Kieren Marini, Ph.D.

Experience

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  Hudson Institute of Medical Research

  May 2016 - Jun 2017

  Research Officer

  Whole genome screening to identify mediators of Platinum chemoresistance in LUAD.Outcomes:- Designed and performed whole genome arrayed siRNA screen- Assessed hits and identified genes responsible for mediating innate resistance- Validated hits in vitro and in vivo using small molecule inhibitors- Discovered Follistatin was preventing off target kidney damage due to platinum chemotherapy whilst enhancing platinum efficacy in tumor cells- Patented combination of Follistatin and Platinum Chemotherapy- Published paper in Science Translational MedicineDevelopment of models of SCLC patient derived xenograftsOutcomes:- Collected samples from hospitals (blood, EBUS samples)- Developed PDX cohort- Stained samples to confirm diagnosis and morphology of SCLC, or NSCLC- Sequenced tumors to establish molecular phenotype- Published papers in PLoS ONE and oncogene Show less

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  University of California, San Francisco

  Jul 2017 - Jun 2023

  Postdoctoral Researcher

  Understanding the role of Notch3 in LUAD using genetic engineered mouse modelingOutcomes:- Developed multiple complex GEMMs for lung adenocarcinoma (5 Allele crosses)- Lineage traced Notch3 cells inside of tissues during tumor development or tumor progression- Collected samples, processed lungs, stained sections with biomarkers- Showed Notch3 is not expressed in epithelial cells in normal lung- Discovered Notch3 is expressed in 5% of cells and maintained across tumor progression- Ablated Notch3 cells inside of tissues during tumor development/progression- Visualized tumors, imaged and quantified tumor burden- Showed that ablating <5% of total tumor cells prevents further tumor growth and progression- Performed CITE-seq to characterize Notch expressing lung tumor cellsEvaluating the cell autonomous and non-cell autonomous effects of the decoy receptor engineered CNTFR on tumor growth and progressionOutcomes:- Developed CNTFR CRISPR/Cas9 knockout lines to investigate the cell autonomous effects of CNTFR in lung cancer- Developed mouse GEMM cell lines for syngeneic allograft models- Utilized single cell genomics and spatial transcriptomics to understand changes to composition of the tumor microenvironment after novel drug treatment (eCNTFR)- Identified biomarkers of treatment response inside of different cell populations- Discovered that treatment with eCNTFR broadly alters the TME from an immunosuppressive (tumor promoting) towards a more immune stimulatory (tumor inhibitory) microenvironment- Tested combination of eCNTFR and αPD-1 in syngeneic allograft and GEMM- Showed synergy between eCNTFR and αPD-1 with 50% of mice having a complete response- Showed eCNTFR sensitized refractory GEM model to αPD-1 therapy- Paper in Review at Nature Communications Show less