As a girl growing up in Bulgaria, Elitsa Ananieva, Ph.D., wondered why some people died of diseases such as cancer and why so little was known about how to prevent or treat them.
“I promised myself that one day I will study cancer and try to find ways to help cure it,” she says. “This, combined with my fascination about the immune system, led me to what I do today – try to modulate the immune system to help better fight cancer growth.”
Associate professor of biochemistry and nutrition, Ananieva recently received a three-year $443,548 grant from the National Cancer Institute (NCI), National Institutes of Health, to advance her investigations with a project titled, “Elucidating the role of the branched-chain aminotransferases (BCATc and BCATm) as novel metabolic checkpoints of anti-lymphoma T cell immunity.” The grant will build on her lab’s previous studies that indicated two metabolic enzymes, the mitochondrial BCATm and the cystolic BCATc, slow down or suppress T cells – a type of white blood cell that’s part of the immune system –
in fighting cancer, including lymphoma.
While the two enzymes negatively regulate T cell function, they are critical for metabolizing branched-chain amino acids (BCAAs), part of proteins that are essential to human health. Our bodies can’t make BCAAs, so we obtain them from dietary sources – but if they’re allowed to build up in the blood, they can cause organ damage. The NCI grant will allow Ananieva to comprehensively characterize the role of BCAA metabolism in T cell immunity against lymphoma and learn more about the role of BCATc and BCATm in this process. BCATc is especially of interest, because cancer studies commonly agree the enzyme is highly produced in cancer cells.
“BCATc is appealing as a target for therapeutic interventions, because the gene that produces it is silenced in most of the organs of a human adult, except for the brain, but it’s overly produced in cancer cells. Any gene that is not produced in vital organs but is in cancer cells is considered a good target for cancer treatment, because there will be fewer side effects if a new drug is designed to suppress this gene or its product, the protein,” she says.
She plans to test whether targeting BCATc and BCATm would be beneficial to the “durability and functional integrity of the T cells during lymphoma eradication,” she says.
“The long-term goal of the grant is to provide new means to improve the T cell-mediated immune response and to address the current challenges with T cell-driven anti-lymphoma immunotherapy,” she adds.
Ananieva’s NCI funding is an NIH R15 grant, which requires that students be actively involved. That fits one of her research passions as well as DMU’s mission of educating students.
“This is the right environment to truly engage students in research, including opportunities to present and publish their work,” she says. “We set the experiments in a way that they provide medical and graduate students the opportunity to connect their classroom knowledge about cancer and immunity with the research tasks. We hope to deepen their level of competency, leading to a better understanding of pre-clinical studies and their importance for the discovery of new diagnostic options for the prevention of cancer or the reduction of the burden of cancer.”
Wayne Wilson, Ph.D., chair of biochemistry and nutrition, says it’s clear that his colleague “loves her job.”
“What I admire most is that she approaches every task, be it teaching, service to the University or her own program of scholarship, with tremendous energy and a positive attitude,” he says. “She obviously takes delight in being a faculty member at DMU, and her enthusiasm for her job is quite contagious.”
A highly motivated mentor
Since she joined the DMU faculty in August 2014, Ananieva has supervised one to four students in her lab at a given time, including those in the University’s Mentored Student Research Program. She also has engaged students in Waukee, IA, High School’s Aspiring Professional Experience program, or Waukee APEX. A past recipient of the APEX Catalyst Award, she has collaborated with students on projects ranging from crunching data on bone cancer to investigating the anti-cancer properties of dandelion root extract.
“Even during the pandemic, she had our students tap the R2 web-based database for cancer gene data from researchers from around the world,” says Holly Showalter, Ph.D., an APEX instructor. “As a scientist, she’s brilliant and passionate not only about her research but also about the students she works with. She’s like a superhero and is truly a catalyst for science education in high school.”
Ananieva has been a co-author with several students who have won awards for poster and oral presentations at the annual DMU Research Symposium. Michelle Brenner, D.O.’19, earned the Most Outstanding Graduate Poster in biomedical sciences at the 2016 symposium for her research on cancer cells and the leucine metabolism pathway, and she was one of four students selected that year to present their work orally. Now a third-year pediatrics resident at the University of Wisconsin-Madison, she knew even before medical school that she wanted to “connect the bench to bedside through research innovations” to enhance patient care.
“Dr. A does a great job explaining complex scientific concepts in multiple ways, and she develops well-thought-out scientific experimental plans to answer questions. I also learned from her how to best communicate complex research,” Brenner says. “This is an invaluable skill not only for researchers but also for physicians who need to be able to distill complex medical concepts into easy-to-understand ideas for patients and families.”
Ananieva acknowledges that recruiting students to one’s lab and the inevitable turnover can be “exhausting” for faculty; she has created Zoom training modules on basic lab techniques, data analysis and graphing so students can get up to speed more quickly. But engaging them in one’s lab is a win-win for both faculty and students, she says.
“Offering research opportunities to students is a way to actively engage them in the scientific process of discovery and greatly complements their work. They learn not only research techniques but also how to lead independent projects and work in a team environment,” she says. “Faculty also benefit, in it’s a way to recruit students who can work with them for an entire calendar year. Students bring good ideas. Overall, it strengthens the reputation of DMU as an institution that engages both students and faculty in high-quality research.”
Ananieva looks forward to opportunities to collaborate with clinical oncologists and translate the findings of her research directly to cancer patient care. She knows that would be no small feat.
“Cancer is not a single disease but a series of diseases. Even when different people suffer from the same type of cancer, they develop a different course of the disease and thus need different treatment approaches. This is because we all are unique in how our immune systems function and how we communicate with the environment,” she says. “Despite that, contemporary medicine is probably one step closer to offering better options to cancer patients relative to what they had 10 to 20 years ago.”
