Poster sessions are an opportunity for researchers to showcase their work in Basic and Clinical Sciences to an audience of NF researchers. A panel of judges select the top posters, and these investigators are invited to present their work in front of the full conference.
Below are the top posters at the 2021 NF Conference in Clinical and Basic Sciences.
CLINICAL SCIENCE
1) Kimberly Marrs, Graduate Student, California State University – Sacramento
Survey of Communication, Swallowing, and Hearing of Individuals with NF1: A Pilot Project
2) Edgar Creus, IDIBELL, Spain
A high-throughput screening identifies the combination of MK-1775 and Doxorubicin as a new therapeutic approach for MPNST
3) Priya Chan, MD, Fellow, Children's Hospital Colorado
Post-operative use of MEK inhibitors to prevent rebound growth following partial resection of plexiform neurofibromas
BASIC SCIENCE
1) Jennifer Patritti Cram, PhD Student, Cincinnati Children's Hospital
P2RY14 modulates Schwann cell precursor self-renewal and tumor initiation in mouse model of neurofibromatosis type 1.
2) Myriam Mansour, PhdD Student, INSERM, France
Exploring mechanisms driving initiation and progression of plexiform neurofibromas from Prss56Cre, Nf1fl/fl mouse model
3) Garrett Draper, PhD Student, University of Minnesota
Induced pluripotent stem cell derived Schwann cells harboring MPNST-associated mutations fail to escape senescence in vitro
Keep reading for the complete abstracts.
CLINICAL SCIENCE
1) Kimberly Marrs, Graduate Student, California State University – Sacramento
Survey of Communication, Swallowing, and Hearing of Individuals with NF1: A Pilot Project
Communication, swallowing, and hearing concerns are documented in individuals with neurofibromatosis type 1 (NF1; Thompson et al., 2013). While direct assessment methods such as standardized tests of speech or language are typically used to evaluate an individual’s communication skills, these measures are limited in that they frequently do not consider individuals’ perceptions of their own communication functioning and communication related quality of life. Presently, there are few patient reported outcome measures (PROMs) used to assess self-reported communication functioning (Cosyns et al., 2010), swallowing, or communication related quality of life factors in individuals with NF1. Disease specific PROMs are needed to assess clinical benefit of an intervention above and beyond improvements captured through direct assessment. The purpose of this study was to develop a PROM to assess self-reported communication functioning, swallowing, and communication related quality of life factors for individuals with NF1.
2) Edgar Creus, IDIBELL, Spain
A high-throughput screening identifies the combination of MK-1775 and Doxorubicin as a new therapeutic approach for MPNST
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue sarcomas that are associated with Neurofibromatosis type 1 (NF1), as half of the cases are diagnosed in NF1 patients. Currently, the best therapy for MPNSTs is complete surgical resection, but often it is not possible due to location or metastases. Chemotherapy or radiotherapy has not been proven effective and new therapies are needed to be tested as potential treatments. For many cancers, drug combinations are emerging as the therapeutic strategy of choice to overcome treatment failure. Herein, we aim to test eleven potential synergistic combinations of compounds selected from a high-throughput screening of almost 2000 compounds performed in the NIH-NCATS to choose the best candidates as potential novel treatments for MPNST.
3) Priya Chan, MD, Fellow, Children's Hospital Colorado
Post-operative use of MEK inhibitors to prevent rebound growth following partial resection of plexiform neurofibromas
Plexiform neurofibromas (PNs) are benign peripheral nerve sheath tumors that occur in patients with neurofibromatosis type I (NF1). While they are benign in nature, these tumors can cause significant morbidity leading to functional impairment, pain, and disfigurement. Management of PNs is challenging. Complete surgical resection is often not possible due to tumor growth along vital structures, and rebound growth is frequently experienced with partially resected PNs.1 More recently, the mitogen-activated protein kinase (MAPK) pathway has been implicated in the growth of PNs, and the use of MAPK enzyme (MEK1/2) inhibitors has been shown to be an effective therapy in the treatment of PNs.
BASIC SCIENCE
1) Jennifer Patritti Cram, PhD Student, Cincinnati Children's Hospital
P2RY14 modulates Schwann cell precursor self-renewal and tumor initiation in mouse model of neurofibromatosis type 1.
Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by tumors in peripheral nerves called neurofibromas. We found that the purinergic receptor P2RY14 is expressed in human and mouse neurofibroma Schwann cell precursor-like cells (SCPs) and in Schwann cells (SCs). Neurofibroma P2RY14+ SCP-like cells were enriched in cells with the potential to self-renew. Conversely, SCP self-renewal was blocked by pharmacologic or genetic targeting of P2RY14 in mouse Nf1 mutants. Downstream of P2RY14, Gi-mediated cAMP signaling contributed to these effects. In vivo, P2RY14 loss delayed neurofibroma initiation, normalized nerve architecture, rescued the reduced cAMP characteristic of neurofibromas and normalized neurofibroma cell proliferation. Modulating cAMP also reduced cell proliferation. Thus, the purinergic receptor P2RY14 regulates SCP self-renewal and neurofibroma initiation, and to a lesser extent, contributes to later stages of tumorigenesis. These gain and loss of function experiments suggest roles for P2RY14 signaling in peripheral nerve that are perturbed by loss of the NF1 tumor suppressor.
2) Myriam Mansour, PhdD Student, INSERM, France
Exploring mechanisms driving initiation and progression of plexiform neurofibromas from Prss56Cre, Nf1fl/fl mouse model
Patients with Neurofibromatosis type 1 (NF1) develop benign nerve sheath tumors called plexiform (pNFs) and cutaneous neurofibromas (cNFs). While common biallelic loss of NF1 in Schwann cell lineage is at the origin of both type of tumors, pNFs substantially differ from cNFs in their number, mode of growth and capacity to progress into malignancy. Seminal progresses were made during the last decade in characterizing pNFs and deciphering mechanisms governing their malignant transformation. However, the cues and pathways driving progression of hyperplastic nerves (HN) into fully blown pNFs remain largely enigmatic. Our group has developed a new genetically engineered mouse (GEM) model of NF1 faithfully recapitulating development of plexiform and cutaneous NFs including malignant progression of the former. Interestingly, while in this model HN were observed in the hypodermis from young mutant males and slowly progress into pNFs, this progression is accelerated in the same age mutants kept together and having numerous bites pointing to skin trauma as potentially key factor promoting their development.
3) Garrett Draper, PhD Student, University of Minnesota
Induced pluripotent stem cell derived Schwann cells harboring MPNST-associated mutations fail to escape senescence in vitro
The genetic tumor predisposition syndrome Neurofibromatosis type 1 (NF1) results from the inheritance of a mutant copy of NF1, a RAS-GAP tumor suppressor gene. Subsequent loss of the remaining wild-type NF1 allele in Schwann cells or Schwann cell precursors of the peripheral nervous system leads to complete functional loss of the encoded protein, neurofibromin. Schwann cells lacking neurofibromin exhibit hyperactive RAS signaling, increased cell proliferation, and contribute to the formation benign plexiform neurofibromas (PNFs). Through additional mutations in tumor suppressor genes CDKN2A/CDKN2B, these PNFs may escape senescence and progress to atypical neurofibromatous neoplasms of uncertain biological potential (ANNUBP). Furthermore, loss of function mutations in the histone modifying Polycomb Repressive Complex 2 (PRC2) have been strongly implicated in the progression of ANNUBPs to lethal malignant peripheral nerve sheath tumors (MPNSTs). Although these and other genetic alterations have been associated with MPNST formation, their temporal dependence during Schwann cell development and contribution to malignant transformation using a human cell model has not been studied.
