Thirumala-Devi Kanneganti

Last updated

Thirumala-Devi Kanneganti
TD Kanneganti wikipedia edit 2.jpg
Born
Kothagudem, India
Alma mater
Known for
Awards
Scientific career
Fields Immunology
Institutions St. Jude Children's Research Hospital
Website https://www.stjude.org/kanneganti

Thirumala-Devi Kanneganti is an immunologist and is the Rose Marie Thomas Endowed Chair, Vice Chair of the Department of Immunology, and Member at St. Jude Children's Research Hospital. [1] She is also Director of the Center of Excellence in Innate Immunity and Inflammation at St. Jude Children's Research Hospital. Her research interests include investigating fundamental mechanisms of innate immunity, including inflammasomes and inflammatory cell death, PANoptosis, in infectious and inflammatory disease and cancer. [1]

Contents

Early life and education

Kanneganti is from Kothagudem, Telangana (United Andhra Pradesh), India. She received her undergraduate degree from Singareni Collieries Women's College, Kothagudem at Kakatiya University, where she majored in chemistry, zoology, and botany. [2] [3] She then received her M.Sc. and PhD from Osmania University in India. [3]

Career

Kanneganti began her career in research as a PhD student studying plant pathogens and fungal toxins. [4] She then went on to do postdoctoral fellowships at the University of Wisconsin and the Ohio State University studying fungal genetics and plant innate immunity. [2] [3] She transitioned to study mammalian innate immunity at the University of Michigan. [2] [3] She joined St. Jude Children's Research Hospital as an Assistant Member in the Immunology Department in 2007, where she has focused on studying inflammasomes and cell death. [1] [3] She was promoted to a full Member in 2013. She became Vice Chair of the Immunology Department in 2016 and was endowed with the Rose Marie Thomas Endowed Chair in 2017. [5] In 2022, she also became the Director of the Center of Excellence in Innate Immunity and Inflammation at St. Jude. [5] Kanneganti is among the most "Highly Cited Researchers" in the world due to the noteworthy impact of her findings in the fields of innate immunity, inflammation, and cell death. [1] [6] [7] [8] [9] [10]

Awards and honors

Major contributions

Discovery of NLRP3 inflammasome, ZBP1-, RIPK1-, AIM2-, and NLRP12-PANoptosomes, and PANoptosis as therapeutic targets for infectious and inflammatory diseases and cancer

Kanneganti is well known for her breakthrough discoveries elucidating the functions of innate immune receptors, inflammasomes, and inflammatory cell death and for making fundamental contributions to inflammasome biology and the cell death field. [21] [22] [23] [24] [25] Her studies, along with those from other groups published in 2006, provided the first genetic evidence for the role of NLRP3 in the formation of the inflammasome, caspase-1 activation, and IL-1β/IL-18 maturation. [26] [27] These initial studies showed that microbial components, [21] [28] [29] ATP, [30] [31] and MSU crystals [32] activate the NLRP3 inflammasome.

Kanneganti discovered that Influenza A virus, Candida , and Aspergillus specifically activate the NLRP3 inflammasome and elucidated the physiological role of the NLRP3 inflammasome in host defense. [21] [33] [34] [35] [36] [37] Beyond infectious diseases, her lab also established the importance of the NLRP3 inflammasome in autoinflammatory diseases, [38] intestinal inflammation, [39] neuroinflammation, [40] cancer, [14] and metabolic diseases. [41]

Kanneganti's lab has also worked on the upstream regulatory mechanisms of NLRP3 and inflammasome-induced inflammatory cell death, pyroptosis. Her lab identified caspase-8 and FADD as expression and activation regulators of both the canonical and non-canonical NLRP3 inflammasome/pyroptosis. [42] Her group also characterized redundancies between caspase-1 and caspase-8 and between NLRP3 and caspase-8 in autoinflammatory disease and linked diet and the microbiome to these processes. [38] [43] [44] These studies demonstrated that the NLRP3 inflammasome/pyroptotic pathway is closely connected to the caspase-8–mediated programmed cell death pathway. [38] [42] [43] [44] This finding went against the dogma that existed at that time that caspase-8 and FADD were involved only in apoptosis. [42]

Following up on her original discovery that NLRP3 senses viral RNAs, [28] her lab discovered Z-DNA binding protein 1 (ZBP1)/DAI as an innate immune sensor of influenza virus upstream of the NLRP3 inflammasome and cell death; however, this cell death was not consistent with any of the cell death pathways characterized at that time. [22] [45] This led Kanneganti to characterize ZBP1 as a regulator of PANoptosis, a unique innate immune inflammatory cell death pathway driven by caspases and RIPKs that is regulated by multiprotein PANoptosome complexes. [46] The multifaceted PANoptosome complexes have been visualized in single cells to integrate several molecular components, including ASC, caspase-8, and RIPK3. [47] [48] [49] [50] [51] [52] [53]

She then went on to establish that multiple PANoptosomes can contain different sensors and respond to different triggers:

Collectively, these studies identified ZBP1, AIM2, RIPK1, NLRP12, TAK1, and caspase-8 as master molecular switches of inflammasome activation and PANoptosis. Additionally, her group discovered that interferon regulatory factor 1 (IRF1), a critical regulator of inflammation and cell death, [58] regulates the activation of PANoptosis. [59]

PANoptosis is implicated in driving innate immune responses and inflammation. Kanneganti's research group has also further elucidated the molecular mechanisms of PANoptosis and showed that the enigmatic caspase-6 is critical for ZBP1-mediated NLRP3 inflammasome activation, PANoptosis, innate immune responses, and host defense against influenza virus. [49] Her lab also showed that coronavirus activates PANoptosis and that inhibiting the NLRP3 inflammasome or gasdermin D during coronavirus infection increases cell death and cytokine secretion rather than decreasing them. [60] Her research group also recently discovered the role of NINJ1, a key executioner of inflammatory cell death, in mediating PANoptosis following heat stress and infection, thereby identifying NINJ1 and PANoptosis effectors as potential therapeutic targets. [61]

Her group has also discovered the role of PANoptosis in cytokine storm, identifying TNF and IFN-γ as key cytokines that cause this inflammatory cell death pathway and lead to lung damage, organ failure, and lethality. Kanneganti's research group also showed that inhibiting TNF and IFN-γ could prevent lethality in SARS-CoV-2 infection, septic shock, hemophagocytic lymphohistiocytosis, and cytokine shock in mice. [62] This led her to advocate for the evaluation of a strategy to repurpose approved drugs that inhibit TNF-α or IFN-γ, as well as those that target other molecules in the PANoptosis pathway (e.g., JAK), to prevent the cytokine storm and pathogenesis. [62] [63] Additional work in Kanneganti's lab focusing on beta-coronaviruses showed that IFN induces ZBP1-mediated PANoptosis, which causes morbidity and mortality. These findings led her team to suggest that inhibiting ZBP1 may improve the efficacy of IFN therapy for COVID-19 and impact other infectious and inflammatory diseases where IFNs cause pathology. [64] [46] Beyond infectious disease and inflammatory syndromes, Kanneganti's group has also found that activating PANoptosis could be beneficial to eliminating cancer cells. Treatment of cancer cells with PANoptosis-inducing agents TNF and IFN-γ can reduce tumor size in preclinical models. [62] [65] [66] Her group also discovered a regulatory relationship between ADAR1 and ZBP1 that can be targeted with the combination of nuclear export inhibitors, such as selinexor, and IFN to drive ZBP1-mediated PANoptosis and regress tumors in preclinical models. [48] [67]

Overall, work from Kanneganti's lab has implicated PANoptosis in infectious, metabolic, hemolytic, neurologic, and autoinflammatory diseases and cancer. [22] [38] [47] [48] [49] [62] [46] [56]

Cytokine signaling and disease

Kanneganti's lab showed compensatory roles for NLRP3/caspase-1 and caspase-8 in the regulation of IL-1β production in osteomyelitis. [43] [44] Additionally, discoveries from her research group suggest that IL-1α and IL-1β can have distinct roles in driving inflammatory disease. [68] She identified the role of the IL-1α and RIPK1/TAK1/SYK signaling pathways in skin inflammation. [68] Furthermore, her studies also showed the role of another IL-1 family member, IL-33, in regulating immune responses and microbiota in the gut. [69] Overall, Kanneganti's lab discovered distinct and previously unrecognized functions of the cytokines IL-1α, IL-1β, and IL-33 and their signaling pathways in inflammatory diseases and cancer. [70] [43] [68] [69] [71]

Beyond her studies on IL-1 family members, her recent work on cytokine storm established TNF and IFN-γ as the key upstream cytokines that cause inflammatory cell death (PANoptosis), tissue and organ damage, and mortality, and she has suggested that strategies to target these cytokines or other molecules in their signaling pathway should be evaluated as therapeutic strategies in COVID-19, sepsis, and other diseases associated with cytokine storm. [62]

Related Research Articles

<span class="mw-page-title-main">Caspase</span> Family of cysteine proteases

Caspases are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cysteine protease activity – a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. As of 2009, there are 12 confirmed caspases in humans and 10 in mice, carrying out a variety of cellular functions.

<span class="mw-page-title-main">Interleukin 1 beta</span> Mammalian protein found in Homo sapiens

Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the IL1B gene. There are two genes for interleukin-1 (IL-1): IL-1 alpha and IL-1 beta. IL-1β precursor is cleaved by cytosolic caspase 1 to form mature IL-1β.

<span class="mw-page-title-main">Caspase 1</span> Enzyme found in humans

Caspase-1/Interleukin-1 converting enzyme (ICE) is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines interleukin 1β and interleukin 18 as well as the pyroptosis inducer Gasdermin D, into active mature peptides. It plays a central role in cell immunity as an inflammatory response initiator. Once activated through formation of an inflammasome complex, it initiates a proinflammatory response through the cleavage and thus activation of the two inflammatory cytokines, interleukin 1β (IL-1β) and interleukin 18 (IL-18) as well as pyroptosis, a programmed lytic cell death pathway, through cleavage of Gasdermin D. The two inflammatory cytokines activated by Caspase-1 are excreted from the cell to further induce the inflammatory response in neighboring cells.

<span class="mw-page-title-main">NLRP3</span> Human protein and coding gene

NLR family pyrin domain containing 3 (NLRP3), is a protein that in humans is encoded by the NLRP3 gene located on the long arm of chromosome 1.

Pyroptosis is a highly inflammatory form of lytic programmed cell death that occurs most frequently upon infection with intracellular pathogens and is likely to form part of the antimicrobial response. This process promotes the rapid clearance of various bacterial, viral, fungal and protozoan infections by removing intracellular replication niches and enhancing the host's defensive responses. Pyroptosis can take place in immune cells and is also reported to occur in keratinocytes and some epithelial cells.

<span class="mw-page-title-main">NLRP12</span> Protein-coding gene in the species Homo sapiens

Nucleotide-binding oligomerization domain-like receptor (NLR) pyrin domain (PYD)-containing protein 12 is a protein that in humans is encoded by the NLRP12 gene.

<span class="mw-page-title-main">ZBP1</span> Protein-coding gene in the species Homo sapiens

Z-DNA-binding protein 1, also known as DNA-dependent activator of IFN-regulatory factors (DAI) and DLM-1, is a protein that in humans is encoded by the ZBP1 gene.

<span class="mw-page-title-main">AIM2</span> Protein-coding gene in the species Homo sapiens

Interferon-inducible protein AIM2 also known as absent in melanoma 2 or simply AIM2 is a protein that in humans is encoded by the AIM2 gene.

<span class="mw-page-title-main">NOD-like receptor</span> Class of proteins

The nucleotide-binding oligomerization domain-like receptors, or NOD-like receptors (NLRs), are intracellular sensors of pathogen-associated molecular patterns (PAMPs) that enter the cell via phagocytosis or pores, and damage-associated molecular patterns (DAMPs) that are associated with cell stress. They are types of pattern recognition receptors (PRRs), and play key roles in the regulation of innate immune response. NLRs can cooperate with toll-like receptors (TLRs) and regulate inflammatory and apoptotic response.

Inflammasomes are cytosolic multiprotein complexes of the innate immune system responsible for the activation of inflammatory responses and cell death. They are formed as a result of specific cytosolic pattern recognition receptors (PRRs) sensing microbe-derived pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs) from the host cell, or homeostatic disruptions. Activation and assembly of the inflammasome promotes the activation of caspase-1, which then proteolytically cleaves pro-inflammatory cytokines, interleukin 1β (IL-1β) and interleukin 18 (IL-18), as well as the pore-forming molecule gasdermin D (GSDMD). The N-terminal GSDMD fragment resulting from this cleavage induces a pro-inflammatory form of programmed cell death distinct from apoptosis, referred to as pyroptosis, which is responsible for the release of mature cytokines. Additionally, inflammasomes can act as integral components of larger cell death-inducing complexes called PANoptosomes, which drive another distinct form of pro-inflammatory cell death called PANoptosis.

<span class="mw-page-title-main">NLRP11</span> Protein-coding gene in the species Homo sapiens

NOD-like receptor family pyrin domain containing 11 is a protein that in humans is encoded by the NLRP11 gene located on the long arm of human chromosome 19q13.42. NLRP11 belongs to the NALP subfamily, part of a large subfamily of CATERPILLER. It is also known as NALP11, PYPAF6, NOD17, PAN10, and CLR19.6

NLRP (Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing), also abbreviated as NALP, is a type of NOD-like receptor. NOD-like receptors are a type of pattern recognition receptor that are found in the cytosol of the cell, recognizing signals of antigens in the cell. NLRP proteins are part of the innate immune system and detect conserved pathogen characteristics, or pathogen-associated molecular patterns, such as such as peptidoglycan, which is found on some bacterial cells. It is thought that NLRP proteins sense danger signals linked to microbial products, initiating the processes associated with the activation of the inflammasome, including K+ efflux and caspase 1 activation. NLRPs are also known to be associated with a number of diseases. Research suggests NLRP proteins may be involved in combating retroviruses in gametes. As of now, there are at least 14 different known NLRP genes in humans, which are named NLRP1 through NLRP14. The genes translate into proteins with differing lengths of leucine-rich repeat domains.

Murine caspase-11, and its human homologs caspase-4 and caspase-5, are mammalian intracellular receptor proteases activated by TLR4 and TLR3 signaling during the innate immune response. Caspase-11, also termed the non-canonical inflammasome, is activated by TLR3/TLR4-TRIF signaling and directly binds cytosolic lipopolysaccharide (LPS), a major structural element of Gram-negative bacterial cell walls. Activation of caspase-11 by LPS is known to cause the activation of other caspase proteins, leading to septic shock, pyroptosis, and often organismal death.

<span class="mw-page-title-main">GSDMD</span> Protein found in humans

Gasdermin D is a protein that in humans is encoded by the GSDMD gene on chromosome 8. It belongs to the gasdermin family which is conserved among vertebrates and comprises six members in humans, GSDMA, GSDMB, GSDMC, GSDMD, GSDME (DFNA5) and DFNB59 (Pejvakin). Members of the gasdermin family are expressed in a variety of cell types including epithelial cells and immune cells. GSDMA, GSDMB, GSDMC, GSDMD and GSDME have been suggested to act as tumour suppressors.

<span class="mw-page-title-main">Inflammaging</span> Chronic low-grade inflammation that develops with advanced age

Inflammaging is a chronic, sterile, low-grade inflammation that develops with advanced age, in the absence of overt infection, and may contribute to clinical manifestations of other age-related pathologies. Inflammaging is thought to be caused by a loss of control over systemic inflammation resulting in chronic overstimulation of the innate immune system. Inflammaging is a significant risk factor in mortality and morbidity in aged individuals.

<span class="mw-page-title-main">Vishva Dixit</span> Kenyan molecular biologist

Vishva Mitra Dixit is a physician of Indian origin who is currently Vice President and Senior Fellow of Physiological Chemistry and Research Biology at Genentech.

<span class="mw-page-title-main">Dapansutrile</span> Chemical compound

Dapansutrile (OLT1177) is an inhibitor of the NLRP3 inflammasome.

Autoinflammatory diseases (AIDs) are a group of rare disorders caused by dysfunction of the innate immune system. These responses are characterized by periodic or chronic systemic inflammation, usually without the involvement of adaptive immunity.

PANoptosis is a prominent unique, innate immune, inflammatory, and lytic cell death pathway initiated by innate immune sensors and driven by caspases and RIPKs through multiprotein PANoptosome complexes. The assembly of the PANoptosome cell death complex occurs in response to germline-encoded pattern-recognition receptors (PRRs) sensing pathogens, including bacterial, viral, and fungal infections, as well as pathogen-associated molecular patterns, damage-associated molecular patterns, and cytokines that are released during infections, inflammatory conditions, and cancer. Several PANoptosome complexes, such as the ZBP1-, AIM2-, RIPK1-, NLRC5- and NLRP12-PANoptosomes, have been characterized so far.

Jonathan C. Kagan is an American immunologist and the Marian R. Neutra, Ph.D. Professor of Pediatrics at Harvard Medical School. He is also the director of Basic Research and Shwachman Chair in Gastroenterology at Boston Children's Hospital. Kagan is a world leader in defining the molecular basis of innate immunity and inflammation.

References

  1. 1 2 3 4 5 6 7 "Thirumala-Devi Kanneganti, PhD". www.stjude.org. Retrieved 17 November 2019.
  2. 1 2 3 Olsen, Patricia R. (27 October 2017). "After Witnessing Illness in India, She Seeks Ways to Fight It". The New York Times. ISSN   0362-4331 . Retrieved 17 November 2019.
  3. 1 2 3 4 5 "Thirumala-Devi Kanneganti: Immersed in Immunology". The Scientist Magazine. Retrieved 17 November 2019.
  4. 1 2 "Thirumala-Devi Kanneganti". The Milstein Awards. 29 June 2018. Archived from the original on 26 May 2022. Retrieved 17 November 2019.
  5. 1 2 "Thirumala-Devi Kanneganti, PhD". www.stjude.org. Retrieved 12 March 2024.
  6. 1 2 "Highly Cited Researchers".
  7. 1 2 "St. Jude researchers among the most highly cited in 2019". www.stjude.org. Retrieved 11 September 2020.
  8. 1 2 "St. Jude researchers are among the most highly cited scientists in the last decade". www.stjude.org. Retrieved 18 November 2020.
  9. 1 2 Kumar, Ruma. "St. Jude scientists make prestigious list of Highly Cited Researchers". www.stjude.org. Retrieved 19 November 2021.
  10. 1 2 "'Highly cited' St. Jude scientists named to annual list". www.stjude.org. Retrieved 12 March 2024.
  11. ↑ "AAI-BD Biosciences Investigator Award". The American Association of Immunologists. Retrieved 23 April 2020.
  12. ↑ "Dolph O. Adams Award". Society for Leukocyte Biology. Retrieved 23 April 2020.
  13. 1 2 Geiger, Terrence (19 October 2017). "Thirumala-Devi Kanneganti, PhD, honored for discoveries in immunology". St. Jude Progress. Retrieved 23 April 2020.
  14. 1 2 "St. Jude immunologist Thirumala-Devi Kanneganti, Ph.D., receives NCI Outstanding Investigator Award". www.stjude.org. Retrieved 3 October 2020.
  15. ↑ "NCI Outstanding Investigator Award Recipients - National Cancer Institute". www.cancer.gov. 14 October 2015. Retrieved 2 November 2020.
  16. ↑ "65 Fellows Elected into the American Academy of Microbiology". ASM.org. Retrieved 17 February 2021.
  17. ↑ "Welcome to AAISCR". www.aaiscr.org. Retrieved 12 March 2024.
  18. ↑ Kanneganti, Thirumala-Devi (August 2023). "Rosalind Franklin Society Proudly Announces the 2022 Award Recipient for Viral Immunology". Viral Immunology. 36 (6): 367. doi:10.1089/vim.2023.29061.rfs2022. ISSN   0882-8245. S2CID   260840370.
  19. ↑ "Thirumala-Devi Kanneganti, Ph.D. named 2022 AAAS Fellow". 31 January 2023. Retrieved 16 May 2023.
  20. ↑ "AAI-Thermo Fisher Meritorious Career Award".
  21. 1 2 3 Kanneganti, Thirumala-Devi; Ozören, Nesrin; Body-Malapel, Mathilde; Amer, Amal; Park, Jong-Hwan; Franchi, Luigi; Whitfield, Joel; Barchet, Winfried; Colonna, Marco; Vandenabeele, Peter; Bertin, John (9 March 2006). "Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3". Nature. 440 (7081): 233–236. Bibcode:2006Natur.440..233K. doi: 10.1038/nature04517 . hdl: 2027.42/62569 . ISSN   1476-4687. PMID   16407888.
  22. 1 2 3 4 Kuriakose, Teneema; Man, Si Ming; Malireddi, R.K. Subbarao; Karki, Rajendra; Kesavardhana, Sannula; Place, David E.; Neale, Geoffrey; Vogel, Peter; Kanneganti, Thirumala-Devi (5 August 2016). "ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways". Science Immunology. 1 (2): aag2045. doi:10.1126/sciimmunol.aag2045. ISSN   2470-9468. PMC   5131924 . PMID   27917412.
  23. ↑ Samir, Parimal; Kesavardhana, Sannula; Patmore, Deanna M.; Gingras, Sebastien; Malireddi, R. K. Subbarao; Karki, Rajendra; Guy, Clifford S.; Briard, Benoit; Place, David E.; Bhattacharya, Anannya; Sharma, Bhesh Raj (September 2019). "DDX3X acts as a live-or-die checkpoint in stressed cells by regulating NLRP3 inflammasome". Nature. 573 (7775): 590–594. Bibcode:2019Natur.573..590S. doi:10.1038/s41586-019-1551-2. ISSN   1476-4687. PMC   6980284 . PMID   31511697.
  24. ↑ Karki, Rajendra; Lee, Ein; Place, David; Samir, Parimal; Mavuluri, Jayadev; Sharma, Bhesh Raj; Balakrishnan, Arjun; Malireddi, R. K. Subbarao; Geiger, Rechel; Zhu, Qifan; Neale, Geoffrey (3 May 2018). "IRF8 Regulates Transcription of Naips for NLRC4 Inflammasome Activation". Cell. 173 (4): 920–933.e13. doi:10.1016/j.cell.2018.02.055. ISSN   1097-4172. PMC   5935577 . PMID   29576451.
  25. ↑ Man, Si Ming; Karki, Rajendra; Sasai, Miwa; Place, David E.; Kesavardhana, Sannula; Temirov, Jamshid; Frase, Sharon; Zhu, Qifan; Malireddi, R. K. Subbarao; Kuriakose, Teneema; Peters, Jennifer L. (6 October 2016). "IRGB10 Liberates Bacterial Ligands for Sensing by the AIM2 and Caspase-11-NLRP3 Inflammasomes". Cell. 167 (2): 382–396.e17. doi:10.1016/j.cell.2016.09.012. ISSN   1097-4172. PMC   5074697 . PMID   27693356.
  26. ↑ Pobojewski, Sally. "Infection-fighting protein could be key to autoimmune disease". The University Record Online. University of Michigan. Retrieved 6 March 2020.
  27. ↑ The Regents of the University of Michigan. "Methods and compositions for mediation of immune responses and adjuvant activity". Justia Patents. Retrieved 6 March 2020.
  28. 1 2 Kanneganti, Thirumala-Devi; Body-Malapel, Mathilde; Amer, Amal; Park, Jong-Hwan; Whitfield, Joel; Franchi, Luigi; Taraporewala, Zenobia F.; Miller, David; Patton, John T.; Inohara, Naohiro; Núñez, Gabriel (1 December 2006). "Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA". The Journal of Biological Chemistry. 281 (48): 36560–36568. doi: 10.1074/jbc.M607594200 . ISSN   0021-9258. PMID   17008311.
  29. ↑ Franchi, Luigi; Amer, Amal; Body-Malapel, Mathilde; Kanneganti, Thirumala-Devi; Ozören, Nesrin; Jagirdar, Rajesh; Inohara, Naohiro; Vandenabeele, Peter; Bertin, John; Coyle, Anthony; Grant, Ethan P. (June 2006). "Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages". Nature Immunology. 7 (6): 576–582. doi:10.1038/ni1346. ISSN   1529-2908. PMID   16648852. S2CID   5846222.
  30. ↑ Mariathasan, Sanjeev; Weiss, David S.; Newton, Kim; McBride, Jacqueline; O'Rourke, Karen; Roose-Girma, Meron; Lee, Wyne P.; Weinrauch, Yvette; Monack, Denise M.; Dixit, Vishva M. (9 March 2006). "Cryopyrin activates the inflammasome in response to toxins and ATP". Nature. 440 (7081): 228–232. Bibcode:2006Natur.440..228M. doi: 10.1038/nature04515 . ISSN   1476-4687. PMID   16407890.
  31. ↑ Sutterwala, Fayyaz S.; Ogura, Yasunori; Szczepanik, Marian; Lara-Tejero, Maria; Lichtenberger, G. Scott; Grant, Ethan P.; Bertin, John; Coyle, Anthony J.; Galán, Jorge E.; Askenase, Philip W.; Flavell, Richard A. (March 2006). "Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1". Immunity. 24 (3): 317–327. doi: 10.1016/j.immuni.2006.02.004 . ISSN   1074-7613. PMID   16546100.
  32. ↑ Martinon, Fabio; Pétrilli, Virginie; Mayor, Annick; Tardivel, Aubry; Tschopp, Jürg (9 March 2006). "Gout-associated uric acid crystals activate the NALP3 inflammasome". Nature. 440 (7081): 237–241. Bibcode:2006Natur.440..237M. doi: 10.1038/nature04516 . ISSN   1476-4687. PMID   16407889.
  33. ↑ Thomas, Paul G.; Dash, Pradyot; Aldridge, Jerry R.; Ellebedy, Ali H.; Reynolds, Cory; Funk, Amy J.; Martin, William J.; Lamkanfi, Mohamed; Webby, Richard J.; Boyd, Kelli L.; Doherty, Peter C. (17 April 2009). "The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1". Immunity. 30 (4): 566–575. doi:10.1016/j.immuni.2009.02.006. ISSN   1097-4180. PMC   2765464 . PMID   19362023.
  34. ↑ Karki, Rajendra; Man, Si Ming; Malireddi, R. K. Subbarao; Gurung, Prajwal; Vogel, Peter; Lamkanfi, Mohamed; Kanneganti, Thirumala-Devi (11 March 2015). "Concerted activation of the AIM2 and NLRP3 inflammasomes orchestrates host protection against Aspergillus infection". Cell Host & Microbe. 17 (3): 357–368. doi:10.1016/j.chom.2015.01.006. ISSN   1934-6069. PMC   4359672 . PMID   25704009.
  35. ↑ Lamkanfi, Mohamed; Malireddi, R. K. Subbarao; Kanneganti, Thirumala-Devi (31 July 2009). "Fungal zymosan and mannan activate the cryopyrin inflammasome". The Journal of Biological Chemistry. 284 (31): 20574–20581. doi: 10.1074/jbc.M109.023689 . ISSN   1083-351X. PMC   2742822 . PMID   19509280.
  36. ↑ Briard, Benoit; Fontaine, Thierry; Samir, Parimal; Place, David E.; Muszkieta, Laetitia; Malireddi, R. K. Subbarao; Karki, Rajendra; Christgen, Shelbi; Bomme, Perrine; Vogel, Peter; Beau, Rémi (December 2020). "Galactosaminogalactan activates the inflammasome to provide host protection". Nature. 588 (7839): 688–692. Bibcode:2020Natur.588..688B. doi:10.1038/s41586-020-2996-z. ISSN   1476-4687. PMC   8086055 . PMID   33268895.
  37. ↑ "Research reveals how a fungal infection activates inflammation". www.stjude.org. Retrieved 19 November 2021.
  38. 1 2 3 4 "Diet affects mix of intestinal bacteria and the risk of inflammatory bone disease". www.stjude.org. Retrieved 11 September 2020.
  39. ↑ Zaki, Md Hasan; Boyd, Kelli L.; Vogel, Peter; Kastan, Michael B.; Lamkanfi, Mohamed; Kanneganti, Thirumala-Devi (26 March 2010). "The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis". Immunity. 32 (3): 379–391. doi:10.1016/j.immuni.2010.03.003. ISSN   1097-4180. PMC   2982187 . PMID   20303296.
  40. ↑ Shaw, Patrick J.; Barr, Maggie J.; Lukens, John R.; McGargill, Maureen A.; Chi, Hongbo; Mak, Tak W.; Kanneganti, Thirumala-Devi (28 January 2011). "Signaling via the RIP2 adaptor protein in central nervous system-infiltrating dendritic cells promotes inflammation and autoimmunity". Immunity. 34 (1): 75–84. doi:10.1016/j.immuni.2010.12.015. ISSN   1097-4180. PMC   3057380 . PMID   21236705.
  41. ↑ Stienstra, Rinke; van Diepen, Janna A.; Tack, Cees J.; Zaki, Md Hasan; van de Veerdonk, Frank L.; Perera, Deshani; Neale, Geoffrey A.; Hooiveld, Guido J.; Hijmans, Anneke; Vroegrijk, Irene; van den Berg, Sjoerd (13 September 2011). "Inflammasome is a central player in the induction of obesity and insulin resistance". Proceedings of the National Academy of Sciences of the United States of America. 108 (37): 15324–15329. Bibcode:2011PNAS..10815324S. doi: 10.1073/pnas.1100255108 . ISSN   1091-6490. PMC   3174591 . PMID   21876127.
  42. 1 2 3 Gurung, Prajwal; Anand, Paras K.; Malireddi, R. K. Subbarao; Vande Walle, Lieselotte; Van Opdenbosch, Nina; Dillon, Christopher P.; Weinlich, Ricardo; Green, Douglas R.; Lamkanfi, Mohamed; Kanneganti, Thirumala-Devi (15 February 2014). "FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes". Journal of Immunology. 192 (4): 1835–1846. doi:10.4049/jimmunol.1302839. ISSN   1550-6606. PMC   3933570 . PMID   24453255.
  43. 1 2 3 4 Lukens, John R.; Gross, Jordan M.; Calabrese, Christopher; Iwakura, Yoichiro; Lamkanfi, Mohamed; Vogel, Peter; Kanneganti, Thirumala-Devi (21 January 2014). "Critical role for inflammasome-independent IL-1β production in osteomyelitis". Proceedings of the National Academy of Sciences of the United States of America. 111 (3): 1066–1071. Bibcode:2014PNAS..111.1066L. doi: 10.1073/pnas.1318688111 . ISSN   1091-6490. PMC   3903206 . PMID   24395792.
  44. 1 2 3 Lukens, John R.; Gurung, Prajwal; Vogel, Peter; Johnson, Gordon R.; Carter, Robert A.; McGoldrick, Daniel J.; Bandi, Srinivasa Rao; Calabrese, Christopher R.; Vande Walle, Lieselotte; Lamkanfi, Mohamed; Kanneganti, Thirumala-Devi (11 December 2014). "Dietary modulation of the microbiome affects autoinflammatory disease". Nature. 516 (7530): 246–249. Bibcode:2014Natur.516..246L. doi:10.1038/nature13788. ISSN   1476-4687. PMC   4268032 . PMID   25274309.
  45. ↑ Kesavardhana, Sannula; Kuriakose, Teneema; Guy, Clifford S.; Samir, Parimal; Malireddi, R. K. Subbarao; Mishra, Ashutosh; Kanneganti, Thirumala-Devi (7 August 2017). "ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death". The Journal of Experimental Medicine. 214 (8): 2217–2229. doi:10.1084/jem.20170550. ISSN   1540-9538. PMC   5551577 . PMID   28634194.
  46. 1 2 3 "ZBP1 links interferon treatment and dangerous inflammatory cell death during COVID-19". www.stjude.org. Retrieved 2 June 2022.
  47. 1 2 3 "Breaking the dogma: Key cell death regulator has more than one way to get the job done". St. Jude Children's Research Hospital press release. 23 December 2019. Retrieved 23 April 2020.
  48. 1 2 3 "Promising preclinical cancer therapy harnesses a newly discovered cell death pathway". www.stjude.org. Retrieved 19 November 2021.
  49. 1 2 3 4 "Discovering the secrets of the enigmatic caspase-6". St. Jude Children's Research Hospital press release. 15 April 2020. Retrieved 23 April 2020.
  50. ↑ Lee, SangJoon; Karki, Rajendra; Wang, Yaqiu; Nguyen, Lam Nhat; Kalathur, Ravi C.; Kanneganti, Thirumala-Devi (September 2021). "AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence". Nature. 597 (7876): 415–419. Bibcode:2021Natur.597..415L. doi:10.1038/s41586-021-03875-8. ISSN   1476-4687. PMC   8603942 . PMID   34471287.
  51. 1 2 "The PANoptosome: a new frontier in innate immune responses". www.stjude.org. Retrieved 3 June 2022.
  52. ↑ Malireddi, R. K. Subbarao; Kesavardhana, Sannula; Kanneganti, Thirumala-Devi (2019). "ZBP1 and TAK1: Master Regulators of NLRP3 Inflammasome/Pyroptosis, Apoptosis, and Necroptosis (PAN-optosis)". Frontiers in Cellular and Infection Microbiology. 9: 406. doi: 10.3389/fcimb.2019.00406 . ISSN   2235-2988. PMC   6902032 . PMID   31850239.
  53. ↑ Wang, Yaqiu; Pandian, Nagakannan; Han, Joo-Hui; Sundaram, Balamurugan; Lee, SangJoon; Karki, Rajendra; Guy, Clifford S.; Kanneganti, Thirumala-Devi (28 September 2022). "Single cell analysis of PANoptosome cell death complexes through an expansion microscopy method". Cellular and Molecular Life Sciences. 79 (10): 531. doi:10.1007/s00018-022-04564-z. ISSN   1420-9071. PMC   9545391 . PMID   36169732.
  54. ↑ Zheng, Min; Karki, Rajendra; Vogel, Peter; Kanneganti, Thirumala-Devi (30 April 2020). "Caspase-6 Is a Key Regulator of Innate Immunity, Inflammasome Activation, and Host Defense". Cell. 181 (3): 674–687.e13. doi:10.1016/j.cell.2020.03.040. ISSN   1097-4172. PMC   7425208 . PMID   32298652.
  55. ↑ Lee, SangJoon; Karki, Rajendra; Wang, Yaqiu; Nguyen, Lam Nhat; Kalathur, Ravi C.; Kanneganti, Thirumala-Devi (1 September 2021). "AIM2 forms a complex with Pyrin and ZBP1 to drive PANoptosis and host defense". Nature. 597 (7876): 415–419. Bibcode:2021Natur.597..415L. doi:10.1038/s41586-021-03875-8. ISSN   0028-0836. PMC   8603942 . PMID   34471287.
  56. 1 2 "St. Jude finds NLRP12 as a new drug target for infection, inflammation and hemolytic diseases". www.stjude.org. Retrieved 1 September 2023.
  57. ↑ Sundaram, Balamurugan; Pandian, Nagakannan; Mall, Raghvendra; Wang, Yaqiu; Sarkar, Roman; Kim, Hee Jin; Malireddi, R. K. Subbarao; Karki, Rajendra; Janke, Laura J.; Vogel, Peter; Kanneganti, Thirumala-Devi (22 June 2023). "NLRP12-PANoptosome activates PANoptosis and pathology in response to heme and PAMPs". Cell. 186 (13): 2783–2801.e20. doi:10.1016/j.cell.2023.05.005. ISSN   1097-4172. PMC   10330523 . PMID   37267949.
  58. ↑ Fujita, T; Reis, L F; Watanabe, N; Kimura, Y; Taniguchi, T; Vilcek, J (December 1989). "Induction of the transcription factor IRF-1 and interferon-beta mRNAs by cytokines and activators of second-messenger pathways". Proceedings of the National Academy of Sciences. 86 (24): 9936–9940. Bibcode:1989PNAS...86.9936F. doi: 10.1073/pnas.86.24.9936 . ISSN   0027-8424. PMC   298617 . PMID   2557635.
  59. ↑ Sharma, Bhesh Raj; Karki, Rajendra; Rajesh, Yetirajam; Kanneganti, Thirumala-Devi (September 2023). "Immune regulator IRF1 contributes to ZBP1-, AIM2-, RIPK1-, and NLRP12-PANoptosome activation and inflammatory cell death (PANoptosis)". The Journal of Biological Chemistry. 299 (9): 105141. doi: 10.1016/j.jbc.2023.105141 . ISSN   1083-351X. PMC   10494469 . PMID   37557956.
  60. ↑ Zheng, Min; Williams, Evan Peter; Malireddi, R. K. Subbarao; Karki, Rajendra; Banoth, Balaji; Burton, Amanda; Webby, Richard; Channappanavar, Rudragouda; Jonsson, Colleen Beth; Kanneganti, Thirumala-Devi (6 August 2020). "Impaired NLRP3 inflammasome activation/pyroptosis leads to robust inflammatory cell death via caspase-8/RIPK3 during coronavirus infection". Journal of Biological Chemistry. 295 (41): 14040–14052. doi: 10.1074/jbc.ra120.015036 . ISSN   0021-9258. PMC   7549031 . PMID   32763970.
  61. ↑ Han, Joo-Hui; Karki, Rajendra; Malireddi, R. K. Subbarao; Mall, Raghvendra; Sarkar, Roman; Sharma, Bhesh Raj; Klein, Jonathon; Berns, Harmut; Pisharath, Harshan; Pruett-Miller, Shondra M.; Bae, Sung-Jin; Kanneganti, Thirumala-Devi (26 February 2024). "NINJ1 mediates inflammatory cell death, PANoptosis, and lethality during infection conditions and heat stress". Nature Communications. 15 (1): 1739. Bibcode:2024NatCo..15.1739H. doi:10.1038/s41467-024-45466-x. ISSN   2041-1723. PMC   10897308 . PMID   38409108.
  62. 1 2 3 4 5 "In the lab, St. Jude scientists identify possible COVID-19 treatment". www.stjude.org. Retrieved 19 November 2020.
  63. ↑ Karki, Rajendra; Kanneganti, Thirumala-Devi (August 2021). "The 'cytokine storm': molecular mechanisms and therapeutic prospects". Trends in Immunology. 42 (8): 681–705. doi:10.1016/j.it.2021.06.001. ISSN   1471-4981. PMC   9310545 . PMID   34217595. S2CID   235733135.
  64. ↑ Karki, Rajendra; Lee, SangJoon; Mall, Raghvendra; Pandian, Nagakannan; Wang, Yaqiu; Sharma, Bhesh Raj; Malireddi, Rk Subbarao; Yang, Dong; Trifkovic, Sanja; Steele, Jacob A.; Connelly, Jon P. (19 May 2022). "ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection". Science Immunology. 7 (74): eabo6294. doi:10.1126/sciimmunol.abo6294. ISSN   2470-9468. PMC   9161373 . PMID   35587515.
  65. ↑ Karki, Rajendra; Sharma, Bhesh Raj; Tuladhar, Shraddha; Williams, Evan Peter; Zalduondo, Lillian; Samir, Parimal; Zheng, Min; Sundaram, Balamurugan; Banoth, Balaji; Malireddi, R. K. Subbarao; Schreiner, Patrick (7 January 2021). "Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes". Cell. 184 (1): 149–168.e17. doi:10.1016/j.cell.2020.11.025. ISSN   1097-4172. PMC   7674074 . PMID   33278357.
  66. ↑ Malireddi, R. K. Subbarao; Karki, Rajendra; Sundaram, Balamurugan; Kancharana, Balabhaskararao; Lee, SangJoon; Samir, Parimal; Kanneganti, Thirumala-Devi (21 July 2021). "Inflammatory Cell Death, PANoptosis, Mediated by Cytokines in Diverse Cancer Lineages Inhibits Tumor Growth". ImmunoHorizons. 5 (7): 568–580. doi:10.4049/immunohorizons.2100059. ISSN   2573-7732. PMC   8522052 . PMID   34290111.
  67. ↑ Karki, Rajendra; Sundaram, Balamurugan; Sharma, Bhesh Raj; Lee, SangJoon; Malireddi, R. K. Subbarao; Nguyen, Lam Nhat; Christgen, Shelbi; Zheng, Min; Wang, Yaqiu; Samir, Parimal; Neale, Geoffrey (19 October 2021). "ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis". Cell Reports. 37 (3): 109858. doi:10.1016/j.celrep.2021.109858. ISSN   2211-1247. PMC   8853634 . PMID   34686350.
  68. 1 2 3 Lukens, John R.; Vogel, Peter; Johnson, Gordon R.; Kelliher, Michelle A.; Iwakura, Yoichiro; Lamkanfi, Mohamed; Kanneganti, Thirumala-Devi (13 June 2013). "RIP1-driven autoinflammation targets IL-1α independently of inflammasomes and RIP3". Nature. 498 (7453): 224–227. Bibcode:2013Natur.498..224L. doi:10.1038/nature12174. ISSN   1476-4687. PMC   3683390 . PMID   23708968.
  69. 1 2 Malik, Ankit; Sharma, Deepika; Zhu, Qifan; Karki, Rajendra; Guy, Clifford S.; Vogel, Peter; Kanneganti, Thirumala-Devi (1 December 2016). "IL-33 regulates the IgA-microbiota axis to restrain IL-1α-dependent colitis and tumorigenesis". The Journal of Clinical Investigation. 126 (12): 4469–4481. doi:10.1172/JCI88625. ISSN   1558-8238. PMC   5127671 . PMID   27775548.
  70. ↑ Lukens, John R.; Gross, Jordan M.; Kanneganti, Thirumala-Devi (2012). "IL-1 family cytokines trigger sterile inflammatory disease". Frontiers in Immunology. 3: 315. doi: 10.3389/fimmu.2012.00315 . ISSN   1664-3224. PMC   3466588 . PMID   23087690.
  71. ↑ Gurung, Prajwal; Burton, Amanda; Kanneganti, Thirumala-Devi (19 April 2016). "NLRP3 inflammasome plays a redundant role with caspase 8 to promote IL-1β-mediated osteomyelitis". Proceedings of the National Academy of Sciences of the United States of America. 113 (16): 4452–4457. Bibcode:2016PNAS..113.4452G. doi: 10.1073/pnas.1601636113 . ISSN   1091-6490. PMC   4843439 . PMID   27071119.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.