>OAbot: Open access bot: doi added to citation with #oabot.

2021-07-06T18:57:29Z

Open access bot: doi added to citation with #oabot.

New page

{{Orphan|date=December 2020}}

{{short description|Indian immunologist}}
[[File:TD Kanneganti wikipedia edit 2.jpg|thumb|Thirumala-Devi Kanneganti]]
'''Thirumala-Devi Kanneganti''' (born 18 October 1972) 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]].<ref name=":0">{{Cite web|url=https://www.stjude.org/directory/k/thirumala-devi-kanneganti.html|title=Thirumala-Devi Kanneganti, PhD|website=www.stjude.org|access-date=2019-11-17}}</ref> Her research interests include innate immunity and inflammatory cell death with a primary focus on the role of NLR proteins and inflammasomes in health and disease.<ref name=":0" />

== 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.<ref name=":1">{{Cite news|url=https://www.nytimes.com/2017/10/27/business/illness-iindia-she-fights-it.html|title=After Witnessing Illness in India, She Seeks Ways to Fight It|last=Olsen|first=Patricia R.|date=2017-10-27|work=The New York Times|access-date=2019-11-17|issn=0362-4331}}</ref><ref name=":2">{{Cite web|url=https://www.the-scientist.com/scientist-to-watch/thirumala-devi-kanneganti-immersed-in-immunology-33454|title=Thirumala-Devi Kanneganti: Immersed in Immunology|website=The Scientist Magazine|access-date=2019-11-17}}</ref> She then received her M.Sc. and PhD from [[Osmania University]] in India.<ref name=":2" />

== Career ==
Kanneganti began her career in research as a PhD student studying plant pathogens and fungal toxins.<ref name=":3">{{Cite web|url=https://www.milstein-award.org/2018/06/thirumala-devi-kanneganti/|title=Thirumala-Devi Kanneganti|date=2018-06-29|website=The Milstein Awards|access-date=2019-11-17}}</ref> 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.<ref name=":1" /><ref name=":2" /> She then transitioned to study mammalian innate immunity at the [[University of Michigan]].<ref name=":1" /><ref name=":2" /> 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.<ref name=":0" /><ref name=":2" /> 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.

== Major contributions ==

=== Discovery of NLRP3 inflammasome and PANoptosis as therapeutic targets for infectious and inflammatory diseases and cancer ===
Kanneganti is well known for her breakthrough discoveries elucidating functions of innate immune receptors, [[Inflammasome|inflammasomes]], and inflammatory cell death and for making fundamental contributions to [[Inflammasome|inflammasome biology]].<ref name=":4">{{Cite journal|last1=Kanneganti|first1=Thirumala-Devi|last2=Ozören|first2=Nesrin|last3=Body-Malapel|first3=Mathilde|last4=Amer|first4=Amal|last5=Park|first5=Jong-Hwan|last6=Franchi|first6=Luigi|last7=Whitfield|first7=Joel|last8=Barchet|first8=Winfried|last9=Colonna|first9=Marco|last10=Vandenabeele|first10=Peter|last11=Bertin|first11=John|date=2006-03-09|title=Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3|journal=Nature|volume=440|issue=7081|pages=233–236|doi=10.1038/nature04517|issn=1476-4687|pmid=16407888|bibcode=2006Natur.440..233K|doi-access=free}}</ref><ref name=":5">{{Cite journal|last1=Kuriakose|first1=Teneema|last2=Man|first2=Si Ming|last3=Malireddi|first3=R.K. Subbarao|last4=Karki|first4=Rajendra|last5=Kesavardhana|first5=Sannula|last6=Place|first6=David E.|last7=Neale|first7=Geoffrey|last8=Vogel|first8=Peter|last9=Kanneganti|first9=Thirumala-Devi|date=2016-08-05|title=ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways|journal=Science Immunology|volume=1|issue=2|pages=aag2045|doi=10.1126/sciimmunol.aag2045|issn=2470-9468|pmc=5131924|pmid=27917412}}</ref><ref name=":6">{{Cite journal|last1=Samir|first1=Parimal|last2=Kesavardhana|first2=Sannula|last3=Patmore|first3=Deanna M.|last4=Gingras|first4=Sebastien|last5=Malireddi|first5=R. K. Subbarao|last6=Karki|first6=Rajendra|last7=Guy|first7=Clifford S.|last8=Briard|first8=Benoit|last9=Place|first9=David E.|last10=Bhattacharya|first10=Anannya|last11=Sharma|first11=Bhesh Raj|date=September 2019|title=DDX3X acts as a live-or-die checkpoint in stressed cells by regulating NLRP3 inflammasome|journal=Nature|volume=573|issue=7775|pages=590–594|doi=10.1038/s41586-019-1551-2|issn=1476-4687|pmid=31511697|pmc=6980284|bibcode=2019Natur.573..590S}}</ref><ref name=":7">{{Cite journal|last1=Karki|first1=Rajendra|last2=Lee|first2=Ein|last3=Place|first3=David|last4=Samir|first4=Parimal|last5=Mavuluri|first5=Jayadev|last6=Sharma|first6=Bhesh Raj|last7=Balakrishnan|first7=Arjun|last8=Malireddi|first8=R. K. Subbarao|last9=Geiger|first9=Rechel|last10=Zhu|first10=Qifan|last11=Neale|first11=Geoffrey|date=3 May 2018|title=IRF8 Regulates Transcription of Naips for NLRC4 Inflammasome Activation|journal=Cell|volume=173|issue=4|pages=920–933.e13|doi=10.1016/j.cell.2018.02.055|issn=1097-4172|pmc=5935577|pmid=29576451}}</ref><ref>{{Cite journal|last1=Man|first1=Si Ming|last2=Karki|first2=Rajendra|last3=Sasai|first3=Miwa|last4=Place|first4=David E.|last5=Kesavardhana|first5=Sannula|last6=Temirov|first6=Jamshid|last7=Frase|first7=Sharon|last8=Zhu|first8=Qifan|last9=Malireddi|first9=R. K. Subbarao|last10=Kuriakose|first10=Teneema|last11=Peters|first11=Jennifer L.|date=2016-10-06|title=IRGB10 Liberates Bacterial Ligands for Sensing by the AIM2 and Caspase-11-NLRP3 Inflammasomes|journal=Cell|volume=167|issue=2|pages=382–396.e17|doi=10.1016/j.cell.2016.09.012|issn=1097-4172|pmc=5074697|pmid=27693356}}</ref> 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|caspase-1]] activation, and [[Interleukin 1 beta|IL-1β]]/IL-18 maturation.<ref>{{cite web |last1=Pobojewski |first1=Sally |title=Infection-fighting protein could be key to autoimmune disease |url=http://ur.umich.edu/0506/Jan16_06/24.shtml |website=The University Record Online |publisher=University of Michigan |access-date=6 March 2020}}</ref><ref>{{cite web |last1=The Regents of the University of Michigan |title=Methods and compositions for mediation of immune responses and adjuvant activity |url=https://patents.justia.com/patent/20080008652 |website=Justia Patents |access-date=6 March 2020}}</ref> These initial studies showed that microbial components,<ref name=":4" /><ref name=":8">{{Cite journal|last1=Kanneganti|first1=Thirumala-Devi|last2=Body-Malapel|first2=Mathilde|last3=Amer|first3=Amal|last4=Park|first4=Jong-Hwan|last5=Whitfield|first5=Joel|last6=Franchi|first6=Luigi|last7=Taraporewala|first7=Zenobia F.|last8=Miller|first8=David|last9=Patton|first9=John T.|last10=Inohara|first10=Naohiro|last11=Núñez|first11=Gabriel|date=2006-12-01|title=Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA|journal=The Journal of Biological Chemistry|volume=281|issue=48|pages=36560–36568|doi=10.1074/jbc.M607594200|issn=0021-9258|pmid=17008311|doi-access=free}}</ref><ref name=":9">{{Cite journal|last1=Franchi|first1=Luigi|last2=Amer|first2=Amal|last3=Body-Malapel|first3=Mathilde|last4=Kanneganti|first4=Thirumala-Devi|last5=Ozören|first5=Nesrin|last6=Jagirdar|first6=Rajesh|last7=Inohara|first7=Naohiro|last8=Vandenabeele|first8=Peter|last9=Bertin|first9=John|last10=Coyle|first10=Anthony|last11=Grant|first11=Ethan P.|date=June 2006|title=Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages|journal=Nature Immunology|volume=7|issue=6|pages=576–582|doi=10.1038/ni1346|issn=1529-2908|pmid=16648852|s2cid=5846222}}</ref> ATP,<ref>{{Cite journal|last1=Mariathasan|first1=Sanjeev|last2=Weiss|first2=David S.|last3=Newton|first3=Kim|last4=McBride|first4=Jacqueline|last5=O'Rourke|first5=Karen|last6=Roose-Girma|first6=Meron|last7=Lee|first7=Wyne P.|last8=Weinrauch|first8=Yvette|last9=Monack|first9=Denise M.|last10=Dixit|first10=Vishva M.|date=2006-03-09|title=Cryopyrin activates the inflammasome in response to toxins and ATP|journal=Nature|volume=440|issue=7081|pages=228–232|doi=10.1038/nature04515|issn=1476-4687|pmid=16407890|bibcode=2006Natur.440..228M|doi-access=free}}</ref><ref>{{Cite journal|last1=Sutterwala|first1=Fayyaz S.|last2=Ogura|first2=Yasunori|last3=Szczepanik|first3=Marian|last4=Lara-Tejero|first4=Maria|last5=Lichtenberger|first5=G. Scott|last6=Grant|first6=Ethan P.|last7=Bertin|first7=John|last8=Coyle|first8=Anthony J.|last9=Galán|first9=Jorge E.|last10=Askenase|first10=Philip W.|last11=Flavell|first11=Richard A.|date=March 2006|title=Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1|journal=Immunity|volume=24|issue=3|pages=317–327|doi=10.1016/j.immuni.2006.02.004|issn=1074-7613|pmid=16546100|doi-access=free}}</ref> and MSU crystals<ref>{{Cite journal|last1=Martinon|first1=Fabio|last2=Pétrilli|first2=Virginie|last3=Mayor|first3=Annick|last4=Tardivel|first4=Aubry|last5=Tschopp|first5=Jürg|date=2006-03-09|title=Gout-associated uric acid crystals activate the NALP3 inflammasome|journal=Nature|volume=440|issue=7081|pages=237–241|doi=10.1038/nature04516|issn=1476-4687|pmid=16407889|bibcode=2006Natur.440..237M|doi-access=free}}</ref> 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.<ref name=":4" /><ref>{{Cite journal|last1=Thomas|first1=Paul G.|last2=Dash|first2=Pradyot|last3=Aldridge|first3=Jerry R.|last4=Ellebedy|first4=Ali H.|last5=Reynolds|first5=Cory|last6=Funk|first6=Amy J.|last7=Martin|first7=William J.|last8=Lamkanfi|first8=Mohamed|last9=Webby|first9=Richard J.|last10=Boyd|first10=Kelli L.|last11=Doherty|first11=Peter C.|date=2009-04-17|title=The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1|journal=Immunity|volume=30|issue=4|pages=566–575|doi=10.1016/j.immuni.2009.02.006|issn=1097-4180|pmc=2765464|pmid=19362023}}</ref><ref>{{Cite journal|last1=Karki|first1=Rajendra|last2=Man|first2=Si Ming|last3=Malireddi|first3=R. K. Subbarao|last4=Gurung|first4=Prajwal|last5=Vogel|first5=Peter|last6=Lamkanfi|first6=Mohamed|last7=Kanneganti|first7=Thirumala-Devi|date=2015-03-11|title=Concerted activation of the AIM2 and NLRP3 inflammasomes orchestrates host protection against Aspergillus infection|journal=Cell Host & Microbe|volume=17|issue=3|pages=357–368|doi=10.1016/j.chom.2015.01.006|issn=1934-6069|pmc=4359672|pmid=25704009}}</ref><ref>{{Cite journal|last1=Lamkanfi|first1=Mohamed|last2=Malireddi|first2=R. K. Subbarao|last3=Kanneganti|first3=Thirumala-Devi|date=2009-07-31|title=Fungal zymosan and mannan activate the cryopyrin inflammasome|journal=The Journal of Biological Chemistry|volume=284|issue=31|pages=20574–20581|doi=10.1074/jbc.M109.023689|issn=1083-351X|pmc=2742822|pmid=19509280}}</ref> In addition to these studies on the role of the NLRP3 inflammasome in infectious diseases, her lab also established the importance of the NLRP3 inflammasome in autoinflammatory diseases,<ref name=":20" /> intestinal inflammation,<ref name=":10">{{Cite journal|last1=Zaki|first1=Md Hasan|last2=Boyd|first2=Kelli L.|last3=Vogel|first3=Peter|last4=Kastan|first4=Michael B.|last5=Lamkanfi|first5=Mohamed|last6=Kanneganti|first6=Thirumala-Devi|date=2010-03-26|title=The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis|journal=Immunity|volume=32|issue=3|pages=379–391|doi=10.1016/j.immuni.2010.03.003|issn=1097-4180|pmc=2982187|pmid=20303296}}</ref> neuroinflammation,<ref>{{Cite journal|last1=Shaw|first1=Patrick J.|last2=Barr|first2=Maggie J.|last3=Lukens|first3=John R.|last4=McGargill|first4=Maureen A.|last5=Chi|first5=Hongbo|last6=Mak|first6=Tak W.|last7=Kanneganti|first7=Thirumala-Devi|date=2011-01-28|title=Signaling via the RIP2 adaptor protein in central nervous system-infiltrating dendritic cells promotes inflammation and autoimmunity|journal=Immunity|volume=34|issue=1|pages=75–84|doi=10.1016/j.immuni.2010.12.015|issn=1097-4180|pmc=3057380|pmid=21236705}}</ref> cancer,<ref name=":23" /> and metabolic diseases.<ref>{{Cite journal|last1=Stienstra|first1=Rinke|last2=van Diepen|first2=Janna A.|last3=Tack|first3=Cees J.|last4=Zaki|first4=Md Hasan|last5=van de Veerdonk|first5=Frank L.|last6=Perera|first6=Deshani|last7=Neale|first7=Geoffrey A.|last8=Hooiveld|first8=Guido J.|last9=Hijmans|first9=Anneke|last10=Vroegrijk|first10=Irene|last11=van den Berg|first11=Sjoerd|date=2011-09-13|title=Inflammasome is a central player in the induction of obesity and insulin resistance|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=108|issue=37|pages=15324–15329|doi=10.1073/pnas.1100255108|issn=1091-6490|pmc=3174591|pmid=21876127|bibcode=2011PNAS..10815324S}}</ref>

Kanneganti's lab has also been working on the upstream regulatory mechanisms of NLRP3 and inflammasome-induced inflammatory cell death, pyroptosis. Her lab identified [[Caspase 8|caspase-8]] and [[FADD]] as expression and activation regulators of both the canonical and non-canonical NLRP3 inflammasome/pyroptosis.<ref name=":11">{{Cite journal|last1=Gurung|first1=Prajwal|last2=Anand|first2=Paras K.|last3=Malireddi|first3=R. K. Subbarao|last4=Vande Walle|first4=Lieselotte|last5=Van Opdenbosch|first5=Nina|last6=Dillon|first6=Christopher P.|last7=Weinlich|first7=Ricardo|last8=Green|first8=Douglas R.|last9=Lamkanfi|first9=Mohamed|last10=Kanneganti|first10=Thirumala-Devi|date=2014-02-15|title=FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes|journal=Journal of Immunology |volume=192|issue=4|pages=1835–1846|doi=10.4049/jimmunol.1302839|issn=1550-6606|pmc=3933570|pmid=24453255}}</ref> This study demonstrated that the NLRP3 inflammasome/pyroptotic pathway is closely connected to the caspase-8–mediated programmed cell death pathway.<ref name=":11" /> This finding went against the dogma that existed at that time that caspase-8 and FADD were involved only in the apoptotic pathway.<ref name=":11" />

Following up on her original discovery that NLRP3 senses viral RNAs,<ref name=":8" /> her lab has discovered Z-DNA binding protein 1 (ZBP1)/DAI as an innate sensor of influenza virus upstream of the NLRP3 inflammasome/pyroptosis and also showed ZBP1 is a key regulator of apoptosis and necroptosis, establishing it as a master regulator of these cell death pathways.<ref name=":5" /><ref>{{Cite journal|last1=Kesavardhana|first1=Sannula|last2=Kuriakose|first2=Teneema|last3=Guy|first3=Clifford S.|last4=Samir|first4=Parimal|last5=Malireddi|first5=R. K. Subbarao|last6=Mishra|first6=Ashutosh|last7=Kanneganti|first7=Thirumala-Devi|date=2017-08-07|title=ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death|journal=The Journal of Experimental Medicine|volume=214|issue=8|pages=2217–2229|doi=10.1084/jem.20170550|issn=1540-9538|pmc=5551577|pmid=28634194}}</ref>

Her lab also established that transforming growth factor beta-activated kinase 1 (TAK1) can act as a master regulator that maintains cellular homeostasis by negatively regulating the NLRP3 inflammasome and pyroptosis, apoptosis, and necroptosis.<ref name=":16">{{Cite news|url=https://www.stjude.org/media-resources/news-releases/2019-medicine-science-news/key-cell-death-regulator-gets-job-done.html|title=Breaking the dogma: Key cell death regulator has more than one way to get the job done|date=2019-12-23|work=St. Jude Children's Research Hospital press release|access-date=2020-04-23}}</ref> Overall, these studies identified caspase-8, ZBP1, and TAK1 as master molecular switches of inflammasome activation/pyroptosis, apoptosis, and necroptosis and pioneered the establishment of the fundamental concept of PANoptosis ('''P'''yroptosis; '''A'''poptosis; '''N'''ecroptosis; 'optosis', a form of programmed cell death).<ref>{{Cite journal|last1=Malireddi|first1=R. K. Subbarao|last2=Kesavardhana|first2=Sannula|last3=Kanneganti|first3=Thirumala-Devi|date=2019|title=ZBP1 and TAK1: Master Regulators of NLRP3 Inflammasome/Pyroptosis, Apoptosis, and Necroptosis (PAN-optosis)|journal=Frontiers in Cellular and Infection Microbiology|language=en|volume=9|pages=406|doi=10.3389/fcimb.2019.00406|pmid=31850239|pmc=6902032|issn=2235-2988}}</ref>

PANoptosis is defined as a unique, physiologically relevant, inflammatory programmed cell death pathway activated by specific triggers and regulated by the PANoptosome complex. The PANoptosome provides a molecular scaffold for contemporaneous engagement of key molecules from pyroptosis, apoptosis, and necroptosis.<ref name=":16" /><ref name=":17">{{Cite news|url=https://www.stjude.org/media-resources/news-releases/2020-medicine-science-news/discovering-the-secrets-of-the-enigmatic-caspase-6.html|title=Discovering the secrets of the enigmatic caspase-6|date=2020-04-15|work=St. Jude Children's Research Hospital press release|access-date=2020-04-23}}</ref> Kanneganti's research group recently further elucidated the molecular mechanism 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 IAV.<ref name=":17" /> Her lab also showed that [[coronavirus]] activates PANoptosis and that inhibiting the NLRP3 inflammasome or [[GSDMD|gasdermin D]] during coronavirus infection actually increases cell death and cytokine secretion rather than decreasing them.<ref>{{Cite journal|last1=Zheng|first1=Min|last2=Williams|first2=Evan Peter|last3=Malireddi|first3=R. K. Subbarao|last4=Karki|first4=Rajendra|last5=Banoth|first5=Balaji|last6=Burton|first6=Amanda|last7=Webby|first7=Richard|last8=Channappanavar|first8=Rudragouda|last9=Jonsson|first9=Colleen Beth|last10=Kanneganti|first10=Thirumala-Devi|date=2020-08-06|title=Impaired NLRP3 inflammasome activation/pyroptosis leads to robust inflammatory cell death via caspase-8/RIPK3 during coronavirus infection|journal=Journal of Biological Chemistry|volume=295|issue=41|pages=14040–14052|doi=10.1074/jbc.ra120.015036|pmid=32763970|pmc=7549031|issn=0021-9258|doi-access=free}}</ref>

Her group went on to discover the role of PANoptosis in [[cytokine storm]], identifying [[Tumor necrosis factor|TNF]] and [[Interferon gamma|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 [[Severe acute respiratory syndrome coronavirus 2|SARS-CoV-2]] infection, [[septic shock]], [[hemophagocytic lymphohistiocytosis]], and cytokine shock in mice.<ref name=":19">{{Cite web|title=In the lab, St. Jude scientists identify possible COVID-19 treatment|url=https://www.stjude.org/media-resources/news-releases/2020-medicine-science-news/in-the-lab-st-jude-scientists-identify-possible-covid-19-treatment.html|access-date=2020-11-19|website=www.stjude.org|language=en}}</ref> 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 inhibit the cytokine storm and pathogenesis.<ref name=":19" /> Overall, work from Kannegant's lab has implicated PANoptosis in infectious, metabolic, neurologic, and autoinflammatory diseases and cancer.<ref name=":5" /><ref name=":16" /><ref name=":17" /><ref>{{Cite journal|last1=Karki|first1=Rajendra|last2=Sharma|first2=Bhesh Raj|last3=Lee|first3=Ein|last4=Banoth|first4=Balaji|last5=Malireddi|first5=R.K. Subbarao|last6=Samir|first6=Parimal|last7=Tuladhar|first7=Shraddha|last8=Mummareddy|first8=Harisankeerth|last9=Burton|first9=Amanda R.|last10=Vogel|first10=Peter|last11=Kanneganti|first11=Thirumala-Devi|date=2020-06-18|title=Interferon regulatory factor 1 regulates PANoptosis to prevent colorectal cancer|journal=JCI Insight|volume=5|issue=12|doi=10.1172/jci.insight.136720|pmid=32554929|pmc=7406299|issn=2379-3708|doi-access=free}}</ref><ref name=":20">{{Cite web|title=Diet affects mix of intestinal bacteria and the risk of inflammatory bone disease|url=https://www.stjude.org/media-resources/news-releases/2014-medicine-science-news/diet-affects-mix-of-intestinal-bacteria-and-the-risk-of-inflammatory-bone-disease.html|access-date=2020-09-11|website=www.stjude.org|language=en}}</ref><ref name=":19" /><ref>{{Cite web|title=Research reveals how a fungal infection activates inflammation|url=https://www.stjude.org/media-resources/news-releases/2020-medicine-science-news/research-reveals-how-a-fungal-infection-activates-inflammation.html|access-date=2021-02-12|website=www.stjude.org|language=en}}</ref>

=== 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.<ref name=":13">{{Cite journal|last1=Lukens|first1=John R.|last2=Gross|first2=Jordan M.|last3=Calabrese|first3=Christopher|last4=Iwakura|first4=Yoichiro|last5=Lamkanfi|first5=Mohamed|last6=Vogel|first6=Peter|last7=Kanneganti|first7=Thirumala-Devi|date=2014-01-21|title=Critical role for inflammasome-independent IL-1β production in osteomyelitis|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=111|issue=3|pages=1066–1071|doi=10.1073/pnas.1318688111|issn=1091-6490|pmc=3903206|pmid=24395792|bibcode=2014PNAS..111.1066L}}</ref><ref name=":21">{{Cite journal|last1=Lukens|first1=John R.|last2=Gurung|first2=Prajwal|last3=Vogel|first3=Peter|last4=Johnson|first4=Gordon R.|last5=Carter|first5=Robert A.|last6=McGoldrick|first6=Daniel J.|last7=Bandi|first7=Srinivasa Rao|last8=Calabrese|first8=Christopher R.|last9=Vande Walle|first9=Lieselotte|last10=Lamkanfi|first10=Mohamed|last11=Kanneganti|first11=Thirumala-Devi|date=2014-12-11|title=Dietary modulation of the microbiome affects autoinflammatory disease|journal=Nature|volume=516|issue=7530|pages=246–249|doi=10.1038/nature13788|issn=1476-4687|pmc=4268032|pmid=25274309|bibcode=2014Natur.516..246L}}</ref> Additionally, discoveries from her research group suggest that IL-1α and IL-1β can have distinct roles in driving inflammatory disease.<ref name=":14">{{Cite journal|last1=Lukens|first1=John R.|last2=Vogel|first2=Peter|last3=Johnson|first3=Gordon R.|last4=Kelliher|first4=Michelle A.|last5=Iwakura|first5=Yoichiro|last6=Lamkanfi|first6=Mohamed|last7=Kanneganti|first7=Thirumala-Devi|date=2013-06-13|title=RIP1-driven autoinflammation targets IL-1α independently of inflammasomes and RIP3|journal=Nature|volume=498|issue=7453|pages=224–227|doi=10.1038/nature12174|issn=1476-4687|pmc=3683390|pmid=23708968|bibcode=2013Natur.498..224L}}</ref> She identified the role of the IL-1α and RIPK1/TAK1/SYK signaling pathway in skin inflammation.<ref name=":14" /> Furthermore, her studies also showed the role of another IL-1 family member, IL-33, in regulating immune responses and microbiota in the gut.<ref name=":15">{{Cite journal|last1=Malik|first1=Ankit|last2=Sharma|first2=Deepika|last3=Zhu|first3=Qifan|last4=Karki|first4=Rajendra|last5=Guy|first5=Clifford S.|last6=Vogel|first6=Peter|last7=Kanneganti|first7=Thirumala-Devi|date=1 December 2016|title=IL-33 regulates the IgA-microbiota axis to restrain IL-1α-dependent colitis and tumorigenesis|journal=The Journal of Clinical Investigation|volume=126|issue=12|pages=4469–4481|doi=10.1172/JCI88625|issn=1558-8238|pmc=5127671|pmid=27775548}}</ref> Overall, Kanneganti's lab discovered distinct and previously unrecognized functions of cytokines IL-1α, IL-1b, and IL-33 and their signaling pathways in inflammatory diseases and cancer.<ref name=":12">{{Cite journal|last1=Lukens|first1=John R.|last2=Gross|first2=Jordan M.|last3=Kanneganti|first3=Thirumala-Devi|date=2012|title=IL-1 family cytokines trigger sterile inflammatory disease|journal=Frontiers in Immunology|volume=3|pages=315|doi=10.3389/fimmu.2012.00315|issn=1664-3224|pmc=3466588|pmid=23087690}}</ref><ref name=":13" /><ref name=":14" /><ref name=":15" /><ref name=":22">{{Cite journal|last1=Gurung|first1=Prajwal|last2=Burton|first2=Amanda|last3=Kanneganti|first3=Thirumala-Devi|date=2016-04-19|title=NLRP3 inflammasome plays a redundant role with caspase 8 to promote IL-1β-mediated osteomyelitis|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=113|issue=16|pages=4452–4457|doi=10.1073/pnas.1601636113|issn=1091-6490|pmc=4843439|pmid=27071119|bibcode=2016PNAS..113.4452G}}</ref>

Beyond her studies on IL-1 family members, her recent work on cytokine storm established TNF and IFN-γ as they key upstream cytokines that cause inflammatory cell death (PANoptosis), tissue and organ damage, and mortality and suggest that strategies to target these cytokines or other molecules in their signaling pathway should be evaluated as therapeutic strategies in [[Coronavirus disease 2019|COVID-19]], sepsis, and other diseases associated with cytokine storm.<ref name=":19" />

== Honors ==

* American Association of Immunology-BD Biosciences Investigator Award (2015)<ref>{{Cite web|url=https://www.aai.org/Awards/Career-Awards/AAI-Investigator-Award/Past-Recipients.aspx|title=AAI-BD Biosciences Investigator Award|website=The American Association of Immunologists|access-date=2020-04-23}}</ref>
* Vince Kidd Memorial Mentor of the Year Award (2015)<ref name=":0" />
* Society for Leukocyte Biology Outstanding macrophage researcher Dolph O. Adams Award (2017)<ref>{{Cite web|url=https://www.leukocytebiology.org/dolph-o-adams-award|title=Dolph O. Adams Award|website=Society for Leukocyte Biology|access-date=2020-04-23}}</ref><ref name=":18">{{Cite news|last=Geiger|first=Terrence|url=https://blogs.stjude.org/progress/thirumala-devi-kanneganti-phd-honored-for-discoveries-in-immunology/|title=Thirumala-Devi Kanneganti, PhD, honored for discoveries in immunology|date=2017-10-19|work=St. Jude Progress|access-date=2020-04-23}}</ref>
* American Society for Microbiology Eli Lilly and Company-Elanco Research Award (2017)<ref name=":18" />
* Interferon and Cytokine Research Seymour & Vivian Milstein Award for Excellence (2018)<ref name=":0" /><ref name=":3" />
* Clarivates/Web of Science list of Highly Cited Researchers (2017, 2018, 2019, 2020)<ref name=":0" /><ref>{{Cite web|title=Highly Cited Researchers|url=https://hcr.clarivate.com}}</ref><ref>{{Cite web|title=St. Jude researchers among the most highly cited in 2019|url=https://www.stjude.org/media-resources/news-releases/2019-medicine-science-news/st-jude-researchers-most-highly-cited-2019.html|access-date=2020-09-11|website=www.stjude.org|language=en}}</ref><ref>{{Cite web|title=St. Jude researchers are among the most highly cited scientists in the last decade|url=https://www.stjude.org/media-resources/news-releases/2020-medicine-science-news/st-jude-researchers-are-among-most-highly-cited-scientists-in-last-decade.html|access-date=2020-11-18|website=www.stjude.org|language=en}}</ref>
* NIH R35 Outstanding Investigator Award (2020)<ref name=":23">{{Cite web|title=St. Jude immunologist Thirumala-Devi Kanneganti, Ph.D., receives NCI Outstanding Investigator Award|url=https://www.stjude.org/media-resources/news-releases/2020-medicine-science-news/st-jude-immunologist-thirumala-devi-kanneganti-phd-receives-nci-outstanding-investigator-award.html|access-date=2020-10-03|website=www.stjude.org|language=en}}</ref><ref>{{Cite web|date=2015-10-14|title=NCI Outstanding Investigator Award Recipients - National Cancer Institute|url=https://www.cancer.gov/grants-training/grants-funding/funding-opportunities/oia/award-recipients|access-date=2020-11-02|website=www.cancer.gov|language=en}}</ref>
*Election to Fellowship in the American Academy of Microbiology, American Society for Microbiology (2021)<ref>{{Cite web|title=65 Fellows Elected into the American Academy of Microbiology|url=https://asm.org/Press-Releases/2021/February/65-Fellows-Elected-into-the-American-Academy-of-Mi|access-date=2021-02-17|website=ASM.org|language=en}}</ref>

== References ==
{{reflist}}

{{authority control}}

{{DEFAULTSORT:Kanneganti, Thirumala-Devi}}
[[Category:1972 births]]
[[Category:Living people]]
[[Category:Women immunologists]]
[[Category:Kakatiya University alumni]]
[[Category:Scientists from Telangana]]
[[Category:St. Jude Children's Research Hospital]]
[[Category:Osmania University alumni]]
[[Category:American immunologists]]
[[Category:American academics of Indian descent]]
[[Category:Fellows of the American Academy of Microbiology]]

Thirumala-Devi Kanneganti - Revision history

>OAbot: Open access bot: doi added to citation with #oabot.