. And, through a fruitful collaboration with two local organizations — Midlife in the United States (MIDUS) and the Survey of the Health of Wisconsin — they have acquired human samples for testing.

Chris Coe, a professor emeritus in the UW Department of Psychology, oversaw the Biomarker Core for MIDUS before retiring in 2021. He approached Simcox because he had heard about her expertise in lipids and metabolism.

“We had generated lipid profiles for over 2,000 middle-aged and older Americans,” explains Coe. “Judi provided us with expert guidance on how best to analyze the hundreds of lipids that had been quantified. She has a deep knowledge about this growing field that has so much relevance for human health.”

In addition to helping the MIDUS team, Simcox and her lab tested samples for their own experiments. They were able to measure around 480 lipids in the human plasma samples, some of them known and some unknown — and most not considered biomarkers of disease. Further analysis of the lipids found that those associated with cardiovascular disease in Black populations were also relevant in the white population. These results are promising. It seems likely that more comprehensive biomarkers of cardiovascular health could be identified for a greater proportion of the general population.

The lipids that Simcox and her lab are identifying fall into various categories. Some are oxylipins, lipids with oxygen groups that are built from omega-3 and omega-6 fatty acids in the diet, that can act as signaling molecules. These lipids call for immune responses in the body — namely, increased white blood cell and macrophage counts and vein constriction.

But the main questions with these lipids are whether they serve as biomarkers for cardiovascular disease and, if so, what is their relationship with the disease? Because it’s difficult to control human behavior to alter lipid profiles, and because self-reports from study subjects can vary in quality, Simcox’s team is turning to mouse models to answer those questions. These studies give them the ability to control the parameters of diet and activity, study a mammal with anatomies and processes similar to humans, and construct a more detailed picture of the roles of lipids in the body.

“We want to know where these lipids are produced, how the production is regulated, how they get transported, where they’re going, and what they’re doing once they get there — just the basic questions of life,” says Simcox with a smile.

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Working to answer many of these questions about lipids is Jess Davidson, a graduate student in the Integrated Program in Biochemistry and a member of Simcox’s lab. She focuses on biomarkers for heart disease in people with type 1 diabetes. People with type 1 diabetes often have normal (rather than high) baseline levels of LDL and triglycerides, making those biomolecules poor markers of cardiovascular disease in that population. This is why Davidson is looking at individual lipids in the plasma, including those contained within LDL. It’s possible that one of those will be a better predictor of cardiovascular disease than LDL and triglycerides.

For this project, Davidson analyzes human blood samples from the Wisconsin Diabetes Registry Study. Participants enroll at the time of their initial diagnosis, and some have been with the study for more than 30 years.

“We have banked plasma samples for each person over the years and all of the clinical information that’s been collected,” says Davidson. “We bring them in for another appointment, and I’m able to interact with those patients, talk with them, and then go to the lab to ask really good scientific questions that can impact how their disease is monitored or treated.”

Davidson is a first-generation college student. She completed an undergraduate degree in biomedical engineering at Johns Hopkins University and worked as a research technician for several years. Davidson intended to go into a combined MD/Ph.D. program but realized that, while she enjoyed interacting with patients, treating them wasn’t her skill set. Her true passion, she discovered, is people-focused research.

When looking for a graduate program, Davidson was still considering how to marry her interest in bench science with her desire to help patients. When she talked to Simcox, she realized not only was this possible, but she could find a graduate mentor who would be supportive of her plans.

“Judi told me that there would be a way to do it. I’d have to seek it out, but there are ways I could collaborate around the hospital, talk with patients, and collect survey data,” Davidson says. “She’s helped me bring this aspect to my work and find opportunities that fit my interests.”

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It’s no surprise that Simcox invests so much in the students and scientists she works with given her own experience with mentors. Her first of many pivotal mentor relationships was with Gerald Shields, the professor she barraged with questions back in college. When he asked her to join his lab, she was concerned that doing research rather than waitressing would make it harder to pay her way through school. Shields told her about a fellowship that could help. But when they discovered the fellowship funding was no longer available, he and his wife donated the money to pay Simcox for her work. She later asked Shields why he did this, and he told her that when she became a professor, she’d know that some risks are always worth taking.

“He taught me about potential and the importance of mentorship,” says Simcox. “I think of him every time I take a new student into my lab.”

In graduate school in Utah, another mentor, medicine and biochemistry professor Donald McClain, taught Simcox to recognize and embody her values. “I learned with Don to live a value-driven life and always keep in mind what I wanted to share with the world as a scientist,” Simcox says. “I knew I wanted to be a community-based scientist and make the science around me better.”

Now, in her own lab, Simcox cultivates a community of researchers who work independently but collaborate easily. They also engage with members of the broader community around them, such as aspiring scientists and grade-schoolers interested in STEM fields.

“From the start of talking with Judi, I saw her focus was not just on science but also on reaching out to other populations, and it spoke to me,” Davidson says. “Outreach is a focal point of what we do in the lab. For example, we do outreach with a lot of high schools, and we give talks to the American Indian Science and Engineering Society.”

The lab also hosts a scholar as part of the Post-baccalaureate Research Education Program (PREP), an NIH-sponsored initiative that Simcox was instrumental in bringing to UW–Madison. Scholars are individuals from underrepresented groups who have earned bachelor’s degrees and are looking to learn about graduate programs in biomedical research fields. PREP completed its first academic year on the UW campus in 2022–23, and Simcox’s scholar during that time was Autumn Chevalier, an enrolled member of the Menominee Tribe.

Davidson sees the effort that Simcox puts into outreach and supporting diverse populations, and she aims to do the same in her own career. Hoping to become a professor herself, Davidson also wants to run a lab and provide mentorship to underrepresented students.

“Judi is an incredible resource for any student,” Davidson says. “She offers support and is willing to have hard conversations. She’s an advocate for anyone that needs it. I knew early on she was the kind of person and scientist I want to be.”

Simcox is always seeing opportunities to pay it forward. From her perspective, the doors that were opened early in her schooling should be accessible to everyone, not just those who can afford certain programs or those whose parents and grandparents went to college. The focus on creating opportunities led Simcox to serve as co-mentor for the American Indian Science and Engineering Society Chapter at UW–Madison, work at the national level with the Society for the Advancement of Chicanos and Native Americans in Sciences, and with the Native American Center for Health Professionals.

Diversity in science and health is fundamentally important to Simcox, and her work in these areas was recognized in May by the Howard Hughes Medical Institute when she was named a Freeman Hrabowski Scholar. The program supports early-career faculty who have shown outstanding commitment to diversity, equity, and inclusion in science.

“Science has to be driven by people in the community,” says Simcox. “There’s diversity in the community, so there should be diversity in labs. Diversity changes the types of questions people ask. If you have people from different backgrounds, they ask different questions and answer them in different ways.”

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Simcox’s passion for supporting diversity and equity merges with her research as she works to make sure that all populations have access to responsive and accurate health care. In addition to her work on lipid markers of cardiovascular disease, she is involved in a new Alzheimer’s disease study.

Carey Gleason leads the Inclusion of Under-Represented Groups Core at the Wisconsin Alzheimer’s Disease Research Center and is an associate professor in the UW Department of Medicine. She is also a clinical neuropsychologist who focuses on patients with memory disorders. In her efforts to invite Black and Indigenous groups to be part of the conversation about Alzheimer’s treatment and prevention, she wanted to find researchers who were members of those communities.

“We do better science when we do inclusive science,” Gleason says. “I wanted to partner with Judi to make sure that we brought into the science leadership someone who understands that cultural lens and also brings the highest caliber of scientific skill and creativity.”

Gleason and Simcox have just started their work together, but they’re already bringing Indigenous trainees into their labs who have an interest in the bench science and in being present in the community. Earlier this spring, they welcomed the first scientist to be co-mentored through their collaboration. Lauren McLester-Davis (who goes by her Oneida name, Yowelunh) will study characteristics and markers of Alzheimer’s disease in Native American populations.

Diabetes represents another overlap in Simcox and Gleason’s work. It’s one of the major risk factors for Alzheimer’s disease, and metabolic dysfunction is closely tied to early changes in Alzheimer’s patients.

“American Indian populations have a high prevalence of diabetes,” says Gleason. “And a recent study found that American Indians and African Americans are the two groups at highest risk for Alzheimer’s disease.”

Gleason hopes that a better understanding of these relationships and statistics can lead to increased quality of care for all Alzheimer’s patients. She also sees a role for the communities themselves — with Indigenous scientists as a vital piece of that puzzle.

“Collaborating with Indigenous scholars means there are people on the team who have a bridging perspective intrinsically connected to their science,” explains Gleason. “We want to work with these Indigenous scientists in ways that honor the different ways of knowing. It can’t just be the Western scientists imparting Western knowledge; instead, we want to demonstrate an intercultural sharing of knowledge. To do this, we need to acknowledge and let go of our hubris as Western scientists. Many Indigenous scientists bridge these worldviews every day. They can mentor us.”

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In Simcox’s view, the concept of two-way community engagement expands the Wisconsin Idea, the principle that the university should influence the lives of people beyond the classroom. She started her lab shortly before the pandemic hit, and those uncertain times broadened the meaning of the Wisconsin Idea in her mind. Not only were researchers sharing their findings and expertise beyond the walls of the university, but people in the community were reciprocating with questions, comments, and trust in the experts. For Simcox, it was another chance to connect.

“I get incredible emails from people in the community asking about their children with metabolic issues or for resources on treatments and vaccines,” says Simcox. “We think a lot about what we give to the community, sure, but since being here, I’ve really seen what the community gives back to us. We all help each other.”

Coe, the psychology professor emeritus from MIDUS, witnessed the Wisconsin Idea in action in his work with Simcox. He has nothing but the highest praise for the work she does, inside and outside the lab. “Judi fulfills the ideals of the university, and we are fortunate to have someone like her as a member of our faculty,” he says. “She truly lives up to what former [Chancellor David Ward] once described as the university’s mission: the creation and transmission of knowledge.”

That knowledge grows out of challenging questions that Simcox continues to ask: How can connections with communities lead to better health care for all? How can diversity improve the process of science and its outcomes? Years after that formative high school assignment, she now regularly asks many tough questions that don’t yet have answers. She knows it will take many people — and many years — to find some of them. And she knows that, with more diverse voices asking the questions, it becomes more likely the answers will serve everyone.

“Judi has always said how important it is for science and academia to have a structure that promotes support for underrepresented groups, such as Indigenous communities and first-generation students,” Davidson says. “She is very adamant about putting in place programs that will exist beyond our timeline so that these structures can continue for many years.”

As she continues to study, experiment, mentor, and inquire, Simcox is working to ensure that future generations, and those excluded in the past, will have the opportunity to ask questions, find answers, and make the lives of all communities better.

This article was posted in Basic Science, Economic and Community Development, Features, Health and Wellness, Summer 2023 and tagged Alzheimer's disease, Biochemistry, Carey Gleason, Chris Coe, diversity, Donald McClain, Down syndrome, Gerald Shields, Indigenous community, Jess Davidson, Judith Simcox, Lauren McLester-Davis, lipids, metabolism, Midlife in the United States, outreach, Post-baccalaureate Research Education Program, type 1 diabetes, Wisconsin Idea.