The Manton Center | Pilot Project Award

The Pilot Project award is given to a Boston Children’s Hospital faculty member to support new high-risk/high-yield projects that require the development of preliminary data or proof of concept studies in order to attract longer-term funding from the National Institutes of Health and other mainstream funding agencies.


2020 Pilot Project Awardees

Heather Olson, MD, MS

Project title: Genetic variants in inflammatory epilepsy: Rasmussen Encephalitis and FIRES

Rasmussen Encephalitis (RE) and Febrile Infection Epilepsy Syndrome (FIRES) are two rare devastating disorders that occur in children resulting in a severe seizure disorder not responding to medications along with additional neurological deficits. Additional deficits may include learning and behavioral problems, muscle weakness, and swallowing or vision difficulties for example. The underlying cause for these disorders is unknown. This pilot study seeks to investigate underlying genetic causes for these two rare and severe disorders with inflammatory components. Understanding the underlying biology could lead to better treatments in the future.

Amy O'Connell, MD, PhD

Amy O'Connell, MD, PhD

Project title: T Cell Receptor Repertoire Sequencing Enhances Specificity of Newborn Screening for SCID in Premature Infants

Infants born prematurely have abnormal development of several organ systems, leading to orphan diseases of the eyes (retinopathy of prematurity), lungs (chronic lung disease), and other systems. Our research has shown that some premature infants may also develop a disease of their immune system, specifically impacting the development of their T cells. Some former premature babies have low numbers of T cells, but it’s hard to know if the function of the T cells is impaired because the traditional tests are not accurate in premature infants. For this pilot study, we will use a technique that assesses how many diverse T cell receptors are in a blood sample from these infants. If T cells are functioning normally, there will be a diverse set/repertoire of these receptors. This will help us to determine whether some premature infants have abnormal T cell development due to their prematurity. It may also improve newborn screening for another orphan disease, severe combined immunodeficiency (SCID), by giving us an easier way to check T cell activity during prematurity, as traditional tests often give false-positive results in premature infants.

Anne O'Donnell, MD, PhD

Anne O'Donnell-Luria, MD, PhD

Project title: Investigating the contribution of non-coding genetic changes to unsolved cases

Despite improvements in our ability to read the human genome, our understanding of how changes in the genome impact human disease remains limited. For example, although we know that disease-causing genetic changes can be located throughout the genome, current genetic testing is largely limited to only 1% of the human genome, which is the portion that codes for proteins. By contrast, genetic changes in the other 99% of the genome that alter when and where these proteins are produced are routinely ignored during genetic testing due to our poor ability to interpret their functional impact. This limitation hampers our ability to diagnose and provide targeted therapies for our patients. In this proposal, we aim to improve the diagnosis of patients with rare disorders by leveraging a novel method that determines whether a genetic change alters when and where a protein is produced, thereby enabling the interpretation of genetic variants in the other 99% of the genome. We aim to evaluate nine cases that have been enrolled through the Manton Center using this approach to help identify any genetic alterations underlying their disease.

 

This page was last updated January 26, 2021.