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PCMM Research | Overview

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

Getting a grip on genetic loops

 

Announcements

Junior faculty candidate seminars

PCMM and the joint PCMM-HMS Department of Cell Biology faculty search committee are pleased to announce these upcoming seminars by our junior faculty search candidates. All seminars will be held in person from 11 a.m. to noon at the Armenise Amphitheater, Room 125 (D), and simultaneously broadcast as Zoom webinars.

Thursday, February 24
“Decoupling tissue repair from inflammation through cytokine engineering”
Robert Saxton, PhD, Garcia Lab, Stanford University School of Medicine
Host: Professor Jeffrey Moffitt
Zoom link for Saxton seminar | Passcode: 899132

Monday, February 28
“Probing the single-cell 3D genome architectural basis of neurodevelopment and aging in vivo”
Longzhi Tan, PhD, Deisseroth Lab, Stanford University
Host: Professor Tom Kirchhausen
Zoom link for Tan seminar | Passcode: 515300

Thursday, March 3
“Injury repair: a host response to homeostatic disruption”
Siqi Liu, PhD, Fuchs Lab, Rockefeller University
Host: Professor Susan Shao;
Zoom link for Liu seminar | Passcode: 359859

Monday, March 7
“The host strikes back: Strategies for evolutionary warfare with pathogens”
Jeannette Tenthorey, PhD, Malik Lab, Fred Hutchinson Cancer Research Center
Host: Professor Tobias Walther
Zoom link for Tenthorey seminar | Passcode: 030454

Please contact PCMM-recruitment@childrens.harvard.edu for questions and to request access to seminar recordings.

Michael Carroll and Arlene Sharpe elected Distinguished Fellows of AAI

Michael Carroll headshotArlene Sharpe headshotPCMM Senior Investigator Michael Carroll and PCMM Scientific Advisory Board member Arlene Sharpe were elected as members of the Class of 2022 of the Distinguished Fellows of the American Association of Immunologists!

This is among the highest honors bestowed by AAI, annually recognizing long-term (25 or more years) members for distinguished careers and outstanding scientific contributions, as well as their service to AAI and the immunology community; fellows bear the designation “DFAAI.” Distinguished Fellows of the AAI have “demonstrated one or more of the following: 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.”

Please join us in congratulating Mike and Arlene for this milestone accomplishment!

PCMM Irvington Fellows from left to right: Ryan Alexander, Hongli Hu, Rui Miao and Sherry Zhang

 

Four PCMM researchers win Irvington Fellowships in banner

Four PCMM postdoctoral researchers were honored in 2021 by the Cancer Research Institute. <a data-cke-saved-href=">Ryan Alexander of the Ploegh Lab was an inaugural recipient of the CRI Irvington Postdoctoral Fellowship to Promote Racial Diversity, and Hongli Hu of the Alt Lab, Rui Miao of the Lieberman Lab, and Qianxia (Sherry) Zhang of the Hur Lab were winners of the CRI Irvington Postdoctoral Fellowship.

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Ryan Alexander, a postdoctoral fellow in the laboratory of Hidde Ploegh, will explore a modular strategy of utilizing a combination of nanobody-based chimeric antigen receptor (nano-CAR) T cells and macrophages to target and overcome normally resistant pancreatic tumors in mice; these cells bear alpaca antibody-derived nanobodies, which are smaller and displayed more efficiently on the cell surface than antibodies and are designed to target proteins that are highly and selectively expressed by pancreatic tumors compared to healthy tissue, and are thus less likely to be recognized as “foreign” and attacked by the immune system.

Hongli Hu, an instructor in the laboratory of Fred Alt, will compare and contrast the long-range mechanisms in the context of higher-order chromatin structure used by antibody heavy and light chain loci to incorporate Vs into the V(D)J recombination reaction, which will provide major new insights into fundamental mechanisms that establish highly diverse primary antibody repertoires and how this process can go awry to generate genomic rearrangements in cancers of developing B cells, as well as inform new approaches to generate therapeutic human antibodies against cancer and other diseases.

Rui Miao, a postdoctoral fellow in the laboratory of Judy Lieberman, will investigate the role of granzyme M (GzmM), one of the most abundant and important granzymes in innate killer lymphocytes, in killer lymphocyte-driven pyroptotic killing of tumor cells and anti-tumor immunity mediated by gasdermin E (GSDME), a member of the pore-forming gasdermin protein family, aiming to uncover the molecular basis for tumor cell evasion and provide insights into how to harness the GzmM-GSDME-pyroptosis axis in the tumor microenvironment to ignite an effective immune response to immunologically cold tumors.

Sherry Zhang, a postdoctoral fellow in the laboratory of Sun Hur, will elucidate the molecular mechanism of transcription mediated by autoimmune regular (Aire), which drives autoreactive T cells to undergo clonal deletion or regulatory T cell differentiation and has been linked to impairment of antitumor immunity, mutations in which lead to multi-organ autoim;mune diseases, through functional analysis of its interactions with the co-activator CBP/P300 and genetic screen-based identification of its key downstream factors, with the aim of identifying potential therapeutic targets for manipulating self-tolerance, autoimmune syndromes, and antitumor immunity.

Congratulations to all, PCMM is proud of you!

 

Sun Hur headshot

Sun Hur wins Paul Marks Prize

We are very happy to announce that Sun Hur is a 2021 recipient of the Memorial Sloan Kettering Cancer Center’s Paul Marks Prize for Cancer Research! From MSKCC’s web site: "The prize, named in honor of MSK's past President Emeritus, the late Paul Marks, MD, recognizes a new generation of leaders in cancer research who are making significant contributions to the understanding of cancer or are improving the treatment of the disease through basic or clinical research."

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The citation states, "Dr. Hur studies the innate immune system — in particular, how host cells distinguish between self and non-self nucleic acids. She has used her expertise in chemistry and structural biology to address vital questions in this field. Her research has led to the discovery of mechanisms for key signaling pathways that play a role in both the immune response and pathogenesis of a wide range of immune disorders. It also can be applied to the development of new kinds of cancer immunotherapy." Congratulations to Sun!

 

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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!

 

Hao Wu headshotAkiko Iwasaki headshot

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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FrederickAltRichard headshotHidde-Ploegh-headshot

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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TJ Ha headshotHao Wu Headshot

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 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

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Fred Alt, a blond man wearing a blue polo shirt, smiles at the camera.