Posted April 5, 2019

Renyuan Bai, Ph.D., Johns Hopkins University
Rebecca Dodd, Ph.D., University of Iowa
Wei Li, Ph.D., Pennsylvania State University, Hershey Medical Center

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.  Since the first NFRP NIA in 1999, there have been 326 NIA applications received; of those, 73 have been recommended for funding.  The goal of this award mechanism is 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.  In fiscal year 2017, three NIAs were awarded.  The research planned by these investigators addresses different NF research topic areas of interest, and all three NIA researchers are bringing novel concepts to the NF research community.

Dr. Renyuan Bai, while at the Technical University of Munich, focused on the nucleophosmin-anaplastic lymphoma kinase oncoprotein in leukemia and lymphoma.  During this time, he identified and characterized several key cellular pathways, which assisted in the development of therapeutics.  Later, when he took a lead position in protein engineering at Roche Vitamins, Ltd./DSM, he successfully engineered mevalonate kinase.  Dr. Bai took his knowledge and skills to Johns Hopkins University’s neurosurgical department, where he focused on therapies for neurological tumors and began to work with Dr. Verena Staedtke, the Director of Pediatric Neurofibromatosis.  Through this collaboration, Dr. Bai’s interest in NF1-related tumors began, specifically in gene replacement therapies for the NF1 driver mutation.  Dr. Bai and Dr. Staedtke propose to optimize a virus-based gene therapy for use in NF1-caused malignant peripheral nerve sheath tumors (MPNSTs).  Gene therapy is presently an unexplored area of treatment for MPNSTs.  This preclinical research, which includes developing an engineered adeno-associated virus (AAV) vector and a humanized mouse model with MPNST and immunity traits, could lead to future clinical trials to move this treatment to the clinic. If successful, this work will be the first treatment for NF1 patients that corrects the molecular cause of MPNSTs.

Dr. Rebecca Dodd developed genetically engineered mouse models at Duke University to study multiple different variables concerning NF1-associated MPNSTs.  The models she developed are used in multiple laboratories, and for her work on these NF1-deficient models, she received the Young Investigator Fellowship award from the Children’s Tumor Foundation (CTF) in 2012.  Dr. Dodd is currently an Assistant Professor at the University of Iowa, where she continues to design mouse models to improve oncology research and address critical questions in NF1 tumor biology.  With the NIA, Dr. Dodd proposes to gain a better understanding of the cellular biology in MPNSTs by using CRISPR-Cas9 technology to model tumor biology in mice, specifically the role of mast cells and monocytes.  To conduct this research, Dr. Dodd plans to collaborate with the Sarcoma Multidisciplinary Oncology Group at the University of Iowa, directed by Drs. Benjamin Miller and Munir Tanas of the Holden Comprehensive Cancer Center.  If successful, this research will demonstrate that inhibiting specific immune cells could slow the growth of MPNSTs, and therefore, validating new cellular targets for treatment, such as myeloid cells or their cytokines.

Dr. Wei Li conducted his post-doctoral research with Dr. Filippo Giancotti at Memorial Sloan Kettering Cancer Center and focused on deciphering the function and regulation of the Merlin/NF2-Hippo pathway.  For this research, he used mammalian cell culture and mouse tumor models, furthering his graduate work at Albert Einstein College of Medicine where he used Drosophila to study cell biology relevant to tumorigenesis.  Dr. Li’s research in both areas led to publications in Cell, and in 2009, he received the Young Investigator Award from the CTF.  Currently, Dr. Li is an Assistant Professor at Pennsylvania State University’s Hershey Medical Center in the Department of Pediatrics, where he plans to continue developing his expertise in NF2 and calcium signaling in cancer.  With the NIA, he proposes to investigate the recently discovered link between calcium and Merlin post-translational modification by the protein, ubiquitin.  Examining the modification of Merlin, a multifunctional protein, could demonstrate the mechanism of Hippo pathway regulation and tumor suppression.  If successful, this study will open avenues for the development of more effective therapies by providing a better understanding how Merlin is dysfunctional in NF2 individuals.

Links:

Abstracts for Dr. Bai

Public and Technical Abstracts:  Gene Replacement Therapy for Neurofibromatosis 1-Related Tumors with AAV Virus

Abstracts for Dr. Dodd

Public and Technical Abstracts:  Mechanisms of NF1+/- Myeloid Cell Function in MPNSTs

Abstracts for Dr. Li

Public and Technical Abstracts:  Identification and Characterization of a Novel Posttranslational Modification of Merlin in Tumor Suppression

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