Published February 25, 2022
A trainee in the doctoral program in biochemistry has been awarded a two-year predoctoral fellowship from the American Heart Association for her research on a fatal neurodegenerative disorder.
Frances Smith will receive $64,000 in stipends, health insurance and project support for her work on Friedreich’s ataxia (FA), an in-born error in iron metabolism which manifests as a motor disorder in teenagers and young adults and progresses to cardiac dysfunction and death.
She graduated from the master’s degree program in microbiology and immunology at the Jacobs School of Medicine and Biomedical Sciences and earned a Bachelor of Science degree in biology from Clarkson University.
“I have a non-canonical origin story in the Department of Biochemistry. I started as a master’s student in the Department of Microbiology and Immunology because I had fallen in love with virological research as an undergraduate,” she says.
“In my second semester as a graduate student, I stepped out of my comfort zone to take one of Dr. Kosman’s biochemistry classes on protein structure and function,” Smith says.
“It was obvious that Dr. Kosman was extremely passionate in not only the findings of biochemistry, but also with the underlying mechanisms with which they were identified. This really resonated with me as my draw to virology was the mechanism by which viruses harbor host control.”
And while she is not currently working on a virus disease model in Kosman’s lab, she says she is “elated to be understanding mechanistic progression of other diseases.”
Smith says Kosman “fosters an environment that promotes scientific growth in all of his trainees, no matter the experience level.”
“He encourages the perfect balance of independence and support at all levels; be it scientific design, data interpretation, writing, and even with personal conflicts,” she says.
“One thing that I always appreciate is that Dr. Kosman will never discourage me from pursuing something, whether an experiment, a side project, or a resume-boosting opportunity.”
Upon seeing her first paper after encountering Smith as a master’s student, Kosman says he encouraged her to continue on in a doctoral program.
“I did not know her and was not familiar with her background. Whatever concerns I had about her preparation for the material we covered, the first paper she turned in dispelled them: it was knowledgeable, well-researched and well-written,” he says.
Kosman says Smith was not deterred when the COVID-19 pandemic struck shortly after she began her doctoral program training.
“She took upon herself the task of writing an extensive review that basically outlined the premise that she developed for her doctoral thesis,” he says. “Within a couple of months, she presented me with her manuscript, that with very few edits, was submitted to the journal Frontiers in Molecular Biosciences.”
“Molecular Defects in Friedreich’s Ataxia: Convergence of Oxidative Stress and Cytoskeletal Abnormalities,” was published in November 2020 — 11 months after Smith joined Kosman’s lab as a doctoral student.
Kosman says Smith has brought two new and significant techniques to the lab — use of viral infection to generate stable cell lines expressing shRNA species to knock down specific protein expression; and Agilent Seahorse metabolic analysis that is used in studies on the mitochondrial basis of neurodegeneration.
“With the training she has provided to the other lab members, all are making use of these approaches in their own research projects,” he says.
“The interactions between Dr. Kosman and Frances are a wonderful example of the types of mentor-trainee relationships we create here at the Jacobs School,” says Allison Brashear, MD, UB’s vice president for health sciences and dean of the Jacobs School.
“Our programs and mentors are prepared with the students’ scientific development in mind and each student is encouraged to carve out their own unique path of training.”
Smith says, “neuronal death in the processing centers of the brain contribute to poor motor function in FA patients and abnormal iron accumulation in this brain region may be either a cause or effect of poor neuronal health.”
“The brain is particularly susceptible to infection, inflammation and nutrient imbalance; and so, there is a system of blood vessels that surrounds and protects it, called the blood-brain barrier,” she says.
Smith adds that recent research in some other neurodegenerative disease models like Parkinson’s disease shows that the blood-brain barrier is leaky and leads to brain iron accumulation and neuronal death.
“My research focuses on understanding if this could also be true in FA; because the literature lacks understanding of the brain iron accumulation, and furthermore, the blood-brain barrier integrity has never before been investigated in FA,” she says.
Smith says her research aims to improve the quality of life of patients in the early stages of FA during neuronal decline by understanding if the brain iron accumulation is contributing to a poor inner-brain environment.
“Quality of life is extremely important in patients, as the most prioritized clinical benefit to therapeutics in FA are walking and balance,” she says. “I hope that my research of the brain environment around the neurons responsible for these functions can benefit the FA population.”
Kosman notes that Smith’s background contributes to some of her most important strengths as a trainee.
“Frances comes from a farming community in the Finger Lakes; she's as comfortable around chickens as she is in the tissue culture hood,” he says. “She’s simply a centered, well-rounded young person and thoughtful, emerging academically-based scientist.”