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Physician-scientist review information in the lab with Ph.D. student Joanina Gicobi.

May 8, 2024

By Mayo Clinic College of Medicine and Science staff


As Joanina Gicobi, Ph.D., nears the end of her research education and graduates this May, she shares her research journey, lessons she learned along the way, and hopes for the future.

Hometown: Chuka, Kenya
Graduate track: Immunology
Research mentor: Haidong Dong, M.D., Ph.D., Mayo Clinic in Rochester, Minnesota

Before coming to Mayo Clinic, I had developed an interest in immunology, working as a technician at Dana-Farber Cancer Institute. When I began the Ph.D. program at Mayo Clinic Graduate School of Biomedical Sciences, I realized that I enjoyed problem-solving and was especially motivated by the idea of enhancing the functions of killer cells in the body for tumor clearance. The lab of Hidong Dong, M.D., Ph.D., professor of immunology at Mayo Clinic, was already working to address this question. He continues to inspire and amaze me with the questions he asks and the ways he addresses scientific problems.

For students considering a doctoral degree in biomedical sciences, I say — go for it! You can make discoveries at any stage of your career, including during your Ph.D. training.

Studying immune cells that fight cancer

The body contains naturally occurring immune cells known as CD8+ T cells that serve as a cancer surveillance system. The cells have the capacity to identify and kill off malignant cells. The problem is that CD8+ T cells become depleted of energy and, in their "tired" state, lose the ability to destroy the cancer. My thesis work asked whether it may be possible to enhance the energy of CD8+ T cells by increasing their internal energy source, known as mitochondrial ATP, while limiting the production of a toxic byproduct of metabolism that can further damage cells.

In my research, I used RNA sequencing and identified a key enzyme that plays a role in CD8+ T-cell metabolism. The enzyme is malic enzyme 1, or ME1I then used mRNA transfection technology, which inserts protein-producing messenger RNA into cells, aiming to increase the levels of ME1 in human CD8+ T cells. Our team found that we were able to increase the availability of mitochondrial ATP, providing additional energy to CD8+ T cells. We were also able to increase their killing capacity without the accumulation of toxic molecules, known as reactive oxygen species, that induce cellular exhaustion.

Importantly, we showed that ME1 increases the killing capacity of immune cells from patients with advanced cancers who have not responded to standard therapies. For patients with advanced disease and limited treatment options, ME1 may have a therapeutic use on its own or in a combination therapy. Our work has been accepted for publication in the journal Science Advances.

Commencement

Learn more about Commencement for Mayo Clinic Alix School of Medicine and Mayo Clinic Graduate School of Biomedical Sciences.