Our Donors' Impact

Learn how donors are making a difference through fellowships for young researchers.

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A woman in a pink shirt talks to a group of people in a lab.

Whitehead Fellow Silvi Rouskin

Credit

Gretchen Ertl/Whitehead Institute

 

The importance of donors’ support is not theoretical: at Whitehead Institute, philanthropy is translated into discovery and, longer term, into better understanding of human health and new ways of diagnosing and treating disease. Here are two illustrations of how our donors are having a major impact by advancing the next generation of discovery.

Scott Cook and Signe Ostby

Scott Cook and Signe Ostby are passionately committed to creating opportunities through education, innovation, and medical research -- and their support of the Whitehead Fellows Program is a highly effective way to do just that. By creating the Scott Cook and Signe Ostby Fellowships, they are enabling two dynamic young researchers to pursue their unique and innovative scientific visions. The resources Cook and Ostby are providing are also helping Whitehead Institute to ensure that these talented women have the opportunity to pursue impactful careers, themselves, and to become powerful role models for female students considering a future in biomedical research.

Scott Cook and Signe Ostby Fellow Olivia Corradin studies genetic and epigenetic changes that contribute to human disease. Her lab focuses on genetic variations that occur outside of the protein coding region and how the resulting changes in gene expression relate to disease risk factors. The work looks in particular at multiple sclerosis (MS) and Opioid Use Disorders. Thanks to the resources made available through her fellowship, Corradin has developed a new approach to identify the cell types that are critically altered by genetic risk factors. That approach -- which Corradin outlined in a paper published in Cell in April 2020 -- enables researchers to ask whether genetic alterations that increase one’s risk for developing MS do so by affecting the function of blood cells like T and B cells or brain cell types like neurons. The Cell paper identified genetic factors that alter the function of oligodendrocytes, the cell type responsible for generating myelin, a protective layer for neurons in the brain. And it demonstrated how these genetic risk factors can alter the maturation of oligodendrocytes and generation of new healthy myelin. Corradin is now collaborating with a biotechnology company to understand MS disease severity and progression -- and to apply her study approach to other disorders.

Corradin’s lab has also made substantial progress in her study of Opioid Use Disorders, which seeks to identify epigenetic alterations that distinguish opioid dependent brains from healthy brains. This study has revealed new gene pathways critical to the pathology of opioid addiction; and it has found that genetic regions altered by opioid use often contribute to risk for neuropsychiatric disorders such as schizophrenia, depression, and bipolar disease. 

Scott Cook and Signe Ostby Fellow Kristin Knouse seeks to understand how tissues sense and respond to damage, working toward the long-term objective of developing novel approaches for regenerative medicine. Knouse’s studies focus on the mammalian liver, which has the unique ability to completely regenerate itself after injury. Her goal is to identify the molecular requirements for liver regeneration and ultimately confer that capacity to other organs. To that end, Knouse develops and employs novel genetic, molecular, and cellular tools that allow her research team to observe organ injury and repair in mice. This past year, the Knouse lab successfully developed and implemented genome-wide CRISPR-Cas9 screening in the mouse liver. This type of screening is an incredibly powerful tool for understanding the genes required for cellular behaviors, but until now its utility was restricted to cells in culture. Knouse and her colleagues brought this technology into the mouse liver and successfully screened for genes important for liver cells’ behavior. Through further studies using this tool, she hopes to identify genes required for the unique regenerative ability of hepatocytes -- genes that could be used to confer regenerative ability to other organs. Knouse is also working to extend this technology to other organs, such as the heart, to better understand why these organs cannot naturally regenerate.  

 

Paul and Andria Heafy

Paul and Andria Heafy have immersed themselves in Whitehead Institute science. They have come to know Whitehead Fellow Silvia Rouskin and have been so inspired by her groundbreaking research that they have provided the Institute with more than $2 million to support her as the Andria S. and Paul G. Heafy Fellow at Whitehead Institute, as well as to support her trailblazing research in HIV.

The Heafy’s support is enabling Rouskin to tease apart how RNAs fold in cells, how those structures can regulate their own expression in healthy cells, and how misfolded RNAs may be involved in neurodegeneration, cancer, and the human immunodeficiency virus (HIV). Although many aspects of HIV have been well researched, little is known about how the virus can make all of the proteins in the correct amounts necessary for productive infection from the same starting RNA molecule. Rouskin’s work indicates that the RNA itself may regulate which proteins are produced from it: the HIV RNA folds into several distinct shapes and by exposing or hiding certain signals on its surface, it can control which of its nine genes are expressed. HIV’s success at utilizing one RNA with multiple shapes to create distinct proteins may not be isolated. 

Indeed, Rouskin has found, a similar mechanism may affect gene expression in the human brain. Her lab has demonstrated in test tube studies that the sequence of a human gene called MAPT -- which is critical for normal brain function -- is capable of independently forming alternative RNA structures. They believe that those alternative RNA structures may affect the kind of protein that MAPT expresses, which could prove highly significant, because abnormal expression of MATP appears to lead to frontotemporal dementia and other neurodegenerative diseases. 

“It’s a pretty incredible place,” explains Andria Heafy. “For us, this is about seeing the next generation, which is one of the things Whitehead Institute does so well. They don’t just take people. They find the right people, and let them run. It’s just unbelievable to have that kind of environment that fosters such brilliance and unfettered imagination.”