Dr. Krystle Karaft, 24 years, studies the liver’s response to insulin and uncovers potential mechanisms involved in obesity and diabetes.
May 9, 2024 – Krystle Karaft has always been passionate about fitness. She takes indoor cycling classes, does strength training and yoga, and takes her dog for long walks in the park.
But her interest in health goes beyond exercise. She has also focused much of her career on nutrition. She has studied molecular biology as a volunteer with the U.S. military providing nutrition education to local communities, as a public health approach, and as a graduate student conducting laboratory research on how cells sense and respond to nutrients. I have approached this topic from both approaches.
Ms. Karaft received her PhD from the Griffin School of Arts and Sciences (GSAS) at Harvard University and studied in the Biological Sciences Program in Public Health at the Harvard T.H. Chan School of Public Health.
“I always saw my role as being on the more analytical side of things and thought my strengths were well-suited to research in a laboratory. However, my broader career goals are “It’s about bridging the gap between basic science and public health,” Karaft said.
She said she loves molecular science research, which requires a lot of imagination.
“I learn by visualizing concepts in my head, which is essentially what is needed to generate hypotheses at the molecular or cellular level,” Kalawt said. “Through experimental techniques used to detect cellular protein interactions and functions, my research unravels the complex molecular networks that facilitate communication between cells and tissues throughout the body.” It’s great to be able to glimpse the intricate details that underpin biological life in both.”
Basic science from a public health perspective
After earning her bachelor’s degree in molecular biology from the University of Pittsburgh, Karaft wanted to apply her basic science knowledge to improving health, so she joined AmeriCorps for a year. She worked in rural southern Ohio, providing nutrition education and outreach to children and adults.
“That was my first experience immersing myself in public health,” she said. “It was really great to have a perspective on how to build trust and apply evidence-based practices within the community.”
Her research focuses on promoting access to fresh, healthy foods and physical activity, which helps to reduce the impact of socio-economic factors such as food insecurity and income on nutrition-related diseases such as obesity and type 2 diabetes. This led me to think more about how it affects the risk of chronic disease.
“My experience with AmeriCorps further piqued my interest in the onset and progression of these diseases, and made me want to look deeper,” said Karaft.
To that end, Calaft returned to basic science. She took up her post-baccalaureate research fellowship in the National Institute on Aging’s lab, studying how diet influences the aging process. When considering the next step in her research career, she searched for a graduate program focused on basic science and public health, which led her to the Harvard Chan School.
Observe liver processes
Karafuto works in the lab of Brendan Manning, professor of molecular metabolism and acting dean of the Department of Molecular Metabolism. The lab focuses on a protein complex called mTORC1, which regulates cell growth and metabolism in response to signals conveying the availability of nutrients inside and outside the cell. Dysregulation of mTORC1 signaling can lead to a wide range of diseases, including obesity, diabetes, and cancer.
Specifically, Kalafut is interested in how mTORC1 is regulated in the liver. This organ helps keep the level of glucose, the body’s main energy source, stable and constant. The hormone insulin plays a role in this function, sending signals to the liver about whether glucose needs to be stored or released. Using a mouse model, Kalafut was able to isolate the signaling interaction between mTORC1 and insulin.
“Much of what we know about mTORC1 regulation and function has been defined using cell culture models,” she said. “However, it is not clear what is involved in the physiological environment, including the key signals that regulate mTORC1 and its function in different tissues. Therefore, using our mouse model, we is one way you can begin to understand.”
Dr. Karaft’s research confirmed that the mechanism by which insulin activates mTORC1, previously identified in cell culture models, actually occurs in mice. But she also discovered something unexpected.
“We found that in the liver, activation of mTORC1 is triggered by food intake alone, and that the previously observed mode of insulin regulation is not required for this process to occur. Preliminary data suggest that food intake alone does not require the previously observed mode of insulin regulation. “This suggests that amino acids can circumvent insulin signaling and activate mTORC1,” she said. “So far, this appears to be specific to the liver. In other tissues, such as muscle, both insulin and nutrient signals are required to fully activate mTORC1 signaling.”
Kalafut also identified a new role in the mTORC1 signaling pathway. This is a protein that may be involved in insulin resistance, a health problem that can lead to diabetes. She said if the details of the mTORC1 signaling pathway she discovered in mouse liver also occur in human liver, that information could be used to develop future treatments.
“Krystle came to my lab with a deep interest in how dietary intake alters whole-body metabolism and metabolic health,” Manning said. “She was one of the first people in my lab to take on the important challenge of understanding the regulation and function of mTORC1 in mammalian organs, focusing on the liver, the center of the metabolic response to food intake. Her development as a scientist while in my lab and studying this complex signaling network in animals to define the physiological effects of diet on metabolic transitions between fasted and fed states. I’ve been very impressed with her fearless nature. It’s a remarkable and innovative body of work.”
Developing new treatments and ensuring accessibility
After graduation, Ms. Karaft hopes to further expand her scientific expertise by working in academia, biotechnology, or pharmaceutical fields. “The mTORC1 signaling pathway is involved in a huge number of different diseases, including cancer, metabolic diseases, and aging,” she said. “I’m really excited to be able to apply my knowledge to the development of new treatments.”
She also hopes her research will have an impact beyond the lab. During her time at Harvard, Ms. Karaft has explored her interest in science policy. She participated in career discussions held by the Harvard GSAS Science Policy Group and met with science policy experts who work at organizations such as the Union of Concerned Scientists. She is also co-author of a paper published in the MIT Science Policy Review on the public health challenges posed by the world’s growing aging population, and its potential to accelerate the development of treatments for age-related diseases. focuses on certain policies.
“Scientists are motivated to discover and develop these new treatments, and they are the ones actually doing the hard work to do so. When it comes to price and availability, it’s a completely different business,” she said. “We want to be involved in some way so that our research efforts actually lead to improved health outcomes.”
– Jay Lau
Photo: Tom Kelleher
