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Billie Lou Short and Kurt Newman at Research and Education Week

Research and Education Week honors innovative science

Billie Lou Short and Kurt Newman at Research and Education Week

Billie Lou Short, M.D., received the Ninth Annual Mentorship Award in Clinical Science.

People joke that Billie Lou Short, M.D., chief of Children’s Division of Neonatology, invented extracorporeal membrane oxygenation, known as ECMO for short. While Dr. Short did not invent ECMO, under her leadership Children’s National was the first pediatric hospital to use it. And over decades Children’s staff have perfected its use to save the lives of tiny, vulnerable newborns by temporarily taking over for their struggling hearts and lungs. For two consecutive years, Children’s neonatal intensive care unit has been named the nation’s No. 1 for newborns by U.S. News & World Report. “Despite all of these accomplishments, Dr. Short’s best legacy is what she has done as a mentor to countless trainees, nurses and faculty she’s touched during their careers. She touches every type of clinical staff member who has come through our neonatal intensive care unit,” says An Massaro, M.D., director of residency research.

For these achievements, Dr. Short received the Ninth Annual Mentorship Award in Clinical Science.

Anna Penn, M.D., Ph.D., has provided new insights into the central role that the placental hormone allopregnanolone plays in orderly fetal brain development, and her research team has created novel experimental models that mimic some of the brain injuries often seen in very preterm babies – an essential step that informs future neuroprotective strategies. Dr. Penn, a clinical neonatologist and developmental neuroscientist, “has been a primary adviser for 40 mentees throughout their careers and embodies Children’s core values of Compassion, Commitment and Connection,” says Claire-Marie Vacher, Ph.D.

For these achievements, Dr. Penn was selected to receive the Ninth Annual Mentorship Award in Basic and Translational Science.

The mentorship awards for Drs. Short and Penn were among dozens of honors given in conjunction with “Frontiers in Innovation,” the Ninth Annual Research and Education Week (REW) at Children’s National. In addition to seven keynote lectures, more than 350 posters were submitted from researchers – from high-school students to full-time faculty – about basic and translational science, clinical research, community-based research, education, training and quality improvement; five poster presenters were showcased via Facebook Live events hosted by Children’s Hospital Foundation.

Two faculty members won twice: Vicki Freedenberg, Ph.D., APRN, for research about mindfulness-based stress reduction and Adeline (Wei Li) Koay, MBBS, MSc, for research related to HIV. So many women at every stage of their research careers took to the stage to accept honors that Naomi L.C. Luban, M.D., Vice Chair of Academic Affairs, quipped that “this day is power to women.”

Here are the 2019 REW award winners:

2019 Elda Y. Arce Teaching Scholars Award
Barbara Jantausch, M.D.
Lowell Frank, M.D.

Suzanne Feetham, Ph.D., FAA, Nursing Research Support Award
Vicki Freedenberg, Ph.D., APRN, for “Psychosocial and biological effects of mindfulness-based stress reduction intervention in adolescents with CHD/CIEDs: a randomized control trial”
Renee’ Roberts Turner for “Peak and nadir experiences of mid-level nurse leaders”

2019-2020 Global Health Initiative Exploration in Global Health Awards
Nathalie Quion, M.D., for “Latino youth and families need assessment,” conducted in Washington
Sonia Voleti for “Handheld ultrasound machine task shifting,” conducted in Micronesia
Tania Ahluwalia, M.D., for “Simulation curriculum for emergency medicine,” conducted in India
Yvonne Yui for “Designated resuscitation teams in NICUs,” conducted in Ghana
Xiaoyan Song, Ph.D., MBBS, MSc, “Prevention of hospital-onset infections in PICUs,” conducted in China

Ninth Annual Research and Education Week Poster Session Awards

Basic and Translational Science
Faculty:
Adeline (Wei Li) Koay, MBBS, MSc, for “Differences in the gut microbiome of HIV-infected versus HIV-exposed, uninfected infants”
Faculty: Hayk Barseghyan, Ph.D., for “Composite de novo Armenian human genome assembly and haplotyping via optical mapping and ultra-long read sequencing”
Staff: Damon K. McCullough, BS, for “Brain slicer: 3D-printed tissue processing tool for pediatric neuroscience research”
Staff: Antonio R. Porras, Ph.D., for “Integrated deep-learning method for genetic syndrome screening using facial photographs”
Post docs/fellows/residents: Lung Lau, M.D., for “A novel, sprayable and bio-absorbable sealant for wound dressings”
Post docs/fellows/residents:
Kelsey F. Sugrue, Ph.D., for “HECTD1 is required for growth of the myocardium secondary to placental insufficiency”
Graduate students:
Erin R. Bonner, BA, for “Comprehensive mutation profiling of pediatric diffuse midline gliomas using liquid biopsy”
High school/undergraduate students: Ali Sarhan for “Parental somato-gonadal mosaic genetic variants are a source of recurrent risk for de novo disorders and parental health concerns: a systematic review of the literature and meta-analysis”

Clinical Research
Faculty:
Amy Hont, M.D., for “Ex vivo expanded multi-tumor antigen specific T-cells for the treatment of solid tumors”
Faculty: Lauren McLaughlin, M.D., for “EBV/LMP-specific T-cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation”

Staff: Iman A. Abdikarim, BA, for “Timing of allergenic food introduction among African American and Caucasian children with food allergy in the FORWARD study”
Staff: Gelina M. Sani, BS, for “Quantifying hematopoietic stem cells towards in utero gene therapy for treatment of sickle cell disease in fetal cord blood”
Post docs/fellows/residents: Amy H. Jones, M.D., for “To trach or not trach: exploration of parental conflict, regret and impacts on quality of life in tracheostomy decision-making”
Graduate students: Alyssa Dewyer, BS, for “Telemedicine support of cardiac care in Northern Uganda: leveraging hand-held echocardiography and task-shifting”
Graduate students: Natalie Pudalov, BA, “Cortical thickness asymmetries in MRI-abnormal pediatric epilepsy patients: a potential metric for surgery outcome”
High school/undergraduate students:
Kia Yoshinaga for “Time to rhythm detection during pediatric cardiac arrest in a pediatric emergency department”

Community-Based Research
Faculty:
Adeline (Wei Li) Koay, MBBS, MSc, for “Recent trends in the prevention of mother-to-child transmission (PMTCT) of HIV in the Washington, D.C., metropolitan area”
Staff: Gia M. Badolato, MPH, for “STI screening in an urban ED based on chief complaint”
Post docs/fellows/residents:
Christina P. Ho, M.D., for “Pediatric urinary tract infection resistance patterns in the Washington, D.C., metropolitan area”
Graduate students:
Noushine Sadeghi, BS, “Racial/ethnic disparities in receipt of sexual health services among adolescent females”

Education, Training and Program Development
Faculty:
Cara Lichtenstein, M.D., MPH, for “Using a community bus trip to increase knowledge of health disparities”
Staff:
Iana Y. Clarence, MPH, for “TEACHing residents to address child poverty: an innovative multimodal curriculum”
Post docs/fellows/residents:
Johanna Kaufman, M.D., for “Inpatient consultation in pediatrics: a learning tool to improve communication”
High school/undergraduate students:
Brett E. Pearson for “Analysis of unanticipated problems in CNMC human subjects research studies and implications for process improvement”

Quality and Performance Improvement
Faculty:
Vicki Freedenberg, Ph.D., APRN, for “Implementing a mindfulness-based stress reduction curriculum in a congenital heart disease program”
Staff:
Caleb Griffith, MPH, for “Assessing the sustainability of point-of-care HIV screening of adolescents in pediatric emergency departments”
Post docs/fellows/residents:
Rebecca S. Zee, M.D., Ph.D., for “Implementation of the Accelerated Care of Torsion (ACT) pathway: a quality improvement initiative for testicular torsion”
Graduate students:
Alysia Wiener, BS, for “Latency period in image-guided needle bone biopsy in children: a single center experience”

View images from the REW2019 award ceremony.

Children’s National Chief of Allergy and Immunology helps move gene therapy forward

Catherine Bollard

Catherine Bollard, M.D., MBChB, Chief of the Division of Allergy and Immunology, recently shared her expertise on an FDA panel that unanimously expressed its support for a pediatric cancer T-cell therapy called CTL019.

On July 12, 2017, a U.S. Food and Drug Administration advisory committee unanimously expressed its support for CTL019 – a pediatric cancer T-cell therapy. If the FDA follows the advice from the 10-member Oncologic Drug Advisory Committee (ODAC) – which included Children’s National Health System’s Catherine Bollard, M.D., MBChB, Chief of the Division of Allergy and Immunology and Director of the Program for Cell Enhancement and Technologies for Immunotherapy – CTL019 will become the first gene therapy to hit the market.

“Many of these children with recurrent cancer are out of other options to treat their illness,” said Dr. Bollard. “We are encouraged by these findings and the potential for this therapy to improve outcomes and quality of life.”

CTL019 is a chimeric antigen receptor (CAR) T-cell therapy, comprised of genetically modified T cells that target CD19, an antigen expressed on the surface of B cells. Also known as tisagenlecleucel, the therapy targets a single type of cancer called acute lymphoblastic leukemia and was created by Novartis.

In clinical trials, CTL019 showed unparalleled effectiveness. Of the 68 patients who received the drug, 52 responded almost immediately, and their cancer disappeared within the first three months. Seventy-five percent of those patients remained cancer-free six months after treatment. The therapy has one main side effect: an immune reaction called cytokine release syndrome, which can be deadly, with extended spiking fevers and other symptoms.

However, because of CTL019’s high efficacy, FDA scientists asked the ODAC panel to focus on the therapy’s safety and manufacturing challenges rather than whether or not it works.

Several committee members, including Dr. Bollard, expressed apprehension about the T-cell subpopulations’ heterogeneity, which could affect safety and efficacy. Another issue for consideration by the ODAC panel was the long-term side effects of CTL019 and the possibility that the T-cell modification could go awry, causing secondary cancers in the future.

Despite these concerns, the committee concluded that the strong efficacy data and the near-term benefits of CAR-T therapy more than tipped the scales in favor of the therapy. ODAC members were also pleased with Novartis’ plan to minimize risk, which includes limiting CTL019 distribution to selected centers with CAR T-cell therapy experience, and extensive, long-term post-marketing surveillance plans.

The FDA is not required to follow the ODAC panel’s advice when making its final decision, but it often does so. A final decision by the FDA is anticipated by late September.

Read more about the story in the Philadelphia Inquirer, Medpage Today and Healio.com.

Mark Batshaw

Gene therapy’s slow rebirth

Mark Batshaw

A speech by outgoing American Pediatric Society President Mark L. Batshaw, M.D., explored the impact of a single clinical trial on the entire field.

Gene therapy – delivering genetic material into patients’ cells as a way to treat or cure their diseases – has immense promise to alleviate or end many lifelong and deadly conditions. This treatment has so much potential that it was a heavy focus of research and research dollars around the world in the 1980s and 1990s.

However, many of these efforts came to a screeching halt in 1999 when a teenaged patient named Jesse Gelsinger died in a gene therapy trial aimed at curing a disease called ornithine transcarbamylase deficiency, a urea cycle disorder. Gelsinger’s death triggered a number of investigations, halted gene therapy trials in the United States, and severely restricted financial support from federal, foundation and industry funders.

The tragedy also spurred Mark L. Batshaw, M.D., one of the clinical trial investigators and newly named Chief Academic Officer at Children’s National Health System, to turn in his resignation. The chief executive at the time declined to accept it, instead naming an outside panel to investigate Dr. Batshaw’s role in a study marred by conflicts of interest, delays in updating patient consent forms, lack of adherence to the study protocol and ineffective team leadership.

As Dr. Batshaw passed the gavel to the next president of the American Pediatric Society during the Pediatric Academic Societies’ annual meeting this spring, he told attendees of his Presidential Address that “not a day goes by that I don’t think of Jesse Gelsinger and his family and hope that the work our team has continued will honor him by eventually achieving success with gene therapy.” In an act of altruism, 18-year-old Jesse Gelsinger had joined the trial with the aim of helping other kids suffering from metabolic disorder.

Dr. Batshaw recognizes that his is an unusual choice, speaking about his “greatest professional failure” when predecessors have used their addresses to speak exclusively about scientific accomplishments.

“Because I was a principal, I think telling this story first of all says, hey look, this guy who is president of this organization, who has had a significant career, is willing to talk openly about a failure and how he dealt with it and how the field dealt with that failure,” Dr. Batshaw says. “Secondly, the field of gene therapy right now is starting to explode. It’s telling two different stories in an integrated way: One is of a great personal failure – and failure of an entire field. And the recovery from that, and what the future will be for a technology that holds great promise.”

More than 1,000 gene therapy trials are currently underway, 23 of them at Phase III, the pivotal stage that makes or breaks approval by the Food and Drug Administration (FDA). Dr. Batshaw estimates about a dozen of those are likely to demonstrate robust enough results to progress to a formal application for FDA approval. “After a period of virtually no growth in gene therapy trials from 2000 to 2013, there has been a marked upswing in the past two to three years,” he says.

Children’s National is a study site for one of those clinical trials, a Phase I/II adenoassociated virus (AAV)-mediated gene therapy for late-onset ornithine transcarbamylase (OTC) deficiency. Children with urea cycle disorders have enzyme deficiencies that leave them unable to adequately dispose of waste nitrogen. Often as newborns, they develop severely elevated ammonia in their brains leading to encephalopathy, an often fatal condition. The Phase I work will test escalating doses in three patients for safety. The Phase II work will explore whether the gene therapy improves outcomes like lowering ammonia levels and improving patients’ ability to convert ammonia to urea. (A precursor study in an experimental model was among the most impactful research papers published by Children’s National authors in 2016.)

“So, for both our group’s program – and viral-delivered gene therapy in general – there has been a rebirth after the disastrous outcome of the initial adenovirus trial in OTC deficiency,” Dr. Batshaw said in his prepared remarks. “This resurgence has likely been fueled by improved viral vectors, especially AAVs, and an improved economy and industry investment. The future of gene therapy is likely to be enhanced by new genetic therapy platforms including RNA interference as a means of vertically transmitted gene regulation and the CRISPR gene-editing technology. It will also be impacted by the results of the trials that will be completed in the next few years, especially those using AAV vectors in hemophilia A and B, spinal muscular atrophy and leukemia.”

Looking forward 10 years, Dr. Batshaw is hopeful that gene therapy will become part of the therapeutic tools routinely used to help patients who suffer from rare disease and cancer. Making that next leap forward will be powered by innovative research, including work by colleagues at Children’s National. Among the presenters at PAS2017, the world’s largest pediatric research meeting, were more than 100 Children’s presenters, speakers and moderators.

“It makes me very proud that there are so many clinicians who are also scientists who are not satisfied with simply doing things the way they have always been doing it but constantly questioning how can we do things better for our children?” Dr. Batshaw says. “Our whole focus at Children’s National is caring for children, and that means caring for them the very best way possible and not being satisfied with current therapy if it’s not curative.”