Pinar Eser, PhD (Pinar_Eser@dfci.harvard.edu) investigates novel mechanisms of resistance in post-treatment patient-derived EGFR mutant cell lines, with focus on resistance-associated phenotypes. In addition, she has been involved in establishing in vitro models of resistance using the CRISPR-Cas9 genome editing technology.
Heidi Haikala, PhD, (heidiM_haikala@dfci.harvard.edu) is studying how to prevent or revert resistance to the current EGFR-targeting therapies. This includes therapeutic strategies to directly degrade the EGFR receptor by using the ubiquitin-proteasome pathway, as well as studying new ways to vertically or in parallel block the EGFR survival signaling by using combination strategies. The research utilizes cutting-edge research models, such as 3D-culture platforms and patient-derived xenograft (PDX) models.
Yoshihisa Kobayashi, MD, PhD, (Yoshihisa_Kobayashi@DFCI.HARVARD.EDU) seeks to overcome acquired resistance to osimertinib in EGFR mutant lung cancer using CRISPR and organoid systems.
Jens Köhler, MD, (Jens_Kohler@dfci.harvard.edu) studies KRAS-driven NSCLC using commercially available cancer cell lines and patient-derived tumors to recapitulate the extremely diverse tumor landscape. His research aims to answer the question of why inhibitors targeting the MAPK pathway can be effective in some patients while they fail in others, with an emphasis on microenvironment circuitries.
Kari Kurppa, PhD, (KariJ_Kurppa@dfci.harvard.edu) works to design rational combination treatments to treat EGFR-mutant lung cancer,linking the tumor’s genomic context to its response to EGFR-targeted therapies. In addition to standard cell and molecular biology methods, Kari works on the development of several CRISPR-based genome editing and screening tools.
Jieun Son, PhD, (Jieun_Son@dfci.harvard.edu) focuses on characterizing rare HER2 mutations found in NSCLC patients. In collaboration with other DFCI investigators, she also aims to provide novel targeted therapies for EGFR/HER2 lung cancers. She is currently working on developing patient-derived ex vivo screening tools for precision medicine.
Ciric To, PhD, (CiricC_To@dfci.harvard.edu) pursues the development of non-conventional approaches to target EGFR, such as highly specific allosteric inhibitors and PROTACs in NSCLC models. Her goal is to simultaneously generate and/or identify important resistance-imparting mechanisms that emerge following treatment with allosteric inhibitors.