Jordan Kohlmeyer

Mentor: Dawn E. Quelle, PhD

Year Entered Into Program: 2016

Terminal Degree(s) Received and Year: PhD 2021


Molecular Medicine

Research Description

Targeting RABL6A-regulated pathways to combat MPNST pathogenesis

Malignant peripheral nerve sheath tumors (MPNSTs) are deadly sarcomas that lack effective therapies. Greater insight into MPNST pathogenesis is needed to develop new, more targeted treatments. In most MPNSTs, the retinoblastoma (RB1) tumor suppressor is disabled by hyperactivation of cyclin dependent kinases (CDKs), commonly cyclin D-CDK4/6 and cyclin E-CDK2. We recently showed RABL6A, an oncogenic GTPase, is markedly upregulated in MPNSTs and promotes their survival and proliferation by negatively regulating the RB1 pathway. Pharmacological inhibition of CDK4/6 effectively reactivated RB1 and suppressed growth of orthotopic MPNSTs; however, sustained therapy led to drug resistance. Notably, RABL6A controls many cancer pathways besides CDK-RB1 including MEK-ERK, AKT-mTOR, Myc, MDM2-p53 and receptor tyrosine kinase (RTK) signaling (e.g., VEGFR). Therefore, the goal of my work is to use our knowledge of RABL6A in MPNSTs to develop meaningful, effective combination therapy that may translate to other subtypes of sarcoma.

Patient tumor analyses uncovered druggable, activated pathways regulated by RABL6A in MPNSTs. That information guided rational drug combination studies, through which we identified new combination therapies that may be highly effective against MPNSTs. Current studies are focused on pharmacologically targeting the CDK-RB1 (CDK4/6 inhibitor, palbociclib) and MEK-ERK (MEK inhibitor, mirdametinib) pathways in MPNSTs. Preliminary studies in vitro and in vivo demonstrate high synergy between these two drugs to prevent MPNST growth and survival. Through collaboration with other researchers at UI (Ben Darbro, Munir Tanas, Rebecca Dodd, Eric Taylor, and Varun Monga), we aim to understand how these two drugs are altering MPNST growth, immune response, and metabolomic signature to cause tumor regression and extended animal survival. Overall, we aim to fully evaluate the effectiveness of this drug combination in MPNSTs and hope to translate its use to other sarcoma subtypes to improve patient treatments.


  • Top Presentation Award, Holden Comprehensive Cancer Center Retreat, University of Iowa, 2020
  • Sarcoma Multidisciplinary Oncology Group Pilot Award, University of Iowa, 2020
  • Poster Presentation Award, Children’s Tumor Foundation NF International Conference, 2019
  • Children's Tumor Foundation Young Investigator Award, 2019-2021
  • Graduate Student Senate and Graduate College Travel Award, 2019
  • Dare to Discover Campaign, University of Iowa, 2019
  • Ranbir K Bhatnagar Scholar Award, University of Iowa, 2018
  • Pharmacological and Pharmaceutical Sciences Research Retreat Oral Presentation Award, 2018
  • Fellowship appointment on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2017-2019
  • Graduate College Iowa Recruitment Fellowship, 2016


  1. Kohlmeyer JL, Kaemmer CA., Shaikamjad, U., Gourronc, FA., Klingelhutz AJ., and Quelle DE.: RABL6A Regulates Schwann Cell Senescence in an RB1-Dependent Manner.  Int. J Mol Sci 2021, 22(10), 5367;
  2. Kohlmeyer JL, Gordon DJ, Tanas MR, Monga V, Dodd RD, and Quelle, DE.: CDKs in Sarcoma: Mediators of Disease and Emerging Therapeutic Targets. International Journal of Molecular Sciences, 21(8):3018, 2020.  PMID: 32344731; PMCID: PMC7215455
  3. Kohlmeyer JL,  Kaemmer CA, Pulliam C, Maharjan CK,  Moreno Samayoa A, Major HJ,  Cornick KE,  Knepper-Adrian V,  Khanna R, Sieren JC,  Leidinger M, Meyerholz DK, Zamba KD,  Weimer J,  Dodd RD, Darbro B, Tanas MR, and Quelle DE.:  RABL6A is an essential driver of MPNSTs that negatively regulates the RB1 pathway and sensitizes tumor cells to CDK4/6 inhibitors. Clinical Cancer Research, 26(12):2997-3011, 2020.  PMID: 32086342; PMCID: PMC7299809
  4. Umesalma S, Kaemmer CA, Kohlmeyer JL, Letney B, Schab AM, Reilly JA, Sheehy RM, Hagen J, Tiwari N, Zhan F, Leidinger MR, O'Dorisio TM, Dillon J, Merrill RA, Meyerholz DK, Perl AL, Brown BJ, Braun TA, Scott AT, Ginader T, Taghiyev AF, Zamba GK, Howe JR, Strack S, Bellizzi AM, Narla G, Darbro BW, Quelle FW, Quelle DE.:  RABL6A inhibits tumor-suppressive PP2A/AKT signaling to drive pancreatic neuroendocrine tumor growth. J Clin Invest 129(4):1641-1653, 2019.  PMID: 30721156; PMCID: PMC6436899
  5. White KA, Swier VJ, Kohlmeyer JL, Meyerholz DK, Tanas MR, Uthoff J, Rohret FA, Goeken A, Chan C-H, Leidinger MR, Umesalma, S, Wallace MR, Dodd RD, Panzer K, Darbro BW, Moutal A, Cai S, Li W, Bellampalli SS, Khanna R, Rogers CS, Sieren JC, Quelle DE, and Weimer JM.: A porcine model of neurofibromatosis type 1 that mimics the human disease. JCI Insight. 3(12):e120402, 2018.  PMID: 29925695; PMCID: PMC6124439