Program in Cellular and Molecular Medicine (PCMM)

The Program in Cellular and Molecular Medicine (PCMM), is a research program at Boston Children's Hospital (BCH) recognized worldwide for its discoveries that increase the body's ability to fight disease and to heal. The breakthroughs of PCMM scientists are greatly increasing our understanding of the influence of immune defense and inflammation on medical discovery, healthcare, and disease management. PCMM officially joined seven other interdisciplinary programs at Boston Children's Hospital in October 2012 with the goal of increasing collaborations and scientific synergies. Our investigators are academically affiliated with Harvard Medical School.

We pursue six (at least) primary areas of research:

  • Adhesion molecules and inflammation
  • Autoimmunity and allergy
  • Genetics of immunodeficiency and cancer
  • Immune defenses against infectious diseases, viruses, and tumors
  • Stem Cells
  • Structural Biology

Featured News Stories

Researchers in the laboratory of Frederick Alt of the Howard Hughes Medical Institute and Program in Cellular and Molecular Medicine (PCMM) at Children's Hospital Boston made another groundbreaking discovery at the nexus of chromatin biology and immunology. Their work, published today in Nature (Dai et al., “Loop extrusion mediates physiological Igh locus contraction for RAG scanning”), showed that physiological deregulation of the WAPL chromatin-maintenance factor allows developing B lymphocytes to scan linearly through very long chromosomal loops to find and join gene segments that form diverse antibody repertoires. For more, please see the full article here.
Ba-et-al diagram
New studies from the Alt Lab, published in an article in the October 8 issue of Nature (Ba et al., “CTCF orchestrates long-range cohesin-driven V(D)J recombinational scanning”), have provided a major advance with respect to our knowledge of how diverse antibodies are generated during the development of progenitor B lymphocytes. For more, please see “Chromatin regulation enables generation of diverse antibodies” on Discoveries by Alice McCarthy.
A team out of the MIT, the Janelia Research Campus of the HHMI, Harvard Medical School HMS and Boston Children’s Hospital, describes a technique capable of imaging whole brains at exquisitely high resolution
Scientists from Boston Children’s Hospital and UC San Francisco describe a new way to create customized mouse models for studying the brain.
Studying blood samples from patients treated for malaria at a clinical field station in Brazil’s Amazon jungle, a team of Brazilian and American researchers has made a surprising discovery that could open the door to a new vaccine.
Researchers at Boston Children’s Hospital have reported a new cloning technique that has yielded the highest efficiency ever reported in mouse cloning, capable of producing 13 to 16 times more mouse pups than previous methods.
A new discovery about the spatial orientation and physical interactions of our genes provides a promising step forward in our ability to design custom antibodies. This, in turn, could revolutionize the fields of vaccine development and infection control.
antibodies in the gut
Lining the gastrointestinal tract, Peyer's patches (in green) contain germinal centers that create antibodies thought to have a role in maintaining a healthy balance in the gut.

Getting a grip on genetic loops

Announcements

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Tim Springer wins the Biophysical Society’s Founders Award

We are very pleased to announce that Tim Springer has been named the 2022 winner of the Founders Award by the Biophysical Society! The Founders Award is given annually for outstanding achievement in any area of biophysics.

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To quote his award citation, Tim was lauded “for pioneering contributions to biophysical studies of immune cell rolling, activation, and adhesion and for revealing the force-based activation of integrins through an innovative combination of structural biology, single-molecule mechanical measurements, and thermodynamic analysis.” He will be honored at the 66th Biophysical Society Annual Meeting in San Francisco this coming February. The PCMM community offers its warmest congratulations to Tim!

 

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Sun Hur named 2021 HHMI Investigator

We are delighted to announce that Sun Hur has been named a Howard Hughes Medical Institute Investigator!

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To quote her HHMI citation, her focus is “solving the immune system’s most perplexing mysteries.” Her work has contributed fundamental new insights into the mechanisms by which the immune system responds to viral versus host RNA, in turn providing major implications for therapy of viral infections, inflammatory diseases, and cancers. Sun’s accomplishment not only highlights her own outstanding research achievements, but also elevates the profile of our program as a whole. The PCMM community sends her its warmest congratulations!

 

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Denisa Wagner wins the American Society of Hematology’s Henry M. Stratton Medal

It with great pleasure that we announce that Denisa Wagner has been awarded the American Society of Hematology’s Henry M. Stratton Medal!

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As described by ASH: “The Henry M. Stratton Medal is named after the late Henry Maurice Stratton, co-founder of Grune and Stratton, the medical publishing house that first published ASH’s journal Blood. The prize honors two senior investigators whose contributions to hematology both basic and clinical/translational research are well recognized and have taken place over a period of several years.”

As the 2021 basic science awardee of the Henry M. Stratton Medal, Denisa was cited “for her contributions to the fields of vascular biology, inflammation, and thrombosis. Her discovery that von Willebrand factor (VWF) is contained in a reservoir within endothelial cells ready to coat the inside of blood vessels to aid platelet and leukocyte recruitment, was important to the understanding of vascular response to injury. The regulated release of VWF guided subsequent studies on the molecular basis of von Willebrand disease. Her recent study of neutrophil extracellular traps (NETs), chromatin actively ejected from neutrophils, has led to the discovery of a link between neutrophil activation and thrombosis. This link revealed a significant pathological contribution of ‘immuno-thrombosis’ to ischemic organ injury and cancer.”

Congratulations to Denisa for this well-deserved honor!

 

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Hao Wu and Akiko Iwasaki elected to American Academy of Arts and Sciences

We are delighted to announce that Hao Wu, Associate Director of PCMM, and Akiko Iwasaki of the Yale School of Medicine, PCMM Scientific Advisory Board member, have been elected to the American Academy of Arts & Sciences!

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Frederick Alt, PhD

PCMM Director Fred Alt receives 2021 AACR Award for Lifetime Achievement in Cancer Research

The American Association for Cancer Research (AACR) has honored Fred Alt, Director of PCMM, with the 18th AACR Award for Lifetime Achievement in Cancer Research. The award, established in 2004, is presented to individuals who have made fundamental contributions to cancer research through a single discovery or a body of work.

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Judy Lieberman elected to National Academy of Medicine

We are delighted to announce that Judy Liberman has been elected as a member of the National Academy of Medicine!

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Randomized study for treatment of COVID pneumonia in children and adults uses cystic fibrosis drug, dornase alfa (Pulmozyme)

Drug may break up 'neutrophil extracellular traps' or NETS, which contribute to lung inflammation and thicken mucus.

BOSTON - Researchers at Boston Children's Hospital and Brigham and Women's Hospital have launched a randomized, placebo-controlled clinical trial of dornase alfa (Pulmozyme) in patients with severe COVID-19 pneumonia and respiratory failure requiring mechanical ventilation. The study aims to enroll 60 adults and children (over age 3) admitted to intensive care units.

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Judy Lieberman elected to National Academy of Sciences

It is our great pleasure to announce that PCMM's Judy Lieberman has been elected as a member of the U.S. National Academy of Sciences!

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Fred Alt, Hidde Ploegh, and Richard Flavell named Distinguished Fellows of the American Association of Immunologists

The American Association of Immunologists has named PCMM Director and Senior Investigator Fred Alt, Charles A. Janeway Professor of Pediatrics and Professor of Genetics at Harvard Medical School and Howard Hughes Medical Institute Investigator at BCH, and PCMM Senior Investigator Hidde Ploegh as members of the Distinguished Fellows of American Association of Immunologists, Class of 2020. Also among the latest class of AAI Distinguished Fellows is PCMM Scientific Advisory Board member Richard Flavell, Sterling Professor of Immunobiology at Yale School of Medicine and Investigator of the Howard Hughes Medical Institute.

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Hao Wu and TJ Ha honored as 2020 Biophysical Society Fellows

The Biophysical Society has named Hao Wu, PCMM Senior Investigator and Asa and Patricia Springer Professor Biological Chemistry and Molecular Pharmacology and Professor of Pediatrics at Harvard Medical School, and Taekjip (TJ) Ha, the newest member of the PCMM Scientific Advisory Board and Bloomberg Distinguished Professor, Professor of Biophysics and Biophysical Chemistry, Professor of Biomedical Engineering, and Howard Hughes Medical Institute Investigator at Johns Hopkins School of Medicine, as 2020 Society Fellows.

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Sun Hur, PhDSun Hur promoted to Professor

The PCMM is most pleased to congratulate PCMM Investigator Dr. Sun Hur on her promotion to Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. She is also being proposed for an appointment as Professor of Pediatrics. Sun came to PCMM as a theoretical chemist and X-ray crystallographer, and here focused her lab upon a key question in immunology and biology more generally: how self vs. non-self nucleic acids are distinguished in the host cell to lead to appropriate innate immune responses.

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Chromatin loops unlock antibody class switching

Researchers in the laboratory of Frederick Alt of the Howard Hughes Medical Institute and Program in Cellular and Molecular Medicine (PCMM) at Children's Hospital Boston continue their groundbreaking work at the nexus of genetics and immunology, specifically the response of antigen-activated B cells to the enormous variety of possible threats, including bacteria, viruses, and parasites.

Two reports from the Alt Lab in Nature (the first in September 2019 and a second online on October 30, 2019, with a Nature “News and Views” covering both) present major advances in chromatin regulation, showing that two distinct types of antibody gene recombination, occurring at different developmental stages, both depend upon reeling long loops of chromatin past recombination centers to align substrate gene segments in the processes known as V(D)J recombination and class switch recombination (CSR).

Fred Alt Received AAI-BioLegend Herzenberg Award

Congratulations to Dr. Frederick W. Alt for receiving the BioLegend Herzenberg Award from the American Association for Immunologists (AAI). Established to honor the memory of AAI member Leonard A. Herzenberg Ph.D., this award recognizes investigator who has made outstanding for outstanding contributions to the field of Immunology in the area of B cell biology. This award is generously supported by BioLegend