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College of Physicians Induction, CGT Collaborative Awardees, Bone Marrow Atlas

Published on May 24, 2024 in Cornerstone Blog · Last updated 2 weeks 6 days ago
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In the News

 

May is award season at Children's Hospital of Philadelphia, so help us congratulate seven researchers on receiving grants for their cell and gene therapy work, as well as Dr. Sue Furth for being inducted into the College of Physicians of Philadelphia. Another study received funding to manufacture painless wound dressings, and CHOP researchers put together a first-of-its-kind bone marrow atlas. Discover these stories and more below.

CSO Dr. Susan Furth Inducted into the College of Physicians of Philadelphia

Susan L. Furth
Susan Furth, MD, PhD

The College of Physicians of Philadelphia inducted new fellows Friday, May 10, including our Executive Vice President and Chief Scientific Officer Susan Furth, MD, PhD. She was nominated by President and Chief Executive Officer Madeline Bell, and Lucy Rorke-Adams, MD.

"It was an honor to be nominated by our CEO Madeline Bell and Lucy Rorke-Adams, a remarkable neuropathologist who served as a chair of the Department of Pathology at CHOP before she retired," Dr. Furth said. "The College is a historic organization, and I am privileged to be a member."

The College of Physicians of Philadelphia acts as a medical, educational, and cultural institution to advance medicine through a unique blend of the arts and sciences since 1787. Fellows must represent the diversity of the Philadelphia community they serve while inspiring future generations with meaningful contributions to patient care.

Congratulations to Dr. Furth!

Cell and Gene Therapy Collaborative Announce FY25 Grant Recipients

The Cell and Gene Therapy Collaborative, led by Dr. Furth and Joseph St. Geme, MD, strives to increase the number of potential new pediatric cell and gene therapies resulting from CHOP-led research. Each year, they offer Seed Grants to promote early-stage development of ideas in engineered cell therapy or gene therapy, and Acceleration Grants to support progress of later-stage preclinical programs to advance first-in-human testing.

Congratulations to this year's winners!

Cell and Gene Therapy Seed Grants

  • In their study, titled, "CAR T-cell targeting of heteropentameric complexes in neuroblastoma," Kristopher Bosse, MD, and Sharon Diskin, PhD, will explore two differentially expressed cell surface receptors found on neuroblastoma cells that will define their mechanisms of overexpression and help determine if this could be a new target for appropriately engineered CAR T cells.
  • Ethan Goldberg, MD, PhD, and Jerome Clatot, PhD, will examine genetic variants in brain-expressed sodium channel genes that cause a variety of neurological conditions to determine if engineered sodium channel peptide fragments delivered via AAV vector can correct the channel pathway function.
  • Evan Weber, PhD, aims to optimize the safety and efficacy of CAR T-cell therapy by developing a drug-regulatable CAR system that could offer specific dosing regimens that would more precisely control CAR expression levels to reduce toxicity.
  • With his project, "Hemophilia A gene therapy with a high-specific-activity factor VIII variant," Ben Samelson-Jones, MD, PhD will look to address concerns over durability and low deficient coagulation factor VIII (FVIII) levels in currently available therapies by characterizing and evaluating a novel FVIII variant with high activity delivered via an AAV vector.

Cell and Gene Therapy Accelerated Grant

  • Lindsey George, MD, will perform investigational new drug-enabling studies on the AAV vector that encodes engineered gain-of function FVIII variant, FVIII-QQ, to develop a hemophilia A gene therapy that normalizes FVIII function at low levels of FVIII-QQ expression to durably correct phenotype.

Learn more about the Cell and Gene Therapy Collaborative's funding initiatives.

Bone Marrow Atlas Offers First of Its Kind Biomolecular Breakdown of Cells

Kai Tan
Kai Tan, PhD

A new study published in Cell is the first of its kind to provide a human bone marrow atlas useful for investigations of the cellular interactions that drive healthy and diseased hematopoiesis. The study is also part of the broader Human BioMolecular Atlas Program that helps researchers develop the next generation of molecular analysis technologies and computational tools to create tissue maps and functional atlases for human cells.

"For the first time, we will have a comprehensive framework to view the full gene expression and spatial organization of bone marrow cells," said senior study author Kai Tan, PhD, director of the Center for Single Cell Biology. "Although our paper is foundational, we envision the atlas will be used to develop new diagnostic tests, identify new CAR-T or other therapeutic targets, and discover spatial biomarkers of disease."

Researchers from CHOP and the Perelman School of Medicine at the University of Pennsylvania comprehensively profiled adult human bone marrow using single-cell RNA sequencing to capture the full gene expression profile of tens of thousands of individual cells. They noted at least nine subsets of non-hematopoietic cells, which produce factors known to be important in human blood production.

Using co-detection by indexing (CODEX) to spatially profile more than 1.2 million cells and the manual annotation of thousands of cells and structures, researchers revealed that healthy bone marrow has distinct spatial organization, and fat cells are more closely associated with blood-producing cells than previously understood.

Learn more in this CHOP news release.

Genetics, Environment, Health Disparities Linked to Increased Stress in Adolescents

Ran Barzilay
Ran Barzilay, MD, PhD

The impact of environmental exposure on stress is often overlooked in studies because it is difficult to quantify, but understanding how the exposome contributes to health disparities could provide better framework for interventions and inform health disparity research, as observed by CHOP researchers in a recent publication.

As the first of its kind, a new study has validated allostatic load (AL), or cumulative genetic and environmental stress on the body, as measurable in teens, revealing childhood adversity correlates with increased stress and mental health challenges during adolescence. The results were published in Nature Mental Health.

"The findings expand existing literature suggesting a mediating role of AL from childhood adversity to adult mental health and support the hypothesis that AL could be a mechanism that contributes to health disparities," said lead study author, Ran Barzilay, MD, PhD, a psychiatrist in the Youth Suicide Prevention, Intervention and Research Center. "Critically, we show evidence of disparities in AL at an early age, well before expected onset of many chronic medical illnesses."

To quantify AL, researchers analyzed data from more than 5,000 diverse youth, averaging 12 years old, from the longitudinal Adolescent Brain Cognitive Development Study. Using measurements for body mass index and blood pressure among others, they calculated a latent AL score that also considered exposomic (environmental impact) risks through lifestyle factors like diet, exposure to abuse, poverty, and pollutants before age 11. Genetic risk was quantified by using polygenic risk scores for metabolic issues such as Type 2 diabetes, and psychiatric conditions such as major depressive disorder.

Learn more in this CHOP news release.

Manufacturing PA Innovation Program Awards Wound Dressing Research

Alex Tucker, MD

Alex Tucker, MD

A new type of wound dressing can resolve the common occurrence of painful or uncomfortable removal by dissolving in water, as proposed by CHOP and Penn researchers in recently awarded funding.

"Dressing removal from sensitive or hair-covered skin, like the head or face, is painful to patients and stressful to their families," said Alex Tucker, MD, an attending neurosurgeon at CHOP. "This research aims to create a next-generation wound dressing that is stronger than any currently available tissue adhesive but is reversible in water."

The Pennsylvania Department of Community and Economic Development's Manufacture PA Innovation Program awarded $140,000 in funding to Dr. Tucker and his collaborator, Shu Yang, department chair of the Materials Science and Engineering at the University of Pennsylvania for their work, "A Next-generation, painless wound dressing for acute wounds in children and those with delicate skin."

Current tissue adhesives applied to the scalp to dress wounds can either take weeks to fall off, pull out the patient's hair, or need to be cut out once the wound is healed. To address this issue, Dr. Tucker and Yang developed a hydrogel-based tissue adhesive that demonstrates quality adhesion strength despite its ease of removal after the dressing gets wet. Working with a Pennsylvania-based industrial partner, Dr. Tucker and Yang aim to manufacture dressings that will be flexible, painless, and biocompatible.

"This grant will support our work at the bench and in translational models to test our wound dressing with the hope of eventually using on the wounds of the patients we treat," Dr. Tucker said.

The Manufacturing PA Innovation Program supports manufacturing research collaborations between accredited PA colleges, universities, and PA manufacturers. The goal of the program is to enable these institutions to seamlessly bring their capabilities to bear to support industrial innovation and position the Commonwealth at the forefront of the next wave of manufacturing.

Surgeon-in-Chief Dr. N. Scott Adzick Wins 2024 Robert E. Gross Award

N. Scott Adzick
N. Scott Adzick, MD, MMM, FACS, FAAP

The American Pediatric Surgical Association awarded N. Scott Adzick, MD, Surgeon-in-Chief at CHOP, the 2024 Robert E. Gross Award for Excellence in Pediatric Research and Achievement at its annual meeting in Phoenix, Arizona.

"I was deeply touched to learn of this prestigious recognition," said Dr. Adzick, who is also the C. Everett Koop Professor of Pediatric Surgery at CHOP and a professor of Surgery, Obstetrics and Gynecology at the University of Pennsylvania School of Medicine. "It's a privilege to be part of the legacy of Robert E. Gross, MD, who had a pioneering commitment to innovation, compassion, and excellence in the field of pediatric surgery."

The award recognizes a seminal contribution by an individual who has made a major impact on pediatric surgery, and whose innovative contributions have resulted in a significant change in how pediatric surgeons manage a particular problem. Since founding and directing the Richard D. Wood Jr. Center for Fetal Diagnosis and Treatment in 1995 — one of the world's largest and most comprehensive fetal programs — Dr. Adzick and his colleagues have cared for more than 32,000 expectant mothers from every state and more than 70 countries, performing more than 2,400 life-changing fetal surgeries.

As a persistent advocate for medical progress, Dr. Adzick was also the driving force behind the world's first birth facility exclusively for mothers carrying babies with known birth defects. He has had National Institutes of Health grant support for more than 30 years, contributing more than 600 peer-reviewed publications to help advance the medical community's approach to pediatric and fetal surgery.

Congratulations to Dr. Adzick!

Learn more about his work in this CHOP press release.

CHOP Attending Physician Shares Cytokine IL-18 Research

Scott W. Canna, MD
Scott Canna, MD

The Immunology Podcast on Apple Podcasts hosted attending physician in the Division of Rheumatology and the Immune Dysregulation Program, Scott Canna, MD, to discuss the role of cytokine IL-18 in auto- and hyper-inflammatory diseases.

"The Immune Dysregulation Program at CHOP is an amazing resource of interested clinicians who run individual research programs that offer great training and learning opportunities," Dr. Canna said in the podcast. "It also provides the necessary scaffolding for natural history studies and biomarker validation."

IL-18 is an inflammatory cytokine present in almost every barrier epithelial cell, such as skin and the intestines, that may predispose people to macrophage activation syndrome due to its ability to amplify T cell responses. Macrophage activation syndrome, a potentially life-threatening condition, most commonly occurs in children with systemic juvenile idiopathic arthritis, triggering symptoms like high fever and liver dysfunction.

The International Cytokine and Interferon Society also highlighted Dr. Canna and his research in a profile piece in their newsletter, Signals. He discussed his lab's work modeling T-cell immune synapse to better understand hyperinflammatory syndromes, as well as some of the best career advice he's received: "It's every bit as hard as it looks, but there's nothing more interesting than being in research."

ICYMI

Catch up on our headlines from our May 10 In The News:

  • American Thoracic Society Recognizes Martha Curley, RN, PhD, FAAN
  • Healthcare Providers Critical to Autistic Adolescents Preparing for Adulthood
  • Gene Editing Successful for Two Patients with Inherited Blindness
  • American Gastroenterological Association Honors Dr. Kathryn Hamilton
  • ASGCT Annual Meeting Welcomes CHOP Innovators
  • CHOP Researchers at PAS 2024 in Toronto
  • Researchers Identify Causal Genetic Variant Linked to Common Childhood Obesity

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