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In the News: AIMBE, HERO Registry, Crazy 8, Blinatumomab, Lung Development

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March 19, 2021
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limjr [at] chop.edu (By Jillian Lim)

With spring arriving this weekend (at least on our calendars, if not the weather forecast), it's an ideal time to read about how far some of our research at Children's Hospital of Philadelphia has come — and what we can look forward to in the future. A multi-site registry, first established at the beginning of the COVID-19 pandemic to support healthcare workers, publishes new findings, while cancer researchers offer positive insights into a treatment for a difficult-to-treat, high-risk pediatric cancer, and one scientist celebrates induction into the American Institute for Medical and Biomedical Engineering. Keep reading to learn more about these headlines and others.

AIMBE Inducts Hao Huang, PhD, as Fellow

We are proud to congratulate Dr. Huang, scientist and faculty director for the Small Animal Imaging Facility at CHOP, for his election to the distinguished American Institute for Medical and Biomedical Engineering (AIMBE)'s College of Fellows. Dr. Huang, who is also an associate professor in Radiology at the University of Pennsylvania, will be formally inducted at a ceremony held during AIMBE's 2021 Annual Event, March 26.

AIMBE's College of Fellows is comprised of the country's top two percent of medical and biomedical engineers, according to a press release, with previous fellows having been awarded the Nobel Prize, the Presidential Medal of Science, and the Presidential Medal of Technology.

Peers and members of the College of Fellows nominated, reviewed, and elected Dr. Huang for his "contributions to the development and applications of innovative (magnetic resonance) methods to study the developing brain." On Cornerstone, we previously covered Dr. Huang's discovery that whole-brain cortical microstructure at birth, quantified by diffusion magnetic resonance imaging, may predict cognitive and language functions assessed at age 2. The findings are significant because early intervention for neuropsychiatric disorders can potentially improve outcomes in children with autism spectrum disorder and other developmental disorders.

HERO Registry Highlights COVID-19's Impact on Healthcare Workers

New results from the Healthcare Worker Exposure Response and Outcomes (HERO) Registry shed light on the COVID-19 pandemic's early impact on U.S. healthcare workers. The findings, which were recently published in the Journal of General Internal Medicine, report that though healthcare workers are at a high risk for COVID-19 exposure, rates of COVID-19 illness were low. Additionally, the greater risk of COVID-19 infection among race/ethnicity minorities reported in the general population is also seen in healthcare workers.

As reported previously on Cornerstone, the HERO Registry is a multi-institute network whose purpose is to better understand the needs, experiences, and priorities of healthcare workers during the pandemic by enrolling participants and collecting information. A total of 14,600 healthcare workers participated in the current study, with 74.7 percent working in hospitals, 7.4 percent in outpatient clinics, and 18.2 percent in other settings throughout the U.S. Participants completed a survey that addressed several measures, including COVID-19 exposure, viral and antibody testing, diagnosis of COVID-19, job burnout, and physical and emotional distress.

In the publication, Christopher Forrest, MD, PhD, chair of the HERO Registry sub-committee and director of the Center for Applied Clinical Research at CHOP, and his co-investigators report that the registry will continue to monitor changes in healthcare worker well-being during the pandemic.

"This is a community that stands ready and willing to be involved in studies that can help address their needs during this pandemic," Dr. Forrest said in our Cornerstone story. "We're in COVID time now, and we need to be ready. I want tools to help healthcare workers available in weeks not years. That's one of the values of this registry."

Read more about the findings.

CHOP Researchers Awarded ALSF Crazy 8 Grant

A team of researchers that includes our Division of Oncology's Yael Mossé, MD, John Maris, MD, and Ophir Shalem, PhD, received a grant from Alex's Lemonade Stand Foundation (ALSF)'s Crazy 8 Initiative. The initiative, first established in 2018, provides support for projects across 15 institutions using cutting-edge technology to address critical issues in childhood cancer research. ALSF awarded a total of more than $18.5 million to Crazy 8 researchers this year, the largest funding commitment from ALSF to date.

Led by Dr. Mossé, the CHOP team is collaborating with investigators from various institutions to develop a drug that targets the transcription factor MYCN, which drives aggressive pediatric cancers such as neuroblastoma and medulloblastoma. The researchers will use cutting-edge technology, targeted degradation, to create the drug that aims to trick the cancer cells into dissolving MYCN.

Learn more about ALSF's Crazy 8 Initiative.

Targeted Treatment Shows Benefit for High-Risk B-ALL

Cancer Center researchers at CHOP, in collaboration with 155 other hospitals in the Children's Oncology Group, showed that the drug blinatumomab, a bispecific T-cell engaging antibody, is less toxic than chemotherapy for high-risk relapsed B-cell acute lymphoblastic leukemia (B-ALL). The researchers published their findings in JAMA, suggesting blinatumomab as the standard of care for patients with the high-risk, difficult-to-treat cancer.

In the randomized phase 3 clinical trial, the researchers had enrolled patients 1 to 30 years old who were experiencing their first B-ALL relapse. Those patients in the blinatumomab cohort showed strong results over those in the multiagent chemotherapy cohort: The two-year overall survival was 71.3 percent for the former and 58.4 percent for the latter. Those who received chemotherapy experienced high rates of serious adverse events, such as infection, febrile neutropenia, and sepsis.

"This study shows that blinatumomab can replace chemotherapy in certain subsets of B-ALL because it is less toxic and leads to better outcomes," said co-senior author Stephen P. Hunger, MD, chief of the Division of Oncology and director of the Center for Childhood Cancer Research. "Additional studies will examine this therapy in other disease stages of B-ALL to see if it has a similar benefit."

Learn more in the press release.

Study Describes How Key Lung Part Forms at the Cellular Level

CHOP researchers revealed how the lung alveolus, a critical part of the lung, forms and allows newborns to breathe air at a cellular level. Publishing their findings in the journal Science, the new insights allow scientists to better understand how to develop therapies and potentially regenerate this critical tissue when injured.

During the transition from embryo to newborn, the alveolar region of the lung refines its primary function of exchanging gas, including ridding the body of carbon dioxide. Previously, however, little was known about how this happens at a cellular and genomic level. Using a multimodal approach to investigate the intercellular relationships driving the alveolus' formation, the researchers discovered that alveolar type 1 (AT1) epithelial cells, which form the outer layer of the alveolus tissue, represent a signaling hub that coordinates cell development, particularly in the transition to air breathing. The team also demonstrated that the lineage of AT1 cells align with those cell types involved in tissue remodeling, and that AT1-restricted ligands are needed to form these cell types and the alveolus.

"Our study reveals the complexity of the cell-types and their extensive communication with one another as they form this critical part of the lung," first author Jarod Zepp, PhD, said in a CHOP press release. Dr. Zepp is a research faculty member of the Division of Pulmonary and Sleep Medicine at CHOP. "This research provides us with vital clues on how we might be able to repair damaged tissue at a cellular level."

Read more in the press release.

ICYMI

Catch up on our headlines from our March 5 In the News:

  • Two Treatment Strategies for Tetralogy of Fallot Offer Potential Benefits
  • CPR Researchers Ranked High for Number of Published Articles
  • Oxygen Therapy Timing in Neonatal Period Linked to Influenza Susceptibility
  • FARE Designates CHOP as Data Coordination Center
  • Stroke is an Infrequent Complication in Children With SARS-CoV-2

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