DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

The NFRP Supports the Future of NF Research with Several New Investigator Awards

Posted November 3, 2020

The Neurofibromatosis Research Program (NFRP) utilizes the New Investigator Award (NIA) to introduce the next generation of investigators and their ideas to the Neurofibromatosis (NF) research community. This award mechanism aims to support the continued development of promising new independent investigators or established investigators transitioning from other career fields who can bring new techniques or expertise into the field of NF research. The first NFRP NIA was awarded in 1999; since then, 326 NIA applications have been received, of which 73 have been recommended for funding. In fiscal year 2019, seven NIAs were awarded. The research planned by these investigators addresses different NF research topic areas of interest, and all NIA researchers are bringing novel concepts to the NF research community.

Richa Saxena, Ph.D., Massachusetts General Hospital
Dr. Richa Saxena

Dr. Richa Saxena of Massachusetts General Hospital is studying sleep and circadian patterns and disturbances in patients with NF1. To study sleep, they will utilize actigraphy, overnight home sleep, electroencephalogram (EEG), melatonin assays, and gene expression analyses. Dr. Saxena aims to determine how sleep disturbance and poor sleep quality occur in individuals with NF1. Information on specific aspects of sleep will enable targeted interventions to improve the quality of life for NF1 patients.

Kunal Rai, Ph.D., MD Anderson Cancer Center
Dr. Kunal Rai

Dr. Kunal Rai of MD Anderson Cancer Center is studying the RNA processing deficits mediated by RNA exosome complex in the PRC2-mutant NF1-associated malignant peripheral nerve sheath tumor (MPNST) cells. Dr. Rai will identify the status of non-coding RNA-species that are substrates for RNA-exosomes specifically in PRC2-mutant MPNSTs and assess the involvement of mistargeted EZH2 and SKIV2L2 in this process. The findings from this study may identify the RNA-exosome as a target for therapy in PRC2-mutant MPNSTs.

Thomas De Raedt, Ph.D., Children's Hospital of Philadelphia
Dr. Thomas De Raedt

Dr. Thomas De Raedt of Children's Hospital of Philadelphia is studying how ATRX loss drives NF1-related high-grade Glioma (HGG) formation by modulating PRC2 function. Dr. De Raedt will evaluate whether NF1 HGG are sensitive to MEK and BRD4 inhibitor combination immunotherapies and determine whether ATRX loss confers a sensitivity to histone demethylase inhibitors. This project will potentially inform future clinical trials for NF1 HGG.

 Matthew Kayser, M.D., Ph.D., University of Pennsylvania
Dr. Matthew Kayser

Dr. Matthew Kayser of the University of Pennsylvania is studying the mechanism through which NF1 regulates chemosensory neuronal function. Dr. Kayser will determine how sensory dysregulation in NF1 alters neural coding of social experience in the brain and identify small molecule modifiers of NF1-associated social dysregulation, leading to potential treatments.

Santhi Ganesh, M.D., University of Michigan
Dr. Santhi Ganesh

Dr. Santhi Ganesh of the University of Michigan is studying the etiology of pediatric arterial dysplasia and renovascular hypertension (HTN), using genomic approaches to identify genetic alterations. Dr. Ganesh will perform sequencing analysis of NF-1 arteriopathy using peripheral blood DNA to identify de novo mutations and other pathogenic variants and modifier genes. These studies will be complemented by arterial tissue studies. An improved understanding of the mechanisms of NF-1 arteriopathy will ultimately lead to novel treatments that prevent arterial remodeling and HTN in pediatric patients.

Angela Hirbe, M.D., Ph.D., Washington University in St. Louis
Dr. Angela Hirbe

Dr. Angela Hirbe of Washington University in St. Louis is studying whether TYK2 promotes MPNST growth and assessing the utility of TYK2 expression as a potential prognostic marker for MPNST progression. Dr. Hirbe aims to determine whether TYK2 expression levels are associated with poor overall survival and response to therapy, as well as whether TYK2 expression can distinguish atypical neurofibromas from MPNST. Dr. Hirbe will also aim to define the precise molecular mechanism underlying TYK2 regulation of MPNSTs and explore the utility of TYK2 inhibitors as a potential therapy for MPNST.

Matthew Hocking, Ph.D., Children's Hospital of Philadelphia
Dr. Matthew Hocking

Dr. Matthew Hocking of Children's Hospital of Philadelphia is studying the cognitive and affective function (CAF) abilities of youth with NF1 and establishing associations between CAF abilities and measures of social adjustment. Dr. Hocking will aim to describe the neurobiological mechanisms underlying the CAF abilities of youth with NF1 using neuroimaging. Understanding the basis of the social dysfunction seen in youth with NF1 will pave the way for screening and intervention efforts aimed at improving quality of life.

Links:

Public and Technical Abstracts: Longitudinal, Objective Measurement and Analysis of Sleep-Wake Patterns in NF1 Patients 

Public and Technical Abstracts: Role of RNA-Exosome in PRC2- and NF1-Mutant Malignant Peripheral Nerve Sheath Tumors 

Public and Technical Abstracts: Elucidating the Role of ATRX in NF1-Associated High-Grade Glioma Formation 

Public and Technical Abstracts: Molecular and Neural Mechanisms of Social Behavioral Differences in NF1 

Public and Technical Abstracts: Genetic Mechanisms of Neurofibromatosis-Related Arteriopathy and Renovascular Hypertension 

Public and Technical Abstracts: TYK2 as a Biomarker and Therapeutic Target for NF1-Associated Malignant Peripheral Nerve Sheath Tumors 

Public and Technical Abstracts: Mechanisms of Social Deficits in Youth with Neurofibromatosis Type 1

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Last updated Friday, December 13, 2024