9 research outputs found
LOSS OF JAK2 REGULATION VIA VHL-SOCS1 E3 UBIQUITIN HETEROCOMPLEX UNDERLIES CHUVASH POLYCYTHEMIA
- Author
- Publication venue
- Publication date
- 01/01/2011
- Field of study
Chuvash polycythemia (CP) is a rare congenital form of polycythemia caused by homozygous R200W and H191D mutations in the von Hippel-Lindau (VHL) gene whose gene product is the principal negative regulator of hypoxia-inducible factor. However, the molecular mechanisms underlying some of the hallmark features of CP such as hypersensitivity to erythropoietin are unclear. Here, we show that VHL directly binds suppressor of cytokine signalling 1 (SOCS1) to form a heterodimeric E3 ligase that targets phosphorylated (p)JAK2 for ubiquitin-mediated destruction. In contrast, CP-associated VHL mutants have altered affinity for SOCS1 and fail to engage and degrade pJAK2. Systemic administration of a highly selective JAK2 inhibitor, TG101209, reverses the disease phenotype in vhlR200W/R200W knock-in mice, a model that faithfully recapitulates human CP. These results reveal VHL as a SOCS1-cooperative negative regulator of JAK2 and provide compelling biochemical and preclinical evidence for JAK2- targeted therapy in CP patients
Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease
- Author
- Ahmed Hanan
- Amodio Donato
- Arasi Stefania
- Bedford H Melanie
- Biggs Catherine M
- Blanchard-Rohner GĂ©raldine
- Brown-Whitehorn Terri F
- Bullens Dominique
- Burns Siobhan O
- BĂ©ziat Vivien
- Cancrini Caterina
- Casanova Jean-Laurent
- Chan Gavin Shueng Wai
- Chan Koon Wing
- Changi-Ashtiani Majid
- Chua Gilbert T
- Chung Brian Hon Yin
- Cifaldi Cristina
- Claeys Tania
- Dalmann Joshua
- Del Bel Kate L
- Delafontaine Selket
- Di Cesare Silvia
- Di Matteo Gigliola
- Finocchi Andrea
- Fornes Oriol
- Fouladvand Ali
- Fu Maggie P
- Gray Christopher J
- Heimall Jennifer
- Ho Marco Hok Kung
- Hoischen Alexander
- Izumi Kosuke
- James Alyssa E
- Jones Lauren CW
- Khleborodova Asya
- Kui Lin
- Lack Justin
- Lau Yu Lung
- Le Huong Thi Minh
- Lee Jessica J
- Lee Pamela Pui Wah
- Leung Daniel
- Liang Rui
- Lin Susan
- Liu Zhongyi
- Lu Henry Y
- Lyons Jonathan J
- Maimaris Jesmeen
- Matthews Allison
- McKinnon Margaret L
- Meyts Isabelle
- Miryounesi Mohammad
- Momenilandi Mana
- Morris Emma C
- Murrell Jill R
- Nguyen Anh Thi Van
- Niemela Julie E
- Novelli Antonio
- O'Shea John J
- Pacillo Lucia
- Palma Paolo
- Parvaneh Nima
- Passarelli Chiara
- Philippot Quentin
- Philips Rachael L
- Poon Grace Wing Kit
- Puel Anne
- Richmond Phillip A
- Rivalta Beatrice
- Rohani Pejman
- Rokni-Zadeh Hassan
- Rosa Duque Jaime Sou Da
- Rosenzweig Sergio D
- Rossi Paolo
- Sauer Kate
- Seear Michael
- Shahrooei Mohammad
- Sharma Ashish A
- Sharma Mehul
- Tam Issan Yee San
- Treat James R
- Turvey Alexandra K
- Turvey Stuart E
- van der Lee Robin
- van der Made Caspar I
- van Karnebeek Clara DM
- Vaseghi-Shanjani Maryam
- Wasserman Wyeth W
- Wong Christina Sze Man
- Wood Kathleen H
- Yang Jing
- Yang Wanling
- Yang Xingtian
- Publication venue
- 'Rockefeller University Press'
- Publication date
- 01/05/2023
- Field of study
STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder
STAT1 promotes megakaryopoiesis downstream of GATA-1 in mice
- Author
- Publication venue
- 'American Society for Clinical Investigation'
- Publication date
- Field of study
Loss of JAK2 regulation via a heterodimeric VHL-SOCS1 E3 ubiquitin ligase underlies Chuvash polycythemia
- Author
- A Pardanani
- AM Roberts
- Bing Zhou
- C Dixon
- C James
- C Lacout
- CE Stebbins
- D Ungureanu
- David A Cheresh
- Dwayne L Barber
- E van Rooijen
- EJ Baxter
- G Wernig
- H Cario
- H Suzuki
- J Chung
- J Shibata
- JH Min
- K Kominami
- K Kondo
- K Kondo
- KM Lonergan
- L Rui
- L Teofili
- Lukasz M Boba
- M Celeste Simon
- M Ivan
- M Messinezy
- M Ohh
- M Ohh
- M Ohh
- MA Hoffman
- MC Bento
- ME Lenburg
- Meredith S Irwin
- Michael Ohh
- Michele M Hickey
- MJ Percy
- MJ Percy
- MJ Percy
- MK Sarna
- MM Hickey
- MM Song
- NH Stickle
- Olga Roche
- P Jaakkola
- Pardeep Heir
- PH Maxwell
- R Kralovics
- R Tiedt
- R Zhao
- RL Levine
- Roxana I Sufan
- Ryan C Russell
- S Bellucci
- S Kamizono
- S Perrotta
- Samantha N Greer
- Samuel A Heathcote
- SC Clifford
- Severa Bunda
- SN Constantinescu
- SO Ang
- SS Watowich
- Stephanie S Sybingco
- T Kamura
- Terri D Richmond
- TG Bumm
- Vinca W K Chow
- WC Hon
- William Y Kim
- WK Rathmell
- WY Kim
- WY Kim
- X Tang
- Y Le
- Y Pastore
- YD Pastore
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Recommended from our members
Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease
- Author
- Ahmed Hanan
- Amodio Donato
- Arasi Stefania
- Bedford H Melanie
- Biggs Catherine M
- Blanchard-Rohner GĂ©raldine
- Brown-Whitehorn Terri F
- Bullens Dominique
- Burns Siobhan O
- BĂ©ziat Vivien
- Cancrini Caterina
- Casanova Jean-Laurent
- Chan Gavin Shueng Wai
- Chan Koon Wing
- Changi-Ashtiani Majid
- Chua Gilbert T
- Chung Brian Hon Yin
- Cifaldi Cristina
- Claeys Tania
- Da Rosa Duque Jaime Sou
- Dalmann Joshua
- Del Bel Kate L
- Delafontaine Selket
- Di Cesare Silvia
- Di Matteo Gigliola
- Finocchi Andrea
- Fornes Oriol
- Fouladvand Ali
- Fu Maggie P
- Gray Christopher J
- Heimall Jennifer
- Ho Marco Hok Kung
- Hoischen Alexander
- Izumi Kosuke
- James Alyssa E
- Jones Lauren CW
- Khleborodova Asya
- Kui Lin
- Lack Justin
- Lau Yu Lung
- Le Huong Thi Minh
- Lee Jessica J
- Lee Pamela Pui Wah
- Leung Daniel
- Liang Rui
- Lin Susan
- Liu Zhongyi
- Lu Henry Y
- Lyons Jonathan J
- Maimaris Jesmeen
- Matthews Allison
- McKinnon Margaret L
- Meyts Isabelle
- Miryounesi Mohammad
- Momenilandi Mana
- Morris Emma C
- Murrell Jill R
- Niemela Julie E
- Novelli Antonio
- OâShea John J
- Pacillo Lucia
- Palma Paolo
- Parvaneh Nima
- Passarelli Chiara
- Philippot Quentin
- Philips Rachael L
- Poon Grace Wing Kit
- Puel Anne
- Richmond Phillip A
- Rivalta Beatrice
- Rohani Pejman
- Rokni-Zadeh Hassan
- Rosenzweig Sergio D
- Rossi Paolo
- San Tam Issan Yee
- Sauer Kate
- Seear Michael
- Shahrooei Mohammad
- Sharma Ashish A
- Sharma Mehul
- Treat James R
- Turvey Alexandra K
- Turvey Stuart E
- van der Lee Robin
- van der Made Caspar I
- van Karnebeek Clara DM
- Van Nguyen Anh Thi
- Vaseghi-Shanjani Maryam
- Wasserman Wyeth W
- Wong Christina Sze Man
- Wood Kathleen H
- Yang Jing
- Yang Wanling
- Yang Xingtian
- Publication venue
- eScholarship, University of California
- Publication date
- 01/05/2023
- Field of study
STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder
Recommended from our members
Risk of COVID-19 after natural infection or vaccinationResearch in context
- Author
- Abad  Vanessa
- Abate  Getahun
- Abbas  Anum
- Ackerman  Jamie
- Ackerman  Ronald
- Ackermann  Jeremy
- Adams  Atoya
- Adams  Mark S.
- Adams  Michael R.
- Adelglass  Jeffrey
- Afework  Sarah
- Ahmad  Nina
- Akamine  Christine
- Ake  Julie A.
- Al-Ibrahim  Mohamed S.
- Albert  Gary
- Alcaide  Maria L.
- Alderson  Nathan
- Aleman  Lily
- Alemån  José O.
- Allaw  Mohammed
- Alva  E. Javier Pretell
- Alvarado  Hilario
- Amador  Carmen
- Andersen  James
- Anderson  Corey G.
- Anderson  Evan J.
- Anderson  Victoria R.
- Andes  David R.
- Andrasik  Michele P.
- Andree  Stephanie
- Andrews  Jeb
- Andriesen  Jessica G.
- Andriulis  Victoria
- Ansel  Jessica L.
- Anthony  Codi M.
- Antwi  Mohammed
- Arduino  Roberto C.
- Aristy  Florida
- Arnold  Valerie K.
- Arrazcaeta  Alicia
- Atmar  Robert L.
- Avworo  Ayoade
- Bacher  Christina
- Baden  Lindsey R.
- Badillo  Diana
- Bainbridge  Emma
- Baka  Michele
- Baker  Sherrie
- Balani  Bindu
- Ball  Brandy
- Bances  Karla Beatriz Tafur
- Baron  Mira
- Barranco-Santana  Elizabeth
- Bartilucci  Darlene
- Bashour  Jennifer
- Batteiger  Teresa A.
- Baudelaire  Clarisse
- Bazan  Jose A.
- Becerra  Maria G.
- Becker  Teresa
- Beckmann  David
- Bedimo  Roger J.
- Belhorn  Linda R.
- Benavides  Alfredo Gilberto Guerreros
- Beninati  Genevieve
- Benitez  Jorge A.
- Bennett  Annette R.
- Bennett  Elizabeth
- Beresnev  Tatiana
- Berman  Megan
- Bermudez  Maria I.
- Bernard  Marcia
- Bernstein  David I.
- Berry  Andrea
- Berry  Jennifer
- Berthaud  Vladimir
- Bialobok  Kristin
- Billings  Joanne L.
- Bittner  Zachary
- Blevins  Jeanne
- Blumenthal  Jill
- Boas  Rebecca
- Bocchini  Joseph
- Bold  Tyler D.
- Bondell  Alison
- Bondy  Paul
- Borger  Judith
- Borgetti  Scott
- Boscia  Joseph
- Boswell  Dean M.
- Bourgeois  Tana
- Bowers  Maggie
- Bradley  Paul S.
- Brady  Judith
- Brakema  Riemke
- Bran  Andres
- Branche  Angela R.
- Brandenburg  Boerries
- Brandon  Donald M.
- Bravo  Eric
- Briskin  Toby
- Broder  Gail
- Brosz  Adam B.
- Browder  David
- Browder  Lesley
- Brown  Cynthia
- Brown  Jeremy
- Brownlee  Robert
- Bruce  Elizabeth
- Bueno  Cynthia
- Bullock  Delia
- Bunce  Catherine A.
- Burch  Cortney
- Burgett  Michelle L.
- Burgher  Abram
- Butcher  Michael B.
- Buynak  Robert J.
- BĂ€cker  MartĂn
- Cade  LaShondra
- Calderon  Rafael
- Calderone  Richard
- Caldwell  Amy
- Calinescu  Cornell
- Call  Robert S.
- Callis  Jim
- Camacho-Gonzalez  Andres
- Campbell  Thomas B.
- Campbell  Wesley
- Cancilla  Michael
- Cannon  Kevin D.
- Cantos  Valeria D.
- Carmody  Ellie
- Carpenter  Christopher
- Carr  Melissa
- Carrascal  Monica B.
- Carsons  Steven E.
- Carvajal  Marianela
- Casey  Denise
- Caso  Jorge
- Castellino  Flora
- Castellon  Marvin
- Castro  Mario
- Catan  Hannah
- Cavert  Winston
- Chacón  Jorge A.
- Chadwick  Mesha M.
- Chamberlain  Amy
- Chan  Austin
- Chang  Jennifer
- Chebib  Mouna G.
- Chen  Corey M.
- Cheng  Margaret
- Cho  Iksung
- Choquette  Karin
- Chouteau  R. Michelle
- Chow  Brian D.W.
- Choza  Laura Julia Camacho
- Chrisley  Lisa
- Christensen  Shane G.
- Chu  Hanh
- Chu  Laurence
- Chughtai  Waseem
- Chung  Michael
- Ciambruschini  Annie
- Cicogna  Cristina
- Clarence B. Creech  I I
- Clark  Alexander
- Clark  Jesse L.
- Claybrook  Phillip
- Clement  Andrea
- Clement  Lauren
- Clemons  Steve
- Cohen  Lisa
- Cohen  Stuart H.
- Coleman  Jacob
- Colindres  Roberto A. Viau
- Connor  Joseph P.
- Conway  James H.
- Cooksey  Erin
- Coombs  Robert W.
- Cooney  Maureen
- Cooper  Deanna
- Coplan  Paul
- Corey  Lawrence
- Cornelison  Raymond
- Corral  Barbara
- Coslet  Jordan
- Coston  Erin
- Cotugno  Michael J.
- Cramer  Paul
- Cromer  Charnell
- Cross  Marshall A.
- Cruz-Valdez  Aurelio
- Curlin  Marcel
- Curry  LaKondria
- Custers  Jerome
- Cutz  Erika A.
- DallaPiazza  Michelle
- Dandachi  Dima
- Danford  Elizabeth
- Dang  Lyly
- Daniels  Stephen
- Davis  Joseph D.
- Davis  Matthew G.
- Davis  William B.
- Davis  Yvonne
- Davit  Rajesh K.
- de Groot  Anne Marit
- De La Cruz  Luis I.
- De La Matta Rodriguez  Claudia
- De Proost  Ian
- Dedon  Christopher
- Dedon  Jon F.
- Deese  Teresa
- Degan  Emily
- DeHaan  Elliot
- del Rio  Carlos
- Delgado  Ernesto
- Delgado  Michael
- Delgado  Mike
- Dellaero  David
- Denham  Douglas S.
- Desai  Chinar
- Desai  Parul
- Desjardins  Michael
- Deutsch  Karen
- Dever  Michael E.
- Devine  Naomi
- Dickey  Michelle
- Diemert  David J.
- Dietz  Craig
- Doblecki-Lewis  Susanne
- DomĂnguez  Sandra Janeth Ortega
- Dong  Jennifer L.
- Dora  Tambra
- Dorcely  Brenda
- Doust  Matthew W.
- Downing  Frances
- Dube  Michael P.
- Dubovsky  Filip
- Ducheneaux  Pete
- Duhart  Aeiress
- Duke  Elizabeth
- Dunbar  Debora
- Dunbar  Haoua
- Duncanson  Daniel
- Dunkle  Lisa M.
- Dunlevy  Hillary
- Duran  Adriana Sordo
- Dye  Amy
- Dyer  Carmel B.
- Dzigiel  Sarah
- DĂaz-Miralrio  Secia
- Easley  Mary
- Eaton  Niles
- Ebuh  Georgette
- Ebuh  Valentine M.
- Eckert  Lynn
- Eckhardt  Benjamin
- Eder  Frank S.
- Edupuganti  Srilatha
- Edward M. Tavel  Jr
- Edwards  Leslie A.
- Eickhoff  Mark
- El Sahly  Hana M.
- Ellerbeck  Edward
- Ellsworth  Grant
- Elnagar  Elwaleed
- Engler  Victoria
- Enright  Kendra
- Ensz  David J.
- Eppenbach  Sally
- Erickson  Sandra
- Eron  Joseph J.
- Escallon  Sebastian Garcia
- Esinhart  Tiffany
- Espinosa  Claudia
- Essink  Brandon J.
- Estrada  Denisse Alejandra Gonzålez
- Everette  Elizabeth
- Ewers  Evan C.
- Ewing  Beverly
- Falk  Amy
- Falsey  Ann R.
- Fas  Norberto
- Fay  Michael
- Fearon  Szheckera
- Feijoo  Brittany
- Feldman  Gregory J.
- Felsen  Uriel R.
- Fentanes  MarĂa JosĂ© Reyes
- Fichtenbaum  Carl
- Fiel  Tom
- Fierro  Carlos A.
- Finkelstein  Kenneth
- Finley  Jon
- Fiorillo  Suzanne
- Fitz-Patrick  David
- Florescu  Diana F.
- Flume  Patrick
- Fogarty  Charles M.
- Foley  Jennifer
- Follmann  Dean
- Folmar  Pink
- Folsom  Lyndsea
- Fong  Youyi
- Ford  Stacy
- Forero  Lina M.
- Forgosh  Les B.
- Formentini  Elizabeth
- Fouts  Rhodna
- Fragoso  Veronica G.
- Franco-Vitteri  Doris
- Frank  Ian
- Frederick Raiser  III
- Freeman  George H.
- Freese  Lena R.
- Freudemann  Karen
- Frey  Sharon E.
- Fried  David L.
- Friesen  Luke
- Fry  James
- Furey  Dawn
- Galloway  Christopher
- Galloway  Sarah
- Galvån  Jorge F. Méndez
- Garcia  Edgar
- Garcia  Jenina
- Garcia-Fragoso  Veronica
- GarcĂa  Iris
- Garvey  Janet
- Gay  Cynthia L.
- Gebhardt  Bruce C.
- Geiger  Grant
- Gelderblom  Huub G.
- George H. Bauer  Jr
- Geuss  Georgettea
- Ghadishah  Elham
- Gharib  Elie
- Gharib  Suzanne
- Gibson  Richard L.
- Gilbert  Peter B.
- Giorza  Juan Luis Yrivarren
- Gipson  Teletha
- Glenn  Gregory M.
- Goecker  Erin A.
- Goepfert  Paul A.
- Goldenberg  James N.
- Gomez  Blanca
- Gonzales-Zamora  Jose
- Gonzalez  Celia
- Gonzalez  Lazaro
- Gonzalez  Viviana
- Gonzålez  Luis H.
- Gordon  Bryan
- Gordon  Sarah
- Gorman  Richard
- Gottschlich  Gregory M.
- Gottschlich  Melissa
- Gower  Shanda
- Graciaa  Daniel S.
- Graham  Irene
- Grant  Amber
- Gray  Brett
- Gray  Glenda E.
- Gray  Roni
- Green  Allison
- Green  Sinikka L.
- Greene  Caroline
- Greene  Rusty
- Greninger  Alex
- Griffin  Carl P.
- Grillo  Joseph
- Grinsztejn  Beatriz
- Grossberg  Robert M.
- Grunstra  Bernard
- Guanira-Carranza  Juan V.
- Guarin  Laura Hernandez
- Guerrero  Laura Ruy Sanchez
- Guerrero  Sonia
- Guillory  Clint C.
- Guiney  Caitlin J.
- Guizar  Sharzhaad Molina
- Gular  Catherine Q.
- Gunaratne  Shauna H.
- Haber  Milton
- Hachigian  Greg
- Haggag  Amina Z.
- Hall  Evelyn
- Halpert  David
- Hamilton  Holli
- Hammershaimb  Elizabeth
- Han-Conrad  Laurie J.
- Harden  Kate
- Harmon  Esther L.
- Harper  Charles
- Harper  Wayne L.
- Harrell  Nicole
- Harrington  Hannah
- Harrison  Kristina
- Harrison  Tavane
- Harshell  Shana
- Hartman  William R.
- Hartvickson  Robyn
- Hatlen  Timothy J.
- Hauge  Kirsten
- Haughey  Lynne A.
- Haynes  Michelle
- Headden  Gary
- Healy  C. Mary
- Healy  Catherine Mary
- Hedges  Parke
- Heerwegh  Dirk
- Hegmann  Theresa
- Heimonen  Jessica
- Heinzig-Cartwright  Destiny S.
- Henderson  Jeffrey A.
- Henderson  Renea
- Henderson  Sheryl L.
- Hendriks  Jenny
- Hennekes  Gayle D.
- Hepburn  Matthew
- Herati  Ramin
- Herc  Erica
- Hernandez  Will
- HernĂĄndez  Alejandro QuintĂn Barrat
- Herrera  Vida Veronica Ruiz
- Hilder  Robin
- Hill  Janet
- Hill  John M.
- Hinojosa  Zindy YazmĂn ZĂĄrate
- Hirsch  Ian
- Ho  Ken
- Hoberman  Alejandro
- Hoft  Daniel
- Hojat  Leila
- Holdeman  Troy
- Hollister  Ripley R.
- Holloway  Lisa
- Holt  Gregory
- Hong  Matthew
- Hong  Rosamond
- Hong  Stephan
- Horn  Amanda
- Horton  Manisha
- Horwith  Gary
- Hosek  Sybil G.
- Hoseyni  Cyrus
- Howenstine  Patty
- Huang  Ying
- Huang  Yunda
- Huang  Yunda
- Huffine  Cory J.
- Huffine  Esther S.
- Hull  Christine
- Hurst  James W.
- Huskey  Shamika
- Hussain  Mary
- Hussey  Julie
- Hussey  Morgan
- Hutchens  Mark
- Hutchins  Tanya
- Hutter  Julia
- Huynh  Vincent
- Ibarra  Jessica
- Immergluck  Lilly
- Ince  Dilek
- Ingalsbe-Geno  Sarah M.
- Inniss  Asha
- Irani  Farah
- Israelsen  Ryan
- Iverson  Leslie
- Iwuala  Genevieve
- Jackson  Lisa A.
- Jackson-Booth  Peta-Gay
- Jacobs  Michael
- Jacobsen  Colleen
- Jacobson  Jeffrey M.
- Jacqmein  Jeffry
- Jaegle  Kate
- Jaffer  Shireen H.
- Jahromi  Maryam
- James  Frank
- Janes  Holly E.
- Jay  Melanie
- Jeanfreau  Robert
- Jeanfreau  Susan
- Jeffrey Dugas  Sr
- Jennings  William
- Jenson  Natasa
- Jerome  Keith R.
- John W. McGettigan  Jr
- Johnson  Danyel
- Johnson  Diane H.
- Johnson  Erica
- Johnson  Jennie
- Johnson  Jennifer A.
- Johnson  John
- Johnson  Kristen
- Johnson  Lisa
- Johnson  Maria
- Johnston  Carrie
- Jones  Kathleen S.
- Jones  William H.
- Jones-López  Edward C.
- Jordan  Bailey
- Joseph Eron  Jr
- Juraszek  Jarek
- Justman  Jessica E.
- Kahney  Scott
- Kalams  Spyros A.
- Kamidani  Satoshi
- Kandiah  Sheetal
- Kane  Pamela
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- Walker  Shannon
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- Walsh  Stephen R.
- Walsh  Stephen R.
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- Walters  Ayanna
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- Waters  Michael
- Watkins  Breanz
- Webb  Angella
- Webster  Hala
- Weidler  Jessica L.
- Weiss  Thomas
- Wells  Margaret
- Wendell Lewis  III
- Wendrow  Andrea
- Werne  Melody
- West  Whitney
- Whatley  Jordan L.
- Whitaker  Jennifer A.
- White  Jewel J.
- White  Julie
- White  Toni
- Wijewardane  Priyantha N.
- Wilkin  Timothy
- Wilkinson  Bethanie
- William S. Davis  Jr
- Williams  Barton G.
- Williams  Hayes
- Williams  Samantha
- Wilson  Christine
- Wilson  Clint
- Wilson  Greg
- Wilson  Natasha
- Winbigler  Jennifer
- Winkle  Peter J.
- Winokur  Patricia L.
- Witbeck  John
- Wohl  David
- Woo  Wayne
- Woodside  Leana
- Wortman  Glenn
- Wu  Yi H.
- Wylie  Paul E.
- Yang  Fan
- Yang  Kinara S.
- Yoon  Anelgine C.
- York  Jill
- Young  Cheryl
- Yu  Chenchen
- Yusin  Joseph
- Zapata  Luz
- Zash  Rebecca
- Zegarra  Eneyda Giuvanela Llerena
- Zemanek  Arthur L.
- Zenlea  Kate
- Zepeda  Karla
- Zervos  Marcus J.
- Zhai  Nan
- Zhang  Kevin
- Zhou  James
- Zimmer  Andrea
- Zingman  Barry S.
- Zorrilla  Carmen D.
- Ăñez  GermĂĄn
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/10/2023
- Field of study
Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7â15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05â0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01â0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health
Risk of COVID-19 after natural infection or vaccinationResearch in context
- Author
- A. Lina Rosengren
- Abram Burgher
- Adam B. Brosz
- Adam Rosen
- Adam Schwartz
- Adriana Sordo Duran
- Adrienna Marquez
- Adrienne E. Shapiro
- Aeiress Duhart
- Afsoon Roberts
- Albert Liu
- Alejandro Hoberman
- Alejandro QuintĂn Barrat HernĂĄndez
- Alex Greninger
- Alexander Clark
- Alfredo Gilberto Guerreros Benavides
- Alice McGarry
- Alicia Arrazcaeta
- Alisha Lutat
- Alison Bondell
- Alison Pellecchia
- Allie Oplinger
- Allison Green
- Allison O'Brien
- Alpa Patel
- Alyssa-Kay Peay
- Amanda Horn
- Amanda Lilienthal
- Amanda Occhino
- Amanda Philyaw
- Amaran Moodley
- Amber Grant
- Amber Stanford
- Amesika Nyaku
- Amie Shannon
- Amina Z. Haggag
- Amit Paliwal
- Amy Caldwell
- Amy Chamberlain
- Amy Dye
- Amy Falk
- Amy Kelley
- Amy Medina
- Amy Potts
- Amy Salzl
- Amy Sherman
- Amy Starr
- Amy Thompson
- Andrea Berry
- Andrea Clement
- Andrea Wendrow
- Andrea Zimmer
- Andres Bran
- Andres Camacho-Gonzalez
- Andrew Lauria
- Andrew McConnell
- Andrew McWilliams
- Anelgine C. Yoon
- Angela Lee
- Angela R. Branche
- Angelica Kottkamp
- Angella Webb
- Ann M. Milliken
- Ann R. Falsey
- Anna S. Lok
- Anna Wald
- Anne Marit de Groot
- Anne-Marie Rick
- Annette R. Bennett
- Annie Ciambruschini
- Annie Luetkemeyer
- Anthony Kim
- Anum Abbas
- Anyela Lara
- April Pixler
- Ariana C. Stanton
- Arthur L. Zemanek
- Asha Inniss
- Ashley Kennedy
- Ashley Perez
- Ashley Warden
- Asif Noor
- Atoya Adams
- Aurelio Cruz-Valdez
- Austin Chan
- Austin Swanson
- Ayanna Walters
- Ayoade Avworo
- Bailey Jordan
- Barbara Corral
- Barbara Rizzardi
- Barbara Rizzardi
- Barbara S. Taylor
- Barry S. Zingman
- Barton G. Williams
- Beatriz Grinsztejn
- Becky Martinez
- Ben Ladner
- Benjamin Eckhardt
- Benjamin J. Luft
- Bernard Grunstra
- Beth Safirstein
- Bethanie Wilkinson
- Beverly E. Sha
- Beverly Ewing
- Bindu Balani
- Blanca Gomez
- Bo Shopsin
- Boerries Brandenburg
- Brandie Taylor
- Brandon J. Essink
- Brandy Ball
- Breanz Watkins
- Brenda Dorcely
- Brendan Levy
- Brett Gray
- Brett Leav
- Brian D.W. Chow
- Brit Sovic
- Brittany Feijoo
- Brittany Stewart
- Bruce C. Gebhardt
- Bruce G. Rankin
- Bruce McClenathan
- Bruno Valenti
- Bryan Gordon
- C. Mary Healy
- Caitlin J. Guiney
- Caitlin Moran
- Candace Smith
- Candice Montros
- Carina A. Rodriguez
- Carl Fichtenbaum
- Carl P. Griffin
- Carlos A. Fierro
- Carlos del Rio
- Carlos Lopez
- Carlos Malvestutto
- Carmel B. Dyer
- Carmen A. Paez
- Carmen Amador
- Carmen D. Zorrilla
- Carmen Medina
- Carol Ann Linebarger
- Carol Kauffman
- Carol L. Mitchell
- Carolene Stephenson
- Caroline Greene
- Carolyn Scatamacchia
- Carolyn Tran
- Carrie Johnston
- Carrie Sopher
- Catherine A. Bunce
- Catherine Mary Healy
- Catherine Q. Gular
- Cathy Laflan
- Cecilia McKeown-Bragas
- Celia Gonzalez
- Celia Maxwell
- Charles Harper
- Charles M. Fogarty
- Charlotte-Paige Rolle
- Charnell Cromer
- Chelsea Miles
- Chelsie Nutsch
- Chelsie Nutsch
- Chen S. Tan
- Chenchen Yu
- Cheryl Nuss
- Cheryl Young
- Chimeremma Nnadi
- Chinar Desai
- Christian Tomaszewski
- Christina A. Rostad
- Christina Bacher
- Christina Kennelly
- Christine Akamine
- Christine B. Turley
- Christine Hull
- Christine Wilson
- Christopher Carpenter
- Christopher Dedon
- Christopher Galloway
- Christopher Matich
- Christy Schmeck
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- Timothy Wilkin
- Tina Tong
- Tina Wang
- Toby Briskin
- Todd Simmons
- Tom Fiel
- Toni Robinson
- Toni White
- Tracy Okonya
- Tracy R. Klein
- Trina L. Reynolds
- Troy Holdeman
- Tyler D. Bold
- Uriel R. Felsen
- Valentine M. Ebuh
- Valeria D. Cantos
- Valerie K. Arnold
- Vanessa Abad
- Vanessa Raabe
- Veronica G. Fragoso
- Veronica Garcia-Fragoso
- Veronica Procasky
- Veronica Viar
- Vicki E. Miller
- Vickie Leathers
- Victoria Andriulis
- Victoria Engler
- Victoria Mosteller
- Victoria R. Anderson
- Vida Veronica Ruiz Herrera
- Vincent Huynh
- Vincent Mirkil
- Vivek Rajasekhar
- Viviana Gonzalez
- Vladimir Berthaud
- Walter Patton
- Wanda Ramon
- Waseem Chughtai
- Wayne L. Harper
- Wayne Woo
- Wendell Lewis
- Wendell Lewis III
- Wendy A. Keitel
- Wesley Campbell
- Wesley Van Ever
- Westly Keating
- Whitney West
- Will Hernandez
- William B. Davis
- William B. Smith
- William H. Jones
- William Jennings
- William Kirby
- William P. Silver
- William R. Hartman
- William S. Davis Jr.
- William Schnitz
- William Seger
- Winniberg Stephany Alvarez LeĂłn
- Winston Cavert
- Xiaomi Tong
- Yaa D. Oppong
- Yi H. Wu
- Ying Huang
- Yogesh K. Paliwal
- Youyi Fong
- Yunda Huang
- Yunda Huang
- Yvonne Davis
- Zachary Bittner
- Zainab Rizvi
- Zindy YazmĂn ZĂĄrate Hinojosa
- Zudi-Mwak Takizala
- Publication venue
- Elsevier
- Publication date
- 01/10/2023
- Field of study
Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7â15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05â0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01â0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health
Subretinal Hyperreflective Material in the Comparison of Age-Related Macular Degeneration Treatments Trials
- Author
- A. Tom Ghuman
- Aaron Towe
- Abby Brotherton
- Adam Brooks
- Adam Specker
- Adam Zamboni
- Adrienne Brower-Lingsch
- Aida Ayyad
- Alan Letson
- Alan Margherio
- Alan Ruby
- Albert Edwards
- Albert Frederick
- Alecia Travis
- Alessandro Castellarin
- Alex S. Willoughby
- Alex Schlosser
- Alexander Ho
- Alexander Khvatov
- Alexander Melamud
- Allen Ho
- Allison Cassidy
- Allison Guidry
- Allison Schnader
- Alysia Cronise
- Amanda Barnett
- Amanda Battcher
- Amanda Butt
- Amanda Bye
- Amanda Dinatale
- Amanda Fec
- Amanda Milliron
- Amanda Palomo
- Ames Munden
- Amy Dilback
- Amy Harris
- Amy Leviton
- Amy Martir
- Amy Noffke
- Amy Schultz
- Andreas Lauer
- Andrew Barkmeier
- Andrew N. Antoszyk
- Angela Price
- Angela Wealti
- Angie Karow
- Ann Arnold
- Ann Borthwick
- Ann Lundquist
- Anna Fagan
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- Franklin G. Miller
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- Gabe Balea
- Gary Brown
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- Gene Knutson
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- Glenda Salcedo
- Glenn J. Jaffe
- Glenn Jaffe
- Glenn Jaffe
- Glenn Jaffe
- Glenn Wing
- Greg K. Whittington
- Gregg Greanoff
- Grunwald
- Gui-shuang Ying
- Gui-Shuang Ying
- Guy Somers
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- Hayashi
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- Jaffe
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- Jennifer Banks
- Jennifer Belz
- Jennifer Frederick
- Jennifer Grillion-Cerone
- Jennifer Krumlauf
- Jennifer M. Rose
- Jennifer Mindel
- Jennifer Savage
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- Jennifer Walsh
- Jenny Wolfe
- Jeri Perry
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- Jessica Basefsky
- Jessica Gaultney
- Jessica Miner
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- Jiayan Huang
- Jill A. Salerno
- Jill Johnson
- Joan DuPont
- Joan Overend
- Joan Videtich
- JoAnn Starr
- Jodi Creighton
- Joe Logan
- Joel A. Pearlman
- John Bucci
- John Choong
- John Christoforidis
- John Davies
- John DuBois
- John Head
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- John Martin
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- John Snater
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- John Wells
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- JoLene G. Carranza
- Jonathan McCue
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- Joseph Coney
- Joseph Googe
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- Joseph M. Civantos
- Joseph Maguire
- Joseph P. Walker
- Joseph Rossi
- Joy Elliott
- Joyce W. Bryant
- Juan E. Grunwald
- Juan E. Grunwald
- Juan E. Grunwald
- Juan E. Grunwald
- Juan Romero
- Judith Alexander
- Judith Hall
- Judy Brower
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- Julia Monsonego
- Julia Wray
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- Julio Sierra
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- Justin Smith
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- Karen Duignan
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- Kelly West
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- Kim Bell
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- Kimberly Welch
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- Kristina Oliver
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- Lacy Palazzotta
- LaDetrick Oliver
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- Maureen G. Maguire
- Maureen G. Maguire
- Maureen G. Maguire
- Maureen G. Maguire
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- Michele Connaughton
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- Mike Jones
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- Mitchell Fineman
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- Nancy Gore
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- Nyla Secor
- Odette Houghton
- P. Kumar Rao
- Pam Miller
- Pamela Rath
- Pamela Rieves
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- Patricia Bradley
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- Patrick Williams
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- Peggy Gilbert
- Peggy Miller
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- Peter Sonkin
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- Peter Steinkamp
- Philip J. Ferrone
- Piccolino
- Polly Quiram
- Pravin Dugel
- Prithvi Mruthyunjaya
- Rachel Arnott
- Rachel Pierce
- Raj Maturi
- Ramin Sarrafizadeh
- Randy Verdick
- Raymond Iezzi
- Raymond Sjaarda
- Razmig Babikian
- Reagan H. Bradford
- Rebecca Fitzgerald
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- Reginald Sanders
- Reid Schindler
- Reina Yebra
- Rhonda Waldron
- Rhonda Weeks
- Richard A. Garfinkel
- Richard F. Dreyer
- Richard Fish
- Richard Grodin
- Richard Kaiser
- Rick Isernhagen
- Ristau
- Rita Veksler
- Rob Richmond
- Robbin Spivey
- Robert Bergren
- Robert Equi
- Robert Frantz
- Robert L. Avery
- Robert L. Avery
- Robert Mittra
- Robert Myles
- Robert N. Johnson
- Robert Ramsay
- Robert See
- Robert Wang
- Robert Wendel
- Robin Mitchell
- Robin Ty
- Rohana Yager
- Ronald Glatzer
- Ronald Kingsley
- RonaLyn Esquejo-Leon
- Ronnie Tomany
- Rosa Rodriguez
- Rosenfeld
- Roy Ann Moore
- Roy Trent Wallace
- Ruchira Glaser
- Russ Burris
- Russell Burns
- Russell E. Burns
- Ryan Neist
- Ryan Shultz
- Saba Mukarram
- Sally Arceneaux
- Sandra Arenas
- Sandra Harkins
- Sandra Reed
- Sandra Sall
- Sandra Stinnett
- Sandy Chong
- Sandy Lash
- Sandy Lewis
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- Sara Crowell
- Sara Downs
- Sarah Brett
- Sarah Buckley
- Sarah Ennis
- Sarah Gach
- Sarah Hines
- Sarah Jones
- Sarah Mobley
- Sarah Nolte
- Sarah Oelrich
- Sarah Pachman
- Sarah Risard
- Sarita Scott
- Sashi Kaur
- Saxena
- Scheleen Dickens
- Scott Pendergast
- Scott Pickell
- Scott Savage
- Scott Sneed
- Sean Grout
- Sepideh Hami
- Serena Neal
- Shamekia Newton
- Shannon Goddard
- Shannon Howard
- Shannya Townsend-Patrick
- Shantia Shears
- Sharon Fekrat
- Shashi Kini
- Shawnique Latham
- Shayla Hay
- Sheila Smith-Brewer
- Shelly Olson
- Shelly Valardi
- Sheri Carbon
- Shirley Ira
- Silvia Linares
- Sohail Hasan
- Solomon
- Sonny Icks
- Sophia Griffin
- Sophie J. Bakri
- Sophie J. Bakri
- Srilaxmi Bearelly
- Stacey Andelman
- Stacy McGilvra
- Starr Muscle
- Stefani Karakas
- Stephanie Morrow
- Stephanie Schindeldecker
- Stephen Couvillion
- Stephen Fransen
- Stephen Hobbs
- Stephen L. Perkins
- Stephen Petty
- Stephen Russell
- Stephen Shelley
- Stephen Young
- Steve Bennett
- Steven Bailey
- Steven Bennett
- Steven Leff
- Steven Schremp
- Stuart Green
- Stuart L. Fine
- Stuart L. Fine
- Stuart L. Fine
- Sujatha Subramaniam
- Sundeep Dev
- Sunil Srivastava
- Sunir Garg
- Suresh R. Chandra
- Susan B. Bressler
- Susan Brown
- Susan K. Nolte
- Susan K. Nolte
- Susan K. Nolte
- Susan Pope
- Susan Rath
- Susan Ryan
- Susanna S. Park
- Susannah Held
- Susie Chang
- Svetlana Reznichenko
- T. Michael Nork
- Tammy Butcher
- Tammy Ressel
- Taneika Howard
- Tanya Marsh
- Tarek Hassan
- Teresa Coffey
- Teresa Liesegang
- Terri Kidd
- Terry Hawks
- Thea Tantum
- Theodossiadis
- Theresa Cain
- Theresa Jeffers
- Thomas A. Ciulla
- Thomas Aaberg
- Thomas Hwang
- Thomas Link
- Thomas Stevens
- Thomas W. Stone
- Tien Wong
- Tiffany Guerrero
- Tiffany Swinford
- Tim Wright
- Timothy Crew
- Timothy Olsen
- Tina Bell
- Tina Bell
- Tina Cleary
- Tina T. Higdon
- Todd Blevins
- Todd Petrin
- Tom Shannon
- Tom Steele
- Tony Tsai
- Tonya Harrington
- Tori Jones
- Torsten Wiegand
- Tracey Brady
- Tracy Aly
- Tracy Grooten
- Travis A. Meredith
- Travis A. Meredith
- Trenise Steele
- Trexler M. Topping
- Troy Kieser
- Uma Balasubramaniam
- Ursula Lord
- Valerie Kirschner
- Valerie Lazarte
- Vanessa Bergman
- Vanessa Denny
- Vasanti Sookhai
- Veronica Sneed
- Vicky Seitz
- Virginia R. Regan
- Vivian Tanner
- W. Lloyd Clark
- Wanda Heath
- Wayne Solley
- Willia Ingram
- William Carli
- William Gilbert
- William Snyder
- William Wood
- Witmer
- Yesmin Urias
- Ying
- Publication venue
- 'Elsevier BV'
- Publication date
- Field of study