Macpherson Lab
Principal Investigator: David Macpherson
Institution: Fred Hutch Cancer Center (Seattle, WA)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
SUMMARY Small cell lung cancer (SCLC) is a lethal tumor type characterized by exquisite response to chemotherapy followed by rapid emergence of chemoresistance. Addition of PDL-1 inhibition to platinum/etoposide chemotherapy leads to improved clinical responses but only a small subset of SCLC patients benefit. Distinct subsets of SCLC have been identified including high-neuroendocrine and low-neuroendocrine (NE) subtypes. High-NE SCLC, expressing high levels of ASCL1 (SCLC-A) or NEUROD1 (SCLC-N) is best understood, with genetically engineered mouse models available. However, our understanding of low-NE subtypes is poor, owing in part to a lack of mouse models. A low-NE immune “inflamed” subset of SCLC (SCLC-I) exhibited increased response to immune checkpoint blockade and high expression of RE-1 Silencing Element (REST), a suppressor of neuronal and neuroendocrine gene expression. Aim 1 tests hypotheses that REST overexpression in a mouse model of SCLC will result in low-NE SCLC and that REST increases immunogenicity. We will use gain and loss of function studies to dissect the contribution of REST to SCLC and to model low-NE SCLC. RNA-seq analyses will use data from mouse GEM mode…
Active NIH Awards
- 5R01CA287573-03: Interrogating roles for REST in small cell lung cancer therapy response and resistance (2026)
- 1R01CA305981-01A1: Impact of KEAP1/NRF2 on therapy response in lung neuroendocrine cancers (2026)
- 5R01CA287476-02: Interrogating a novel axis of tumor suppression in small cell lung cancer (2026)
- 5R01CA281133-04: Identifying and understanding drivers of chemoresistance in small cell lung cancer (2026)
- 5P50CA228944-08: Project 3: Targeting LSD1 to augment responses to PD-L1 inhibition in small cell lung cancer (2026)
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