Charles Spruck's Research Focus
"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.
Charles Spruck's Bio
Charles Spruck earned his B.S. in Biology at UCLA and Ph.D. in Molecular Biology at the University of Southern California. He worked as a postdoctoral fellow at The Scripps Research Institute in La Jolla and was recruited to the Sidney Kimmel Cancer Center in San Diego as an Assistant Professor in 2003. He joined Sanford Burnham Prebys in 2010.
Education and Training
2003: Post-doc, The Scripps Research Institute
1986: Ph.D., University of Southern California
1995; B.S., University of California at Los Angeles
Prestigious Funding Awards / Major Collaborative Grants
NIH/NCI DoD BCRP CBCRP TRDRP
Honors and Recognition
ACS Scholar
Publications
FBXO44 promotes DNA replication-coupled repetitive element silencing in cancer cells.
Shen JZ, Qiu Z, Wu Q, Finlay D, Garcia G, Sun D, Rantala J, Barshop W, Hope JL, Gimple RC, Sangfelt O, Bradley LM, Wohlschlegel J, Rich JN, Spruck C
Cell 2021 Jan 21 ;184(2):352-369.e23
A FBXO7/EYA2-SCFFBXW7 axis promotes AXL-mediated maintenance of mesenchymal and immune evasion phenotypes of cancer cells.
Shen JZ, Qiu Z, Wu Q, Zhang G, Harris R, Sun D, Rantala J, Barshop WD, Zhao L, Lv D, Won KA, Wohlschlegel J, Sangfelt O, Laman H, Rich JN, Spruck C
Mol Cell 2022 Mar 17 ;82(6):1123-1139.e8
Transcription Elongation Machinery Is a Druggable Dependency and Potentiates Immunotherapy in Glioblastoma Stem Cells.
Qiu Z, Zhao L, Shen JZ, Liang Z, Wu Q, Yang K, Min L, Gimple RC, Yang Q, Bhargava S, Jin C, Kim C, Hinz D, Dixit D, Bernatchez JA, Prager BC, Zhang G, Dong Z, Lv D, Wang X, Kim LJY, Zhu Z, Jones KA, Zheng Y, Wang X, Siqueira-Neto JL, Chavez L, Fu XD, Spruck C, Rich JN
Cancer Discov 2022 Feb ;12(2):502-521
A FBXO7/EYA2-SCFFBXW7 axis promotes AXL-mediated maintenance of mesenchymal and immune evasion phenotypes of cancer cells.
Shen JZ, Qiu Z, Wu Q, Zhang G, Harris R, Sun D, Rantala J, Barshop WD, Zhao L, Lv D, Won KA, Wohlschlegel J, Sangfelt O, Laman H, Rich JN, Spruck C
Mol Cell 2022 Mar 17 ;82(6):1123-1139.e8
Transcription Elongation Machinery Is a Druggable Dependency and Potentiates Immunotherapy in Glioblastoma Stem Cells.
Qiu Z, Zhao L, Shen JZ, Liang Z, Wu Q, Yang K, Min L, Gimple RC, Yang Q, Bhargava S, Jin C, Kim C, Hinz D, Dixit D, Bernatchez JA, Prager BC, Zhang G, Dong Z, Lv D, Wang X, Kim LJY, Zhu Z, Jones KA, Zheng Y, Wang X, Siqueira-Neto JL, Chavez L, Fu XD, Spruck C, Rich JN
Cancer Discov 2022 Feb ;12(2):502-521
Targeting FBXO44/SUV39H1 elicits tumor cell-specific DNA replication stress and viral mimicry.
Shen JZ, Spruck C
Cell Stress 2021 Feb 18 ;5(3):37-39
FBXO44 promotes DNA replication-coupled repetitive element silencing in cancer cells.
Shen JZ, Qiu Z, Wu Q, Finlay D, Garcia G, Sun D, Rantala J, Barshop W, Hope JL, Gimple RC, Sangfelt O, Bradley LM, Wohlschlegel J, Rich JN, Spruck C
Cell 2021 Jan 21 ;184(2):352-369.e23
Triple‑negative breast cancer therapy: Current and future perspectives (Review).
Won KA, Spruck C
Int J Oncol 2020 Dec ;57(6):1245-1261
PTEN and DNA-PK determine sensitivity and recovery in response to WEE1 inhibition in human breast cancer.
Brunner A, Suryo Rahmanto A, Johansson H, Franco M, Viiliäinen J, Gazi M, Frings O, Fredlund E, Spruck C, Lehtiö J, Rantala JK, Larsson LG, Sangfelt O
Elife 2020 Jul 6 ;9
