Dr. Hector Peinado Selgas of Centro Nacional de Investigaciones Oncologicas (CNIO)

Dr. Hector Peinado Selgas of Centro Nacional de Investigaciones Oncologicas (CNIO) has been interested in the field of NF research since 2012.  In this project, Dr. Peinado Selgas proposes to examine the novel concept that circulating exosomes from NF1 patients could play a role in NF1-driven tumor progression and can be used as a biomarker to predict disease outcomes.  He will also investigate whether blocking specific exosome cargo could potentially be a novel therapy to inhibit tumor progression. This project will provide the first insights into the role of tumor-secreted exosomes in plexiform neurofibroma progression and malignant peripheral nerve-sheath tumor transformation, and could lead to a new therapy to target tumors in NF1 patients.

Dr. Harini Sundararaghavan of Wayne State University

Dr. Harini Sundararaghavan of Wayne State University is a biomedical engineer who has previously focused on nervous system repair following injury.  After collaborating with veteran NF1 researcher Dr. Raymond Mattingly, Dr. Sundararaghavan became interested in leveraging her work in materials development to optimize organotypic models of cancer to develop a system that includes several cell types to test clinically relevant pharmacological therapies for NF1.  Her project proposes to provide the first in vitro organotypic models of NF1 plexiform neurofibromas.  These co-culture systems will more accurately model the disease to allow for preclinical drug screening at a much higher throughput than is available in animal models.

Dr. Lei Xu of Massachusetts
General Hospital

Dr. Lei Xu of Massachusetts General Hospital has only recently started working in the NF2 field, and she has already made advances in the understanding of vestibular schwannomas (VS).  Those advances include developing better animal models to study VS.  Using these models, Dr. Xu was able to show that vasculature in schwannomas is abnormal, and that anti-VEGF treatment in these models leads to a short-term normalization of tumor vasculature.  She also has data indicating that immune checkpoint molecules are present in schwannomas.  With her NIA, she proposes to test whether combined use of anti-VEGF treatment and immune checkpoint inhibitors will provide a more effective therapy for VS in NF2 patients.

Dr. Marc Wolman of the University of Wisconsin at Madison

Dr. Marc Wolman of the University of Wisconsin at Madison started working in the NF1 field in 2011 via a “side project,” but has since found that NF research perfectly fulfills his research interests.  With this award, using a zebrafish NF1 mutant that exhibits phenotypes of NF1, he proposes to build upon the recent studies indicating that cAMP signaling plays a role in NF1 cognitive impairment, specifically with regard to attention-based learning.  Dr. Wolman also plans to screen libraries of compounds with known molecular targets to identify molecular substrates that can be targeted to reduce the attention-based learning disability in NF1, with the hope that since the compound libraries contain many Food and Drug Administration-approved drugs, potential treatments could be moved quickly to clinical trials.

Dr. John Albeck of University of California at Davis

Dr. John Albeck of University of California at Davis has been primarily focused on NF1 and RASopathies and developing unique high-resolution tools to study the Ras signaling pathway for the past two years.  Recent studies have shown that kinetic parameters (i.e., intensity, duration, etc.) of ERK and Akt signaling are important to downstream effects of these pathways.  Dr. Albeck plans to use his NIA to study different classes of NF1 mutations and the resulting changes in kinetic parameters of downstream Ras signaling, as well as the effects of inhibitors on these kinetic parameters.  He hopes to use the data generated from this project for therapeutic benefit by identifying the best inhibition strategies to attenuate downstream effects of different NF1 mutations, leading to a personalized medicine approach to treating NF1.