Welcome to the Najafov Lab Website

Research

The mission of the Najafov Lab is to understand the role of cell death in physiology and disease. Our research is focused on the cellular and molecular mechanisms of necroptosis and how this immunogenic programmed cell death pathway can be targeted to develop novel strategies for treating cancer.

Necroptosis is a major necrotic and inflammatory cell death linked to various human diseases, including cancer, inflammatory bowel disease, liver injury, pancreatitis, neurodegenerative disorders, and viral and bacterial infections. Necroptosis signaling is mediated by the activation of RIPK1 and RIPK3 kinases downstream of pro-inflammatory ligands such as TNF or downstream of microbial danger-associated molecules. The execution of necroptotic cell death occurs through cell membrane rupture by large transmembrane pores formed by oligomers of pseudokinase called MLKL.

Anti-tumor immunity is key for achieving sustained remission and eradication of metastasized tumors. Necroptosis is immunogenic, and necroptosis of cancer cells can be harnessed to potentiate immunotherapies, especially if induced by oncolytic viruses. Therefore, a fundamental understanding of necroptosis regulation in the context of cancer and resistance to oncolytic viruses and anti-tumor immunity could pave the way for developing future cancer immunotherapies and cancer vaccines.

We are interested in answering these fundamental questions:

Signaling

What is the molecular architecture of the necroptosis signaling? Which kinases and E3 ubiquitin ligases activate and inhibit necroptotic cell death?

Metabolism

How does cell metabolism interact with the necroptosis pathway? How can this interaction be targeted in human diseases?

Cancer

What is the mechanism of this escape from necroptosis? What is the contribution of this escape to tumorigenesis?

Immunotherapy

How can cancer cells be sensitized to necroptosis to enhance anti-tumor immunity and cancer immunotherapies?

Methods



Biochemistry and Cell Signaling Mechanisms

Protein phosphorylation
Protein ubiquitination
Enzyme activity studies

Unbiased Systematic Approaches

CRISPR-based genomics
Interaction proteomics
Phosphoproteomics

Bioinformatics & Computational Bio

Motifs & big data analysis
Genetic algorithms
Machine learning

In vivo Models of Human Diseases

Cancer models
Immunotherapy models
Sepsis models




Selected Publications


  • ARIH1 signaling promotes anti-tumor immunity by targeting PD-L1 for proteasomal degradation.
    Wu Y, Zhang C, Liu X, He Z, Shan B, Zeng Q, Zhao Q, Zhu H, Liao H, Cen X, Xu X, Zhang M, Hou T, Wang Z, Yan H, Yang S, Sun Y, Chen Y, Wu R, Xie T, Chen W, Najafov A*, Ying S*, Xia H*. (*co-corresponding author)
    Nat Commun 2021 Apr 20;12(1):2346. doi: 10.1038/s41467-021-22467-8. PMID: 33879767 [PDF]

  • RIPK1 Promotes Energy Sensing by the mTORC1 Pathway.
    Najafov A*, Luu HS, Mookhtiar AK, Mifflin L, Xia HG, Amin PP, Ordureau A, Wang H, Yuan J*. (*co-corresponding author)
    Mol Cell 2020 Nov 23:S1097-2765(20)30786-3. doi: 10.1016/j.molcel.2020.11.008. PMID: 33271062 [PDF]

  • Pharmacological targeting of MCL-1 promotes mitophagy and improves disease pathologies in an Alzheimer's disease mouse model.
    Cen X, Chen Y, Xu X, Wu R, He F, Zhao Q, Sun Q, Yi C, Wu J, Najafov A*, Xia H*. (*co-corresponding author)
    Nat Commun 2020 Nov 12;11(1):5731. doi: 10.1038/s41467-020-19547-6. PMID: 33184293 [PDF]

  • TAM Kinases Promote Necroptosis by Regulating Oligomerization of MLKL.
    Najafov A*, Mookhtiar AK, Luu HS, Ordureau A, Pan H, Amin PP, Li Y, Lu Q, Yuan J*. (*co-corresponding author)
    Mol Cell 2019 Aug 8;75(3):457-468.e4. doi: 10.1016/j.molcel.2019.05.022. PMID: 31230815 [PDF]

  • GECO: gene expression correlation analysis after genetic algorithm-driven deconvolution.
    Najafov J, Najafov A*. (*corresponding author)
    Bioinformatics 2019 Jan 1;35(1):156-159. doi: 10.1093/bioinformatics/bty623. PMID: 30010797 [PDF]

  • BRAF and AXL oncogenes drive RIPK3 expression loss in cancer.
    Najafov A*, Zervantonakis IK, Mookhtiar AK, Greninger P, March RJ, Egan RK, Luu HS, Stover DG, Matulonis UA, Benes CH, Yuan J*. (*co-corresponding author)
    PLoS Biol 2018 Aug 29;16(8):e2005756. doi: 10.1371/journal.pbio.2005756. Aug. PMID: 30157175 [PDF]

  • Necroptosis in development and diseases.
    Shan B, Pan H, Najafov A, Yuan J.
    Genes Dev 2018 Mar 1;32(5-6):327-340. doi: 10.1101/gad.312561.118.PMID: 28451648 [PDF]

  • CrossCheck: an open-source web tool for high-throughput screen data analysis.
    Najafov J, Najafov A*. (*corresponding author)
    Sci Rep 2017 Jul 19;7(1):5855. doi: 10.1038/s41598-017-05960-3. PMID: 28724888 [PDF]

  • Necroptosis and Cancer.
    Najafov A, Chen H, Yuan J.
    Trends Cancer 2017 Apr;3(4):294-301. doi: 10.1016/j.trecan.2017.03.002. PMID: 28451648 [PDF]

  • RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS.
    Ito Y, Ofengeim D, Najafov A, Das S, Saberi S ... Yuan J.
    Science 2016 Aug 5;353(6299):603-8. doi: 10.1126/science.aaf6803. PMID: 27493188 [PDF]

  • Roles of Caspases in Necrotic Cell Death.
    Yuan J, Najafov A, Py BF.
    Cell 2016 Dec 15;167(7):1693-1704. doi: 10.1016/j.cell.2016.11.047. PMID: 27984721 [PDF]


Books

  • PCR Guru: An Ultimate Benchtop Reference for Molecular Biologists. [URL]
    Najafov A*, Hoxhaj G. Academic Press, Elsevier (2016) ISBN: 9780128042311 (*corresponding author)


  • Western Blotting Guru. [URL]
    Najafov A*, Hoxhaj G. Academic Press, Elsevier (2017) ISBN: 9780128135372 (*corresponding author)

 





Lab Members

Ayaz Najafov, Ph.D.

Assistant Professor
About the PI

Christina Stevens, B.Sc.

Sr. Administrative Assistant II
About Christina

Zeena Hashem, B.Sc.

Research Technician II
About Zeena




Aastha Acharya, M.Sc.

Research Assistant I
About Aastha



Contact

  • If you are a graduate student at UTSW and would like to do a rotation in the Najafov Lab, please email us.
    We are looking forward to our first graduate student!

  • If you would like to apply for Postdoc or Research Associate/Assistant positions, please email us your CV and cover letter.
    We're looking to hire talented and highly motivated scientists.


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Ayaz Najafov

Email Us

Ayaz.Najafov[at]UTSouthwestern.edu

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