Neurofibromatosis is a very common genetic disorder affecting 1 out of 3,000 children and adults. NF1 patients can develop brain and nerve tumors that can compromise brain and nerve structure and function. We aim to pursue cancer research, and primarily study nerve tumors, with the goal of improving the quality of life of >110,000 people in the U.S., and many more worldwide.
My research interests include glial cell biology, intracellular signaling, preclinical therapeutics, and peripheral nerve tumorigenesis. My laboratory team and I share the goal of finding innovative treatments for neurofibromatosis by utilizing our knowledge of developmental biology together and levels of ribonucleic acid (RNA) and proteins in neurofibroma tumor and immune cell types as guides for drug selection and testing.
Some of the notable discoveries my team and I have made in our lab include: 1) developing and producing transcriptome data for investigating NF1 cells and nerve tumors and 2) pioneering the use of mitogen-activated protein kinase (MEK) inhibitors in a new and original preclinical model of the peripheral nerve tumor. This research led clinicians to pursue clinical trials, and in 2020, the Food and Drug Administration (FDA) granted approval for use of MEK inhibitors as a therapy for plexiform neurofibromas.
I also recruit and mentor neuro-oncology and rasopathy faculty at the Cincinnati Children’s Hospital Medical Center, and mentor students and postdoctoral fellows in my laboratory.
Throughout my career, I received awards, including:
I joined the Cincinnati Children’s Hospital Medical Center team in 2006. I now have more than 30 years of experience in Schwann cell biology and cancer research. My research has been consistently funded by the National Institutes of Health, the Department of Defense Program on Neurofibromatosis and other agencies. My work has been published in numerous journals, including Cancer Cell, Cell Reports, Scientific Reports, Cancer Research, PNAS and Clinical Cancer Research.
PhD: Indiana University, 1982.
BA: Brown University, 1975.
Fellowship: Washington University St. Louis, 1982-1987.
Preclinical testing in neurofibromatosis
Genetic mutations in tumor suppressor genes; development and tumorigenesis of the nervous system; peripheral NF1, NF2
Experimental Hematology and Cancer Biology, Cancer and Blood Diseases
Multiple Nf1 Schwann cell populations reprogram the plexiform neurofibroma tumor microenvironment. JCI insight. 2022; 7.
The Need for New Treatments Targeting MPNST: The Potential of Strategies Combining MEK Inhibitors with Antiangiogenic Agents. Clinical Cancer Research. 2022; 28:3185-3195.
P2RY14 cAMP signaling regulates Schwann cell precursor self-renewal, proliferation, and nerve tumor initiation in a mouse model of neurofibromatosis. eLife. 2022; 11.
Cdkn2a Loss in a Model of Neurofibroma Demonstrates Stepwise Tumor Progression to Atypical Neurofibroma and MPNST. Cancer Research. 2021; 80:4720-4730.
Cdc42 activity in Sertoli cells is essential for maintenance of spermatogenesis. Cell Reports. 2021; 37.
Purinergic signaling in peripheral nervous system glial cells. GLIA. 2021; 69:1837-1851.
WNT5A inhibition alters the malignant peripheral nerve sheath tumor microenvironment and enhances tumor growth. Oncogene. 2021; 40:4229-4241.
Neurofibromatosis in the Era of Precision Medicine: Development of MEK Inhibitors and Recent Successes with Selumetinib. Current Oncology Reports. 2021; 23.
Transposon Mutagenesis-Guided CRISPR/Cas9 Screening Strongly Implicates Dysregulation of Hippo/YAP Signaling in Malignant Peripheral Nerve Sheath Tumor Development. Cancers. 2021; 13.
NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas. Journal of Clinical Oncology. 2021; 39:797-806.