Francis S. Collins Scholars Program

The Francis S. Collins Scholars Program in Neurofibromatosis Clinical and Translational Research is building a community of exceptional clinician scientists who will lead neurofibromatosis type 1 (NF1) research and clinical care.

The Scholars Program is named in honor of Dr. Francis S. Collins, who led the team that discovered the NF1 gene in 1990. In addition to this work, Dr. Collins has been at the forefront of advancing translational science in his roles as Director of the National Institutes of Health (NIH) and former Director of the National Human Genome Research Institute. His leadership helped to establish the National Center for Advancing Translational Sciences (NCATS) and Brain Research through Advancing Innovative Neurotechnologies (BRAIN).

By providing the “Collins Scholars” with critical support and training in the management of NF1 and the conduct of rigorous clinical translational research, the program aims to revolutionize the field of NF1 and improve treatment options for patients now and in the future.

Explicitly designed to attract talent of the highest order to the field of NF1 and to foster life-long commitment to this syndrome, the program provides scholars with:

• 75-100% salary support for 2-3 years
• Training in the care of NF1 patients
• Tuition support and formal training in clinical translational science
• Participation in collaborative translational research programs with government, academic and industry partners
• Travel costs for scientific meetings
• Mentor and research stipends

Current  NTAP-funded Francis S. Collins Scholar projects:

Neurofibromatosis Type 1 Dermal Neurofibroma Longitudinal Natural History Study and Selumetinib Clinical Trial

Ashley Cannon, Ph.D., M.S., University of Alabama

The overall goal of Dr. Cannon’s project is to complete a longitudinal natural history study of dermal neurofibromas to enhance current knowledge of dermal neurofibroma development as well as improve the design, implementation, and interpretation of clinical trials targeting DNs. To address the clinical trial facet of this project, a trial using the MEK1/2 inhibitor selumetinib will be piloted. Dr. Cannon will also evaluate the quality of life impact of dermal neurofibromas before and during Selumetinib treatment. For both facets of this study, she and her team will examine genomic alterations that correlate with DN development and selumetinib response.

NarrativeRead about the project’s background, goals, specific aims, methods, preliminary results, and impact (auspices of Dr. Ashley Cannon,

Development of a novel treatment approach to Neurofibromatosis Type 1-related MPNST using genetically engineered Clostridium novyi-NT

Verena Staedtke, M.D., Ph.D. Johns Hopkins University

The overall goal of Dr. Staedtke’s project is to explore C. novyi-NT as a novel therapeutic for NF1-associated MPNSTs and to gather preclinical evidence substantiating clinical trial for for C. novyi-NT therapy in NF1 patients with MPNSTs.

Narrative: Read about the project’s background, goals, specific aims, preliminary results, and impact (auspices of Dr. Verena Staedtke,

Publication 1: Roberts NJ, Zhang L, Janku F, Collins A, Bai RY, Staedtke V, et al. Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses. Sci Transl Med 6 (249), 249ra111 (2014)

Publication 2Staedtke V, Bai RY, Laterra JJ. Investigational new drugs for brain cancer. Expert Opin Investig Drugs. 2016 Aug;25(8):937-56. doi: 10.1080/13543784.2016.1182497. (Review)

Publication 3Staedtke V, Robert NJ, Bai RY, Zhou S. Clostridium novyi-NT in cancer therapy. Journal for Genes and Disease: Volume 3, Issue 2, June 2016, Pages 144–152 (Review)

Publication 4: Bai RY, Staedtke V, Xuwei X, Riggins GJ. Prevention of tumor seeding during needle biopsy by chemotherapeutic-releasing gelatin sticks. Oncotarget. 2017 Feb; 8(16): 25955-25962.

Publication 5:  Staedtke V, Bai RY, Blakeley JO. Cancer of the peripheral nerve in neurofibromatosis Type 1. (Review). Neurotherapeutics. 2017, 14: 298-306.

The Role of MEK-inhibitors for the Prevention and Treatment of Optic Pathway Gliomas in an NF1 Deficient Mouse Model

Miriam Bornhorst, M.D., Children’s National

Proving that treatment with MEKi in established tumors can provide therapeutic benefits, delaying expansion of the tumor by either decreasing or delaying immune cell response, axonal injury, and RGC loss. The goals of Dr. Bornhorst’s study are to 1) identify a potential developmental time window when low dose MEKi can be used to prevent OPG formation all together and 2) provide critical information about optic nerve changes that are responsible for vision loss during OPG formation, and how MEKi can be used to improve visual deficits.

Narrative: Read about the project’s background, goals, specific aims, highlights, and preliminary results (auspices of Dr. Miriam Bornhorst,

Publication 1: Bornhorst M, Hwang EI. Experimental Therapeutic Trial Design for Pediatric Brain Tumors. J Child Neurol. 2016 Oct;31(12):1421-32.

Publication 2: Packer RJ, Pfister S, Bouffet E, Avery R, Bandopadhayay P, Bornhorst M, Bowers DC, Ellison D, Fangusaro J, Foreman N, Fouladi M, Gajjar A, Haas-Kogan D, Hawkins C, Ho CY, Hwang E, Jabado N, Kilburn LB, Lassaletta A, Ligon KL, Massimino M, Meeteren SV, Mueller S, Nicolaides T, Perilongo G, Tabori U, Vezina G, Warren K, Witt O, Zhu Y, Jones DT, Kieran M. Pediatric low-grade gliomas: implications of the biologic era. Neuro Oncol. 2016 Sep 28

Imaging Biomarkers of Neurofibromatosis Type 1-Associated Optic Pathway Glioma

Peter de Blank, M.D., Cincinnati Children’s Hospital Medical Center

The main goals of the project is the interrogation of 2 two promising advanced magnetic resonance techniques, DTI and MRF, investigating tissue microstructure in OPG

Narrative: Read about the project’s background, goals, specific aims, and preliminary results (auspices of Dr. Peter de Blank,

Publication 1: de Blank PM, Fisher MJ, Lu L, Leisenring WM, Ness KK, Sklar CA, Stovall M, Vukadinovich C, Robison LL, Armstrong GT, Krull KR. (2016). Impact of Vision Loss Among Survivors of Childhood Central Nervous System Astroglial Tumors. Cancer 2016 Mar 1;122(5):730-9.

Publication 2: de Blank P, Berman JI, Fisher MJ. (2016). Systemic Chemotherapy and White Matter Integrity in Tracts Associated with Cognition Among Children with Neurofibromatosis Type 1. Pediatric Blood & Cancer 2016 May; 63(5):818-24

Publication 3: de Blank P, Ellika S, Kader M, Fisher MJ. Advanced Imaging in Optic Pathway Gliomas. In press (Journal of Pediatric Neuroradiology)

Targeting the mechanisms underlying cutaneous neurofibroma formation in NF1: a clinical translational approach

Matthew R. Steensma, M.D., Spectrum Health

To mitigate the morbidity and disfigurement attributable to CNFs arising in NF1, in this project, Steensma’s objective is to improve health and quality of life (QOL) by targeting essential mechanisms of CNF initiation and progression. In doing so, we will define a molecular pathogenesis specific to CNFs that encompasses existing knowledge regarding CNF cell-of-origin, as well as new knowledge regarding the role of cellular intrinsic factors such as DNA damage repair mechanisms, secondary mutations, epigenetic regulation of gene expression, and aberrant oncogene activation; extrinsic factors such as autocrine/paracrine feedback loops; and environmental factors such as ultraviolet radiation..

NarrativeRead about the project’s background, goals, aims, methods, and impact (auspices of Dr. Matthew Steenma’s,

Current Francis S. Collins Scholars:

Dr. Ashley Cannon, Ph.D., M.S., the 2016-selected scholar of the Francis S. Collins Program in Neurofibromatosis Clinical and Translational Research.

DSC_0190, for web- Staedtke  DSC_0188, for web- Bornhorst

Dr. Collins honoring Dr. Verena Staedtke, M.D. (left) and Dr. Miriam Bornhorst, M.D. (right), the two 2015-selected scholars of the Francis S. Collins Program

AEB_9534     AEB_9524

Dr. Collins honoring Dr. Matthew R. Steensma, M.D. (left) and Dr. Peter de Blank, M.D., M.S.C.E, (right), the two 2014-selected scholars of the Francis S. Collins Program