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 necroptosis and how it 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 various 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 necroptosis occurs through cell membrane rupture by large pores formed via RIPK3-triggered phosphorylation and tetramerization of a pseudokinase MLKL.

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

We are interested in answering these fundamental questions:

Necroptosis Signaling

What is the molecular architecture of the necroptosis signaling? What drives and what inhibits necroptotic cell death?

Necroptosis and Cancer

Cancer cells gain resistance to necroptosis. What is the mechanism of this escape from necroptosis? What is the contribution of this escape to tumorigenesis?

Necroptosis and Immunity

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

Genome-wide screens
Interaction proteomics
Phosphoproteomics

Bioinformatics & Computational Bio

Motifs & big data analysis
Genetic algorithms
Machine learning

In vivo Models of Human Diseases

Cancer models
Sepsis models
Inflammation models




Selected Publications


Research Articles

  • 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]


  • 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]


Reviews

  • 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]

  • 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]

  • 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, PhD

Principal Invesigator
Assistant Professor
About the PI | Email

Elena Boms, MSc

Research Assistant
About Elena
Email

Claire Rozada, BSc

Research Technician II
About Claire
Email




Doğan Can Kırman, PhD

Postdoc
About Can
Email



Contact

Connect with us on LinkedIn

Ayaz Najafov

Email Us

Ayaz.Najafov[at]UTSouthwestern.edu

Follow Us On Twitter

@AyazNajafov
© 2021 Najafov Lab. All rights reserved. This website reflects only the views of the author and is not a publication of UT Southwestern, which bears no responsibility for its content.