Charlotte Feddersen

Mentor: Adam Dupuy, PhD

Year Entered Into Program: 2014

Terminal Degree(s) Received and Year: MD, PhD 2020

Affiliations:

Anatomy and Cell Biology | Medical Scientist Training Program

Research Description

Liver Cancer: The Search for Effective Treatments

Liver cancer is globally the 6th most commonly diagnosed cancer and the 2nd most deadly cancer. There are multiple factors contributing to the deadliness of the disease, including lack of early diagnostic tests, co-morbidities (e.g. cirrhosis), and ineffective treatments, particularly for last stage-disease. Using data from a recent forward genetic screen that my lab performed, I am better characterizing the Hedgehog signaling pathway that is a driver of hepatocellular carcinoma, specifically by looking at the role of Gli2 and a potential associated gene Fign. The long-term goal of my research is to design more effective, targeted therapies for HCC.

Additionally, my research focuses on drivers of melanoma metastasis and resistance. Fortunately, melanoma treatment has recently become more effective due to the BRAF enzyme inhibitor vemurafenib and immunotherapies. However, resistance to vemurafenib occurs quickly and often and the process of metastasis is still a potential highly effective target for therapies. Thus, I would like to better understand the drivers of melanoma metastasis and vemerafinib resistance through the use of forward genetic screens using Sleeping Beauty (SB) transposon mutagenesis, and pooled shRNA and CRISPR approaches. 

Awards

  • Fellowship appointment on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2016-2017
  • Institutional fellowship support on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2015-2016
  • Fellowship appointment on the Medical Scientist Training Program (NIH T32 GM007337), University of Iowa, 2012-2014

Publications

  1. Vanneste, M., Feddersen, C.R., Varzavand, A., Zhu, E.Y., Foley, T., Zhao, L., Holt, K.H., Milhem, M., Piper, R., Stipp, C.S., Dupuy, A.J., Henry, M.D.: Functional Genomic Screening Independently Identifies CUL3 as a Mediator of Vemurafenib Resistance via Src-Rac1 Signaling Axis. Front Oncol 10:442, 2020. PMCID: PMC7169429
  2. Feddersen, C.R., Schillo, J.L., Varzavand, A., Vaughn, H.R., Wadsworth, L.S., Voigt, A.P., Zhu, E.Y., Jennings, B.M., Mullen, S.A., Bobera, J., Riordan, J.D., Stipp, C.S., Dupuy, A.J.: Src-Dependent DBL Family Members Drive Resistance to Vemurafenib in Human Melanoma. Cancer Res. 79(19):5074-5087, 2019.  PMCID: PMC6774858
  3. Guimaraes-Young, A., Feddersen, C.R., and Dupuy, A.J.: Sleeping Beauty Mouse Models of Cancer: Microenvironmental Influences on Cancer Genetics. Front Oncol. (Review) 9:611, 2019. PMCID: PMC6629774
  4. Riordan, J.D., Feddersen, C.R., Tschida, B.R., Jackson, P., Keng, V.W., Linden, M.A., Amin, K., Stipp, C.S., Largaespada, D.A., Dupuy, A.J.: Chronic Liver injury alters driver mutation profiles in hepatocellular carcinoma. Hepatology, 67(3):924-939, 2018.  PMCID: PMC5826818
  5. Rauckhorst, A.J., Gray, L.R., Sheldon, R.D., Fu, X., Pewa, A., Feddersen, C.R., Dupuy, A.J., Gibson-Corley, K.N., Cox, J.E., Burgess, S.C., Taylor, E.B.:  The mitochondrial pyruvate carrier mediates high fat diet induced increases In hepatic TCA cycle capacity. Molecular Metabolism. 6(11):1468-1479, 2017.  PMCID: PMC5681281
  6. Smith, R.P., Riordan, J.D., Feddersen, C.R., Dupuy, A.J.:  A hybrid adenoviral vector system achieves efficient long-term gene expression in the liver via piggyBac transposition. Gene Ther 26(6):377-85, 2015.  PMCID: PMC4492551
  7. Praitis, V., Simske, J., Kniss, S., Mandt, R., Imlay, L., Feddersen, C., Miller, M., Mushi, J., Liszewski, W., Weinstein, R., Chakravorty, A., Ha, D., Schacht Farrell, A., Sullivan-Wilson, A., Stock, T.:  The secretory pathway calcium ATPase PMR-1/SPCA1 has essential roles in cell migration during Caenorhabditis elegans embryonic development. PloS Genet. 9(5):e1003506, 2013. PMCID: PMC3656159 
  8. Fletcher, E., Love-Homan, L., Sobhakumari, A., Feddersen, C., Koch, A., Goel, A., A Simons, A.:  EGFR inhibition induces proinflammatory cytokines via NOX4 in HNSCC. Molecular Cancer Res 11(12):1574-84, 2013. PMCID: PMC3869882

Research