Biology of Adversity Project launches at Broad Institute

Most people have experienced distressing events in their lives, such as violence, neglect, or natural disasters. These and other kinds of adverse experiences can have dramatic effects on physical and mental health, yet scientists don’t fully understand how they affect the body at the cellular and molecular level. To uncover how adverse experiences can inflict molecular “scars” in the genome and body and lead to negative health outcomes such as heart disease, researchers at the Broad Institute have launched an interdisciplinary, collaborative effort called the Biology of Adversity Project.

Initial funding for the project is provided by a $50 million gift from Treehouse Family Foundation, whose mission is to improve lifelong health and opportunity by preventing childhood adversity and reducing its effects. Jason Buenrostro, a core institute member at Broad, professor of stem cell and regenerative biology at Harvard University, and a 2023 MacArthur Fellow, leads the project. 

The effort convenes researchers from the Broad and other institutions, including institute member Karestan Koenen, who is also a professor at the Harvard T.H. Chan School of Public Health. Other project researchers are Ya-Chieh Hsu, Charles Nelson, and Bruce Ksander of Harvard University; Jakob Hartmann of McLean Hospital; Ravi Raju of Boston Children’s Hospital; Sara Prescott of The Picower Institute for Learning and Memory at MIT; Matthias Nahrendorf, Wolfram Poller, and Lauren Orefice of Massachusetts General Hospital; Francisco Quintana and Vadim Gladyshev of Brigham and Women’s Hospital, and Broad core institute member Fei Chen. 

A primary goal of the project is to learn how different forms of adversity, including acute traumatic experiences and more prolonged exposures, increase the risk of certain physical and mental health disorders, including cardiovascular disease, autoimmunity, and major depression. The project team will also create and share critical data and technology resources that will empower new research at any institution, all with the goal of finding ways to better diagnose susceptibility and treat adversity-associated diseases.

“It’s hard to overstate just how common adversity and traumatic experiences are and how profound their effects can be on child development and adult health,” said Buenrostro. “Adversity is a major driver of many health conditions, but we don’t really know how it gets encoded in genes or cells and then decoded in our bodies. This is precisely what we aim to find out in this initiative.” 

The Biology of Adversity Project is collaborating with and building on the foundation laid by the Broad Trauma Initiative (BTI), which was launched at Broad in 2022 with philanthropic support from Treehouse Family Foundation. Led by Koenen, an institute member at Broad and a professor of psychiatric epidemiology at Harvard T.H. Chan School of Public Health, BTI was founded to improve the health and well-being of trauma survivors. The initiative also closely collaborates with Archana Basu, an assistant professor at Massachusetts General Hospital and a research scientist at Harvard T.H. Chan School of Public Health, to implement trauma-informed care programs. 

“We know that most Americans will experience a traumatic event — a serious accident, disaster, or violence — at some point in their lives, and events such as natural disasters are becoming more common and impacting large populations,” Koenen said. “What happens when people experience trauma from these kinds of events? Why do some veterans come home with PTSD? These sorts of questions have been studied by clinical psychologists and epidemiologists but not as much by laboratory scientists.” 

Koenen added, “The Biology of Adversity Project is tackling these really important questions and new molecular insights from this work will point the way toward new and better interventions that will hopefully help people be more resilient in the face of adversity.”

“There’s no doubt that this will be a challenging project, but the negative impacts of adverse experiences on health are too important to ignore. If we can get to the molecular basis of how adversity affects the human body, it will be a huge advance,” said Todd Golub, director of the Broad Institute.

Genes, cells, and new tools

The new project is studying the biological effects of a range of adverse life experiences. To do this, Buenrostro and his colleagues are applying the latest advances in single-cell genomics to analyze cells and tissues from both large human cohorts and mouse models of stress. They hope to discover which genes, cells, and biochemical pathways are altered by exposure to adversity, and to identify the damaging genetic, epigenetic, and cellular “scars” that drive the unhealthy impacts of adversity.    

The project is integrating expertise from various disciplines to study the impact of adversity on the whole organism, beyond just the brain. For example, the team includes scientists who study the peripheral nervous system and how certain signals from the brain can disrupt cells and tissues throughout the body.

“We are confident that a deeper understanding of these mechanisms will one day lead to new kinds of diagnostics that can identify the trauma-exposed people who are more likely to develop adverse health outcomes so that patients can receive better clinical care earlier,” Buenrostro said. 

Buenrostro came to this project partly because of his innovations in epigenetics — the study of chemical changes to our DNA that alter gene expression. Studying these changes in both humans and animal models is an important part of this work, because adverse life experiences are encoded into our DNA by epigenetic changes that then have ripple effects in cells and tissues throughout the body. “Epigenetics connects our environment to our health,” Buenrostro said.

Over the last decade, Buenrostro and his lab have developed several widely used research tools for studying the epigenome at single-cell resolution. As part of the new project, they will develop new tools to accelerate scientific discovery that could lead to potential therapies and diagnostic markers. 

"Imagine a world where we understood how our daily stress was damaging our health. We could track stress with simple tests and intervene to prevent or reverse its harmful effects,” said Prescott, a project team member at MIT. “In this world, adversity would no longer silently fuel chronic diseases.”

Personal connection

Buenrostro feels a strong personal connection to the new project. He was the first in his family to attend college, and he says many people close to him experienced abuse, addiction, and were the victims of crime. He noticed that while some people showed resilience in the face of these challenges, others did not. 

“As scientists, there are some things that we study because of the learning opportunity and other things we study because we’re passionate about trying to solve an important health problem,” Buenrostro said. “For this project, I think both things are true. I have a deep personal connection with this research mission.”

Looking ahead, Buenrostro says he wants to grow the Biology of Adversity Project community and emphasizes the need to collaborate with people from a variety of disciplines. Together with his collaborators, he aims to build a team that includes researchers from public health, social sciences, molecular and cell biology, neurobiology, and technology development.  

As the project grows, Buenrostro envisions studying adversity in a broader way.

“We want to leave the door open to think about more and different types of adversity and how people across the U.S. are affected,” Buenrostro said. “So we envision a future where we're studying this in a holistic way to include many of the key factors that impact communities.”