You could say doing research to solve an intractable challenge in human medicine is in Sanha Kim’s DNA.
Kim recently received a National Science Foundation Graduate Research Fellowship Program award to fund his next three years as a Ph.D. student and research assistant in chemical engineering professor Roseanne Ford’s lab at the University of Virginia School of Engineering and Applied Science. With the fellowship, one of the nation’s most prestigious funding programs for graduate students, he will study a remarkably adaptive, and thus dangerous, infection-causing bacteria, Pseudomonas aeruginosa.
The path that led Kim to UVA was inspired by his mother, Young Ju, an associate professor at Virginia Tech who researches and promotes holistic health practices to combat chronic illnesses such as diabetes. Growing up with her example of service, his goals crystallized early.
“By the time I finished high school, I knew my dream was to transform my education into a career where I could advance knowledge boundaries and help develop solutions to persistent problems,” Kim said.
Even when Pseudomonas aeruginosa doesn’t kill, patients often endure repeated treatments with antibiotics, and the bacteria’s presence is particularly threatening for cystic fibrosis patients.
The bacteria thrive in mucus, a normally beneficial substance our bodies produce in abundance – maybe as much as 1.5 liters a day. Mucus protects us from illness by coating our sinuses, lungs, throat, intestines and stomach. In cystic fibrosis patients, a genetic malfunction leads to thick, sticky mucus in the lungs, which makes breathing difficult, is tough to expel and increases risk for infection.
Kim’s research objective is to generate a computational model that can predict how Pseudomonas aeruginosa grow and move in the physical confinement of the mucus and with evolving nutrient conditions.
“These are critical questions in the case of P. aeruginosa and cystic fibrosis because these bacteria have developed an impressive range of adaptations that help them survive treatment and sustain their presence in lung mucus,” Kim said. “How they do this appears to be a combination of external factors and even specialized cell-to-cell communications, but specifics regarding these pathways are still obscure.”
Kim’s end goal is to expand capacity to understand how pathogens respond to highly complex diseased environments, giving researchers and clinicians better tools that will help them design more effective treatments.
Ford’s area of expertise is bacterial chemotaxis, which is the movement of a population of cells toward or away from a chemical stimulus, or food source. Two years ago she joined a multi-institution team, led by UVA Engineering biomedical engineering professor Jason Papin, on a project to build multi-scale models of Pseudomonas aeruginosa interactions with mucus in fibrotic lungs.
“Multi-scale is connecting what’s happening at different levels,” Ford said. “Jason’s expertise is in understanding the chemical reactions or metabolic processes going on inside one cell, and the external factors that regulate those processes, such as available foods, if oxygen is present, if there’s some toxin around that can affect the cell. His model accounts for what’s happening inside that cell.”
But researchers are left to assume all cells are the same internally, and each is experiencing different environmental conditions depending on location.
“You can’t keep track of every individual cell. At some point you have to say the average behavior of this population can be characterized by this population-level model,” Ford said, and that’s where Kim comes in.
“We can get a pretty good predictive outcome of, on average, the population has this response or shows this behavior,” Ford said. “By applying multi-scale modeling, we can probe the genomic-level changes in microorganisms that result from interactions with mucus and ultimately lead to infection, especially in cystic fibrosis patients.”
Kim joined the team when he arrived at UVA in 2020 as a Kirwan fellow. With the NSF funding, he is developing a multi-scale model using his own lab data from cultures grown in media engineered to mechanically mimic fibrotic lung mucus.
He is focused on the mechanical properties to study how far and fast the bacteria multiply and move in the material as a population. The team is also incorporating Papin’s “metabolic reconstructions” of individual cell processes to tie in the cell-level predictions, with the goal of allowing medical researchers to develop effective new treatments.
Eventually, Kim also will try to predict byproducts the bacteria will produce based on what is available for them to eat, including compounds called virulence factors.
“Virulence factors are produced by bacteria in high concentrations, and can modify how bacteria acquire nutrients, how cytotoxic they are to the environment and how they protect themselves against drug treatments,” Kim said.
As a chemical and biomolecular engineering major and food science minor at the University of Illinois Urbana-Champaign, Kim worked in two labs, one in the Department of Food Science and Nutrition – studying the inhibitory effects of certain food compounds on colon cancer – and the other in his home department, where he developed an interest in engineering biomaterials.
These experiences intersecting chemical engineering and human health reinforced early lessons from observing his mother’s work – that solutions to tough problems are usually multi-faceted, interdependent and may come from places you don’t expect.
“I saw how core engineering skillsets can design platforms that help to examine complex disease mechanisms,” Kim said. “Going back to my mom, it reminds me that some challenges are so complex that we need a lot of perspectives looking into it.”
"Sanha holds himself to very high standards and has an incredible work ethic. He likes to think about how things fit in the big picture of what he’s doing."
Roseanne Ford, professor of chemical engineering
Ford appreciated Kim’s willingness to make computational modeling – a research area he had not previously explored – central to his research at UVA, as well as his thoughtful approach to every challenge.
“Sanha holds himself to very high standards and has an incredible work ethic,” she said. “He likes to think about how things fit in the big picture of what he’s doing.”
That fits with Kim’s desire to use his education to serve others. It’s a calling he highlighted in his NSF fellowship application, writing he feels obligated to promote accessible higher education to anyone who’s motivated, regardless of circumstance. At Illinois, he co-founded and helped run a Books to Prisoners chapter at the university.
Kim is one of eight UVA Engineering graduate students and two graduating fourth-years this year to receive NSF fellowship awards, which recognize the recipients’ potential contributions to science, technology and education, as well as society and future needs of the nation. The awards are more about the person than the research projects proposed in their applications.
Each includes a yearly $34,000 stipend for three years plus $12,000 for tuition to the institution, allowing recipients to complete their education without worrying about finding additional funding.
“I’m incredibly excited for Sanha,” she said. “I’ve had several highly qualified, outstanding students I would’ve expected to receive the fellowship who did not. I’ve tempered expectations knowing how competitive it is, so this was just such a pleasant surprise for me to see Sanha’s hard work rewarded in this way.”