Group Volkan Sayin

Research summary

The Sayin lab is positioned in the intersection between lung cancer therapeutics, cancer metabolism and redox biology. We are building a precision medicine platform combining the latest technologies in lung cancer research and metabolomics to establish an extensive translational lung cancer group at Sahlgrenska Center for Cancer Research.

Some of the aims of the lab are:

1. Identifying druggable targets in RAS and RAF driven cancers by combining a high-throughput screening platform using lentiviral-CRISPR/Cas9 with metabolomics and state-of- the- art genetically engineered mouse models of lung adenocarcinoma.
    
2. Developing patient-derived xenograft (PDX) models by transplanting fresh tumor pieces subcutaneously and orthotopically in humanized-immunocompromised mice. The humanized-PDX platform has the capacity to maintain patient-derived immune cells and will be used for both experimental studies and pre-clinical trials.
    
3. Identifying redox-metabolism related weaknesses in cancer cells, as well as analyzing the impact of genetic alterations in the redox network on tumor-associated immune cells and its effect on tumor initiation and progression, and immunotherapy.

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The overarching objective of our research is to improve the quality of life and survival rates of cancer patients, guide personalized clinical trials, repurpose pre-existing drugs, and find novel combination therapies that can synergize with current standard-of-care therapies, including chemo- and immunotherapies.

Research tools and resources

Being a multifaceted lab, we use a wide range of cell- and molecular biology methods and reagents.

• We use cellular and animal models. Some of these are cancer cell lines, reporter cell lines, biosensors, primary cells and qPCR, GC-MS, IP, WB, IF/IHC, HCS microscopy, and compound screening, among many others.
   
• Our lab has developed lentiviral-CRISPR/Cas9 strategies to inactivate any gene-of-interest at tumor onset or later during tumor progression and metastasis.
   
• We have set up a genome-wide CRISPR/Cas9 platform for identifying synthetic lethal targets or novel combination therapies for cancer.

Current group members

Volkan Sayin, PhD, Associate Professor, Principal Investigator
Sama Sayin, MD, PhD, Principal Scientist
Martin Dankis, PhD, Postdoctoral Researcher
Maria Schwarz, PhD, Postdoctoral Researcher
Ella Äng, MD, PhD student
Kevin Ali, MSc, PhD student
Angana Patel, MSc, PhD student
Jozefina Dzanan, MSc, PhD student

Selected publications

1. Activation of Oxidative Stress Response in Cancer Generates a Druggable Dependency on Exogenous Non-essential Amino Acids.
   LeBoeuf SE, Wu WL, Karakousi TR, Karadal B, Jackson SR, Davidson SM, Wong KK, Koralov SB, Sayin VI, Papagiannakopoulos T. Cell Metab. 2019 Nov 28. pii: S1550-4131(19)30619-9. doi: 10.1016/j.cmet.2019.11.012.
    
2. Protein prenylation restrains innate immunity by inhibiting Rac1 effector interactions.
   Akula MK, Ibrahim MX, Ivarsson EG, Khan OM, Kumar IT, Erlandsson M, Karlsson C, Xu X, Brisslert M, Brakebusch C, Wang D, Bokarewa M, Sayin VI, Bergo MO. Nat Commun. 2019 Sep 4;10(1):3975. doi: 10.1038/s41467-019-11606-x.
    
3. BACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis.
   Wiel C, Le Gal K, Ibrahim MX, Jahangir CA, Kashif M, Yao H, Ziegler DV, Xu X, Ghosh T, Mondal T, Kanduri C, Lindahl P, Sayin VI*, Bergo MO. Cell. 2019 Jul 11;178(2):330-345.e22. doi: 10.1016/j.cell.2019.06.005. Epub 2019 Jun 27.*Co-Corresponding
    
4. Nrf2 Activation Promotes Lung Cancer Metastasis by Inhibiting the Degradation of Bach1.
   Lignitto L, LeBoeuf SE, Homer H, Jiang S, Askenazi M, Karakousi TR, Pass HI, Bhutkar AJ, Tsirigos A, Ueberheide B, Sayin VI, Papagiannakopoulos T, Pagano M. Cell. 2019 Jul 11;178(2):316-329.e18. doi: 10.1016/j.cell.2019.06.003. Epub 2019 Jun 27.
    
5. Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis.
   Romero R*, Sayin VI*, Davidson SM, Bauer MR, Singh SX, LeBoeuf SE, Karakousi TR, Ellis DC, Bhutkar A, Sánchez-Rivera FJ, Subbaraj L, Martinez B, Bronson RT, Prigge JR, Schmidt EE, Thomas CJ, Goparaju C, Davies A, Dolgalev I, Heguy A, Allaj V, Poirier JT, Moreira AL, Rudin CM, Pass HI, Vander Heiden MG, Jacks T, Papagiannakopoulos T. Nature Medicine 2017 Nov;23(11):1362-1368. doi: 10.1038/nm.4407. Epub 2017 Oct 2. *Co-First
    
6. Activation of the NRF2 antioxidant program generates an imbalance in central carbon metabolism in cancer.
   Sayin VI, LeBoeuf SE, Singh SX, Davidson SM, Biancur D, Guzelhan BS, Alvarez SW, Wu WL, Karakousi TR, Zavitsanou AM, Ubriaco J, Muir A, Karagiannis D, Morris PJ, Thomas CJ, Possemato R, Vander Heiden MG, Papagiannakopoulos T. Elife. 2017 Oct 2;6. pii: e28083. doi: 10.7554/eLife.28083.
    
7. Targeting Metabolic Bottlenecks in Lung Cancer.
   Sayin VI, LeBoeuf SE, Papagiannakopoulos T. Trends in Cancer. 2019 Aug;5(8):457-459. doi: 10.1016/j.trecan.2019.06.001. Epub 2019 Jun 27.
    

More group Volkan Sayin publications on PubMed