Chan School graduate studies links between disease and aging – Harvard Gazette
It is one of the a series of profiles featuring some of Harvard’s top graduates.
As a master’s student in biology at the Tata Basic Research Institute in Mumbai, India, Sneha Dutta came across research in one of her classes that fascinated her. Written by William Mair of the Harvard TH Chan School of Public Health, it demonstrated that regulating a metabolic pathway in the brain can change the way we age. For a whole host of illnesses, the biggest risk factor was simply getting older.
“There is a plethora of noncommunicable diseases such as cancer, diabetes and neurodegeneration that plague our society, where the main risk factor is old age,” says Dutta. “So you can really think of aging as some kind of disease.”
Of course, if aging is a disease, it means that there may also be a cure. “If you could target the underlying processes that go wrong with aging, you would be able to treat not just one, but multiple diseases at the same time,” she adds.
Intrigued by the idea, Dutta applied to Harvard Chan School and was accepted into Mair’s lab to study how cellular pathways go haywire as people get older. Dutta focused on the phenomenon of RNA splicing, the process by which cells capture fragments of RNA that ultimately code for functional proteins. As people get older, this process gets worse and worse and can lead to a myriad of health problems. But if researchers can find ways to keep the RNA splicing process orderly and optimized, Dutta argues that it might be possible to counter some of the damaging effects of old age and reduce the risk of disease. “By targeting these anti-aging pathways, the goal is not to make people live longer,” she explains. “The goal is for them to live healthier lives and improve their quality of life.”
Dutta first became interested in the biological basis of health at a young age. Growing up in Calcutta, India, she saw her father go into cardiac arrest when she was just 10 years old. “He was really young and had no other health complications, but suddenly one fine day he was on his way to work and had a heart attack. “
Doctors did bypass surgery and gave her a bunch of different drugs, but unfortunately the side effects of some of those drugs gave her diabetes. “They were doing their best to help her, but there are so many unknowns about these underlying networks in the body,” she says.
Determined to help those suffering from illnesses like her father, she studied microbiology at St. Xavier’s College in Kolkata before being accepted into the master’s program at the Tata Institute of Fundamental Research, a prestigious program with an emphasis on practical laboratory research. There, she studied malaria, a ubiquitous problem in India, looking for a protein that could be a candidate for a long-sought vaccine. It was one of the first times she understood how much laboratory science could influence public health and she was addicted to it. “I could clearly see how the research could have a direct impact on millions of people in countries where malaria is so prevalent and where finding preventive measures could be so helpful,” she says.
His current research at Harvard Chan focuses on the manipulation of RNA splicing pathways in C. elegans, a type of roundworm commonly used in laboratory research. The Mair lab studies dietary restrictions and has shown that reducing calorie intake without malnutrition in worms can make them live longer. What is not fully understood – and central to the lab – are the downstream effects that influence the benefits of dietary restriction.
Drawing on the research of Caroline Heintz, Principal Investigator, Caroline Heintz, Dutta showed that these longer-living worms need certain proteins in cells called splice factors. When worms are manipulated to remove these proteins early in their life, Dutta found, worms live shorter lives. “If you don’t have these splicing factors, then dietary restrictions and other longevity interventions won’t allow you to live longer,” she concludes. Removing them later, however, has no effect.
Understanding how these splicing factors work early in life could dictate how an individual ages or responds to aging interventions and treatments later in life. In addition, promoting the function of these splicing factors early in life could promote health and reduce the occurrence of age-related diseases.
Mair, associate professor of molecular metabolism, touts Dutta’s work and notes that it could help inform the development of new treatments in the future. “Sneha’s work shows how early-life RNA splicing factor activity in C. elegans determines subsequent responses to pro-longevity interventions,” explains Mair. “If this finding is true in humans, it will be essential in translating basic science into usable therapeutics, a first step towards precision medicine approaches for aging.”
As she prepares to graduate this summer with her PhD. from the Harvard Graduate School of Arts and Sciences, Dutta increasingly seeks to use his research skills to have a direct impact on patients around the world. She has previously accepted a life sciences consultant position at a Boston-based company to help biotech and pharmaceutical companies better strategize on how to market treatments. Ultimately, she hopes to be able to use the experience gained to overcome the logistical challenges that sometimes limit access to life-saving treatments in developing countries like India.
“I would like to be able to solve these problems and overcome the barriers that prevent companies from investing in developing countries so that everyone can hopefully benefit from these treatments,” she said.