Related Disease
Breast Cancer, Cancer, Lung Cancer, Molecular Biology
Phenomena or Processes
Cancer Biology, Cancer Epigenetics, Cell Biology, Cell Cycle Progression, Cell Signaling, Genomic Instability, Innate Immunity, Metastasis, Posttranslational Modification, Proteolytic Pathways
Research Models
Cultured Cell Lines, Human Cell Lines, Mouse, Mouse Cell Lines
Techniques and Technologies
Cell Biology, Drug Discovery, Gene Knockout (Complete and Conditional), In vivo Modeling
“Despite recent advances in treatment, patients with advanced metastatic cancers have few treatment options. Our lab is focused on developing new effective and non-toxic treatments for these patients.”
Dr. Spruck’s laboratory is focused on developing new, effective, and non-toxic treatments for patients with advanced cancers. The lab focuses on defining the molecular networks that regulate cancer cell division and drive metastasis progression. Recent studies have focused on viral mimicry as a therapeutic approach in cancer, which involves the activation of dormant endogenous retroviruses and retrotransposons in cancer cells to enhance immunogenicity and the effectiveness of immune checkpoint blockade immunotherapy and DNA damaging therapies. The laboratory utilizes various biochemical and molecular approaches, CRISPR gene editing, and animal models of cancer. An emphasis is on studies of breast, lung, prostate, and brain tumors.
Charles Spruck’s Research Report
Developing viral mimicry therapeutic approaches for cancer: Approximately 45% of the human genome is composed of repetitive elements (REs), including endogenous retroviruses and retrotransposons, that are normally transcriptionally silenced in somatic cells. Recent studies suggest that the transcriptional awakening of ERVs/retrotransposons beyond a threshold level of tolerance in cancer cells induces antiviral responses that can enhance the efficacy of certain therapies, including immunotherapy. We recently discovered a novel epigenetic regulatory pathway, FBXO44/SUV39H1, that is essential for ERV/retrotransposon silencing in cancer cells. Preclinical studies showed that FBXO44/SUV39H1 inactivation induces viral mimicry in cancer cells, leading to increased immunogenicity, decreased tumorigenicity, and enhanced the efficacy of immune checkpoint blockade therapy. We are currently exploring therapeutic approaches to target this pathway, and others like it, to prevent tumor growth and enhance immunotherapy response. We are also exploring the role of reactivated REs in human diseases.
Targeting metastatic tumors: Metastasis is a major cause of mortality in cancer. Through genomic screens and biochemical studies, we are identifying novel molecular pathways that drive cancer cell motility, invasion, and metastasis. Recently, we identified a novel molecular axis, FBXO7/EYA2-SCF(FBXW7), that promotes cancer cell motility and cancer stem cell self-renewal and suppresses cancer cell immunogenicity. Targeting this axis prevented metastasis progression, reduced the cancer stem cell population, and stimulated anti-tumor immune responses in preclinical mouse breast cancer models.
