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Mathers Foundation continues and strengthens its support of biomedical research

Examining the molecular processes of COVID-19 infections… exploring a potential new mediator of liver disease… both are important early-stage studies now underway at the University of Massachusetts Medical School because of two major research awards totaling nearly $1 million made by the G. Harold and Leila Y. Mathers Charitable Foundation in 2020.

Since its inception in 1982, the Mathers Foundation has awarded 12 grants totaling more than $4.5 million to six principal investigators in central Massachusetts, first at the Worcester Foundation for Biomedical Research (WFBR) and then to UMMS after the foundation merged with the medical school in 1997.

“This is a long and important relationship, and we are thankful for the support of the Mathers Foundation,” said Thoru Pederson, PhD, the Vitold Arnett Professor of Cell Biology, professor of biochemistry & molecular pharmacology and associate vice provost for research at UMMS. “It is quite impressive to see how the Mathers Foundation has risen, in a relatively short period of time, to become a national force funding early and innovative basic science research at many top institutions around the country.”

The first award made to UMMS in 2020 supports investigation into a potential new mediator of liver disease proposed by Jane Freedman, MD, the Edward Budnitz, MD, Professor in Cardiovascular Medicine and professor of medicine at UMMS, and director of translational research for the UMass Memorial Heart and Vascular Center, where she is an attending physician.

Dr. Freedman’s current research focuses primarily on the genetic and molecular mechanisms that cause the clots that lead to heart attacks and strokes. Much of that work focuses on platelets, which are small cell fragments that circulate in the bloodstream. In a basic study looking at the relationships between obesity, heart and liver disease, Freedman’s lab made a novel observation.

“We have preliminary human and basic data suggesting that platelets may also be related to health of the liver in the setting of non-alcoholic liver disease,” Freedman wrote in the grant application. “We propose to study the platelet in this setting using a variety of models to determine if the platelet can ‘heal’ liver abnormalities, and if there are specific targets that can be manipulated to better understand the complex relationship between the liver and the platelet as well as suggest potential future therapeutic targets to help alleviate the risk that being overweight or obese contributes to cardiovascular disease.”

The second 2020 award supports a COVID-19 project led by Robert Finberg, MD, the Richard M. Haidack Professor of Medicine, chair and professor of medicine; Anastasia Khvorova, PhD, the Remondi Family Chair in Biomedical Research, professor of RNA therapeutics; and Jonathan K. Watts, PhD, associate professor of biochemistry & molecular pharmacology. Both Drs. Khvorova and Watts work within the RNA Therapeutics Institute at UMMS.

The investigators are analyzing which airway cells are infected by SARS-CoV-2 (the virus that causes COVID-19). They are examining how specific genes, both in the virus and in the human cells, are involved in the infection and replication processes. They are also studying which genes in the host cells are involved in the immune response to the infection. That genetic information, along with data published by others, will be used by Khvorova and Watts to design novel RNA- and DNA-based molecules that can target the viral and host cell genes to treat or prevent COVID-19.

A generous history of support

The first Mathers Foundation research award made in central Massachusetts was in 1985 to Paul Zamecnik, MD, an investigator at the WFBR who, over the course of a long career at Massachusetts General Hospital, had made seminal discoveries in protein synthesis, including the discovery of transfer RNA, as well as inventing a novel approach to regulating genes, called antisense DNA. (Dr. Zamecnik passed away in 2009.)

“There is a historical thread running through the Mathers Foundation’s early support of Paul’s work, right to the present day,” Dr. Pederson said. “The COVID-19 project, for example, will use, in part, the technology of antisense DNA that Paul pioneered, and which has since evolved into a major field.”

In fact, Pederson was a witness to, and a participant in, that history. He was a scientist at the WFBR and worked with Zamecnik on a new version of antisense DNA. In 1985, Pederson was the president of the WFBR when first contact was made with the newly established Mathers Foundation.

“Paul and I always valued the courageous decision the Mathers Foundation took on antisense DNA, and on him,” Pederson wrote in a memoir of Zamecnik, published by the National Academy of Sciences in 2011.

Shortly after that first grant from the Mathers Foundation, Pederson was invited to speak with its board of directors and share ideas with the nascent organization about how to approach grant-making for basic scientific research.

“They have developed a motif of focusing on new ideas and early projects that have not yet captured the attention of the NIH,” Pederson said. “Their commitment to early research by talented investigators is a powerful model that allows scientists to follow their ideas, knowing that not all, but certainly some, will lead to important discoveries.”