BA, Augustana University, Sioux Falls, SD

Mentor: Dawn Quelle, PhD

4th Year Medical Student

 Comprehensive Exam: Transformation of PNFs to MPNSTs through cooperation of INK4a/ARF loss with RABL6A overexpression

Malignant peripheral nerve sheath tumors (MPNSTs) are rare and deadly sarcomas with few treatment options. Patients with a heritable disorder called Neurofibromatosis type I spontaneously develop benign tumors called plexiform neurofibromas (PNFs) that transform into MPNSTs ~15% of the time. MPNSTs are genetically characterized by loss of NF1 and >80% of the tumors have alterations in the INK4a/ARF/INK4b tumor suppressor locus (commonly known as CDKN2A/CDKN2B). In addition, a GTPase called RABL6A is overexpressed in the majority of human MPNSTs. My project seeks to understand how these alterations cooperate to form malignant tumors by modeling transformation of PNFs into MPNSTs through CRISPR-Cas9 gene editing of INK4a, ARF, and/or INK4b paired with overexpression of RABL6A and other proteins of interest.  

Publications:

1. Voigt E, Quelle DE. FOXM1, MEK, and CDK4/6: New Targets for Malignant Peripheral Nerve Sheath Tumor Therapy. Int J Mol Sci. 2023;24(17)

2. Kohlmeyer JL, Lingo JJ, Kaemmer CA, Scherer A, Warrier A, Voigt E, et al. CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression. Clinical cancer research : an official journal of the American Association for Cancer Research. 2023

3. Koppenhafer SL, Goss KL, Voigt E, Croushore E, Terry WW, Ostergaard J, et al. Inhibitor of DNA binding 2 (ID2) regulates the expression of developmental genes and tumorigenesis in ewing sarcoma. Oncogene. 2022;41(20):2873-84

4. Kohlmeyer JL, Kaemmer CA, Lingo JJ, Voigt E, Leidinger MR, McGivney GR, et al. Oncogenic RABL6A promotes NF1-associated MPNST progression in vivo. Neurooncol Adv. 2022;4(1):vdac047

ORCiD: 0000-0002-3013-2130

Cancer Biology PhD Program