Program in Cellular and Molecular Medicine (PCMM)

Here at PCMM, Hao has done outstanding work in structural biology and mechanistic immunology that has fundamentally revised our understanding of the molecular mechanisms of innate immune signaling.

David Oxtoby, President of the American Academy of Arts and Sciences, noted of the 2021 class of newly elected members, “The past year has been replete with evidence of how things can get worse; this is an opportunity to illuminate the importance of art, ideas, knowledge, and leadership that can make a better world.”

Congratulations to Hao and Akiko for this wonderful achievement!

He was cited “for the discovery of gene amplification in mammalian cancer cells, discoveries that contributed to establishing oncogene amplification as a tumor progression mechanism, elucidating non-homologous end-joining, and revolutionizing the understanding of how genomic rearrangements form and how they contribute to cancer.” The chief executive officer of the AACR, Margaret Foti, PhD, MD (hc), added, “Dr. Alt is a pioneer in the fields of genetics and immunology whose landmark discoveries have had a defining impact on the study of cancer biology. We thank him for his immeasurable contributions to cancer research and are proud to honor his ongoing dedication to progress against cancer with this award.”

In addition to his groundbreaking work on cancer, recognized with this award, his pioneering research in immunology helped define the processes that generate the immense diversity of antibodies that can be produced to ward off infection.

The PCMM community extends its warmest congratulations to Fred for this well-deserved honor!

This honor follows her election to the National Academy of Sciences in April, so this has been an exceptional year indeed for Judy. It is a fitting tribute to how her life's work of outstanding discoveries in immunology and inflammation have influenced the fields of health and medicine. Judy's achievements bolster the entire PCMM community, and we look forward to her many more successes and contributions to come.

Please join us in extending our heartfelt congratulations to Judy!

Dornase alfa, also called DNase 1, is FDA-approved for patients with cystic fibrosis, to break up thick mucus secretions and prevent lung infections. The trial is supported by the Massachusetts Consortium on Pathogen Readiness, and the drug is being provided by Genentech, a member of the Roche Group, which is also providing supplementary financial support.

“We hope this drug, which is known to be safe, will help reduce the inflammation that contributes to worsening respiratory distress in COVID-19,” says Benjamin Raby, MD, MPH, chief of the Division of Pulmonary Medicine at Boston Children’s Hospital and principal investigator on the study.

The 18-month study will randomize patients to twice-daily nebulized dornase alfa or placebo (a saline solution) within 48 hours after intubation and placement on a ventilator. Treatments will be given via the ventilator tubing, twice a day for up to 28 days. Researchers will then monitor both groups for up to 28 days, or until patients are no longer receiving mechanical ventilation, whichever is sooner. Neither the researchers nor the patients (and families) will know which treatment is being given.

The main outcome of interest is the number of patients in each group who are alive and ventilator-free 28 days after treatment. Other measures will include airway resistance to breathing, lung compliance (the lungs’ ability to stretch and expand), blood oxygenation, and length of stay in the ICU and hospital.

Why dornase alfa for COVID-19 pneumonia?

Some patients with COVID-19 pneumonia produce large amounts of thick mucus that can make effective delivery of oxygen by mechanical ventilation more challenging. Dornase alfa is an effective mucolytic — able to soften mucus and promote its clearance from the airways. In addition, dornase alfa may be able to reduce lung inflammation promoted by neutrophil extracellular traps, or NETs. NETs are webs of DNA and toxic protein released by neutrophils, first responders in the immune system, in an excessive effort to entrap invading microbes. NETs are also known to produce dangerous blood clots such as those that form in COVID-19 patients, and are known, in general, to contribute to blood clots in the lung capillaries, inflammation, and lung injury.

Denisa Wagner, PhD, of the Program in Cellular and Molecular Medicine at Boston Children’s Hospital, who helped to initiate the new trial, has been studying NETs and their role in unwanted clot formation and fibrosis (thickening and scarring of tissue) for more than a decade.

“Preclinical studies by several groups, including ours at Boston Children’s Hospital, have found that DNase 1 improved outcome in lung injury models and thrombotic models mimicking events that occur frequently in COVID-19, such as deep vein thrombosis, stroke and microvascular thrombosis,” Wagner says. “This suggests to us that treatment with DNase could be beneficial in severe lung injury observed in COVID-19.”

Although this study is limited to the lung, it’s hypothesized that NETs contribute to coagulopathies seen with COVID-19 elsewhere in the body.

Other study principals include Rebecca Baron, MD, and Laura Fredenburgh, MD, of Brigham and Women’s Hospital and Meera Subramaniam, MD, and Gregory Sawicki, MD, of Boston Children’s Hospital.

Boston Children’s Hospital is ranked the #1 children’s hospital in the nation by U.S. News & World Report and is the primary pediatric teaching affiliate of Harvard Medical School. Home to the world’s largest research enterprise based at a pediatric medical center, its discoveries have benefited both children and adults since 1869. Today, 3,000 researchers and scientific staff, including 9 members of the National Academy of Sciences, 21 members of the National Academy of Medicine and 12 Howard Hughes Medical Investigators comprise Boston Children’s research community. Founded as a 20-bed hospital for children, Boston Children’s is now a 415-bed comprehensive center for pediatric and adolescent health care. For more, visit our Answers blog and follow us on social media @BostonChildrens, @BCH_Innovation, Facebook and YouTube.

NAS membership is one of the highest honors that a scientist can receive, recognizing distinguished and continuing achievements in original research across all disciplines, from mathematics to biomedical sciences to social sciences.

This distinguished honor is a tribute to Judy's lifetime of truly outstanding work in immunology and inflammation. Her ongoing science and her broad contributions continue to be amazing. Please join us in extending our heartfelt congratulations to Judy!

Selection as a Distinguished Fellow is one of the highest honors bestowed by AAI, presented to members who have been active 25 or more years and have made outstanding contributions to science, demonstrating such qualities as “excellence in research accomplishment in the field of immunology; exceptional leadership to the immunology community in academia, foundations, nonprofits, industry, or government at a national or international level; notable distinction as an educator.”

PCMM congratulates Fred, Hidde, and Richard on this achievement!

The award honors members who have supported the society, demonstrated scientific excellence, and expanded the field of biophysics. Hao was honored “for fundamentally revising how we view intracellular signaling and cellular organization, through discovering supramolecular ‘signalosomes’ formed by innate immune signaling proteins, mechanisms that govern cooperative assembly, and proximity-driven enzyme activation.” TJ was honored “for his contributions to single molecule biophysics approaches which have furthered our understanding of complex interacting biological systems.” All six newly elected Society Fellows were honored at Biophysical Society’s 64th Annual Meeting on February 17 at the San Diego Convention Center in California.

PCMM congratulates Hao and TJ for achieving this honor!

Her work has revealed the importance of filament formation of nucleic acid sensors in self vs. non-self discrimination and transmission of innate immune signaling, as well as the molecular mechanisms of RNA-receptor interactions. A picture has emerged from this work in which each receptor multimerization step in the RNA sensing signaling pathway provides a specificity checkpoint that insures correct initiation of the antiviral response, and the efficiency of RNA-receptor interactions fine tunes the balance between immunity and tolerance.

Sun was named a Massachusetts Life Sciences Center New Investigator in 2009 and a Pew Biomedical Scholar in 2010. In 2015, she received the prestigious Vilcek Prize for Creative Promise in Biomedical Science and was named a Burroughs Wellcome Investigator in the Pathogenesis of Infectious Disease. Earlier this year, she received an NIH Director’s Pioneer Award. Sun will be nominated to become the first incumbent of the endowed Oscar M. Schloss MD Professorship at Harvard Medical School, based in PCMM and the BCH Department of Pediatrics. There will be more news in the near future.

We are thrilled to have Sun Hur as a PCMM colleague!