PhD Candidate Katy Kesler has received a predoctoral fellowship from the United States Department of Agriculture’s National Institute of Food and Agriculture (USDA NIFA). The Education and Workforce Development Program from USDA NIFA’s Agriculture and Food Resource Initiative (AFRI) funds Kesler for 3 years with $180K to support her stipend, travel, professional development, and research.

Importantly, this AFRI funding will support Kesler in expanding the research skills and technical competencies needed to initiate her own independent research program upon graduation.

“Katy stands out among her peers for her incredible drive and dedication, independence, and strong work ethic,” says Dr. Ángel Abuelo, Kesler’s advisor and associate professor of cattle health at the Michigan State College of Veterinary Medicine. “Although this project fits within the context of my existing research programs in the area of calf health and oxidative stress, the studies proposed by Katy are unique to our laboratory and represent her independent scholarly efforts. Achieving an AFRI predoctoral fellowship is a great accomplishment that recognizes Katy’s skills.”

Respiratory disease is the second leading cause of death in pre-weaned calves. Boosting the efficacy of early-life respiratory vaccines is expected to have a major impact on calf health, further reduce antimicrobial treatments, and improve farm profitability. Thus, Abuelo believes that this research could lead to important changes in how producers manage neonatal calves to promote optimum immune function and disease resistance.

Kesler’s project, “Harnessing the antioxidant potential of zinc and metallothionein to improve neonatal dairy calf vaccine responsiveness,” seeks to help dairy calves respond more effectively to vaccines. According to Kesler, roughly a third of pre-weaned calves in the US dairy industry become sick, while approximately 5 percent die. Vaccines are essential tools for dairy producers to support the health of their calves and sustainability of the industry; however, vaccines are less effective in pre-weaned calves than they are in older cows. This is partially due to the oxidative stress that the pre-weaned calves experience, which compromises their immune systems.

“Redox balance, or redox biology, is the relationship between pro-oxidants and antioxidants in the body. While it’s not necessarily a one-to-one ratio, both have functions, and too much of either is bad, so it’s about a safe range. When we get outside the range on either side is when we see oxidative stress, which is the cell damage that happens as a result of these pro-oxidants,” says Kesler.

Vitamins and minerals are micronutrients, which play an important role in managing and reducing oxidative stress. Zinc is an essential micronutrient; metallothionein is a protein that chaperones zinc. Together, they could support calves’ immune cell function and oxidative status.

However, zinc’s role and supplementation guidelines have yet to be identified for dairy calves. This is Kesler’s goal—to uncover the effect of zinc supplementation, mediated by metallothionein, on a neonatal calf’s lymphocyte, or white blood cell, functions. These functions are a critical part of a calf’s immune system that directly relate to vaccine responsiveness; when functioning correctly, lymphocytes help protect calves from pathogens.

“Finding out that dairy calves naturally experience oxidative stress during a critical window for disease was eye opening,” explains Kesler. “My goal is to use zinc and metallothionein to target oxidative stress by optimizing the delicate balance between pro-oxidants and antioxidants in the body, known as redox balance.

“Zinc has a redox role with metallothionein, and outside of mitigating the redox balance, zinc has been associated with all these immunomodulatory properties. Being able to bring them together, I think, is what makes it unique.”

Kesler’s funding includes an international research experience—she’s targeting London for summer 2024. “At King’s College, I will learn from a metallothionein expert about working with metalloproteins and about the important role that zinc localization plays in the body during inflammation and disease.”

Being funded by AFRI feels, “Surreal,” Kesler says. “When I think about the other students I know who have been funded, they’re incredible—of course they got funded. It feels weird to be in that same category.”

As a student, Kesler is very familiar with the College of Veterinary Medicine. She earned her DVM in 2021, as well as her MS through the College’s Comparative Medicine and Integrative Biology Program, when she studied reproduction and microRNAs. Kesler is now a second-year PhD student. Based on the current trajectory of her research, she plans to graduate in 2025.

“Metallothionein is so hard to quantify,” Kesler explains. “It is a teeny, tiny protein with a unique composition, for which there are no bovine-specific immunoreagents. Not that many people look at the intersection of immunology and redox biology in dairy calves, which is one of the cool things about Dr. Abuelo’s research. He’s targeting how to solve this challenge we see in vaccines.”

Kesler has been at the College for six years, but there’s potential for that number to increase. “It has always been my dream to be a professor at a vet school. The idea of combining clinical medicine with research that has the potential to impact animal health, and being able to share the knowledge you have with others through teaching. Having a triple-threat position like that has been a dream of mine for a long time.”