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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
Emre Bedel, Visiting MD
Ella Äng, MD, PhD student
Kevin Ali, MSc, PhD student
Angana Patel, MSc, PhD student
Jozefina Dzanan, MSc, PhD student

Selected publications

1. 
   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. 
   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. 
   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. 
   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. 
   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. 
   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. 
   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.