Welcome to the Najafov Lab:

an intersection of cell death, metabolism, and immunotherapy research


The mission of the Najafov Lab is to understand the molecular mechanisms of cell fate and the role of cell death in physiology and disease. Our research is currently focused on the cellular and molecular mechanisms of necroptosis, its role in tumorigenesis and anti-tumor immunity, 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:


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


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


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


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


Biochemistry and Cell Signaling Mechanisms

Protein phosphorylation
Protein ubiquitination
Enzyme activity studies

Unbiased Systematic Approaches

CRISPR-based genomics
Interaction proteomics

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

  • NatureCommunications_cover   ARIH1 signaling promotes anti-tumor immunity by targeting PD-L1 for proteasomal degradation.
    Wu Y, Zhang C, Liu X ... 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]
  • Mol Cell 2020 cover   RIPK1 Promotes Energy Sensing by the mTORC1 Pathway.
    Najafov A*, Luu HS, Mookhtiar AK ... 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]
  • NatureCommunications_cover   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]
  • Mol Cell 2019 cover   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]
  • Bioinformatics cover   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]
  • PlosBiology2018 cover   BRAF and AXL oncogenes drive RIPK3 expression loss in cancer.
    Najafov A*, Zervantonakis IK, Mookhtiar AK ... 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]
  • GenesDev cover   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 cover   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]
  • Trends in Cancer cover   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]
  • Science2016 cover   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]
  • Cell 2016 cover   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]


    Lab Members

    Ayaz Najafov, Ph.D.

    Assistant Professor
    About the PI

    Lorien Shropshire, B.A.

    Sr. Administrative Assistant II
    About Lorien

    Zeena Hashem, B.Sc.

    Research Assistant I
    About Zeena

    Magda Grzemska, Ph.D.

    About Magda

    Kimberly Wood, M.Sc.

    Research Technician II
    About Kimberly

    Shehreen Amjad, Ph.D.

    About Shehreen

    Hyunjin Noh, Ph.D.

    About Hyunjin


    If you are a graduate student at UT Southwestern and would like to do a lab rotation, please contact the PI by email.
    If you would like to apply for a postdoc position in the lab, please email your CV and cover letter to the PI.

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