Carrie L Lucas, PhD
Research & Publications
Biography
News
Research Summary
The Lucas lab advances basic and translational immunology through discovery and mechanistic investigation of severe, human immunodeficiency and autoinflammatory disorders, often caused by single-gene defects. Starting with patients and extending to mouse models, our work aims to dive deeply into fundamental yet translationally relevant biology of adaptive and innate immune cells by combining genetic, cellular, molecular, and in-vivo approaches. We then aim to apply this knowledge not only to devise targeted therapies for rare disorders but also to more generally illuminate approaches to improve common diseases with shared features of underlying pathophysiology. Major current efforts in the lab focus on genetic errors of immunity from phosphoinositide 3-kinase (PI3K) mutations, ELF4 transcription factor mutations, and others in the research pipeline.
Coauthors
Research Interests
Immunologic Deficiency Syndromes; Immunoproliferative Disorders; Inflammation; T-Lymphocytes; Signal Transduction; Hereditary Autoinflammatory Diseases
Selected Publications
- Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine-associated myocarditis.Barmada A, Klein J, Ramaswamy A, Brodsky NN, Jaycox JR, Sheikha H, Jones KM, Habet V, Campbell M, Sumida TS, Kontorovich A, Bogunovic D, Oliveira CR, Steele J, Hall EK, Pena-Hernandez M, Monteiro V, Lucas C, Ring AM, Omer SB, Iwasaki A, Yildirim I, Lucas CL. Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine-associated myocarditis. Sci Immunol 2023, 8: eadh3455. PMID: 37146127, DOI: 10.1126/sciimmunol.adh3455.
- The role of PI3Kγ in the immune system: new insights and translational implicationsLanahan SM, Wymann MP, Lucas CL. The role of PI3Kγ in the immune system: new insights and translational implications Nature Reviews Immunology 2022, 22: 687-700. PMID: 35322259, PMCID: PMC9922156, DOI: 10.1038/s41577-022-00701-8.
- Human autoinflammatory disease reveals ELF4 as a transcriptional regulator of inflammationTyler PM, Bucklin ML, Zhao M, Maher TJ, Rice AJ, Ji W, Warner N, Pan J, Morotti R, McCarthy P, Griffiths A, van Rossum AMC, Hollink IHIM, Dalm VASH, Catanzaro J, Lakhani SA, Muise AM, Lucas CL. Human autoinflammatory disease reveals ELF4 as a transcriptional regulator of inflammation Nature Immunology 2021, 22: 1118-1126. PMID: 34326534, PMCID: PMC8985851, DOI: 10.1038/s41590-021-00984-4.
- Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in childrenRamaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, Lucas CL. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children Immunity 2021, 54: 1083-1095.e7. PMID: 33891889, PMCID: PMC8043654, DOI: 10.1016/j.immuni.2021.04.003.
- Human PI3Kγ deficiency and its microbiota-dependent mouse model reveal immunodeficiency and tissue immunopathologyTakeda AJ, Maher TJ, Zhang Y, Lanahan SM, Bucklin ML, Compton SR, Tyler PM, Comrie WA, Matsuda M, Olivier KN, Pittaluga S, McElwee JJ, Long Priel DA, Kuhns DB, Williams RL, Mustillo PJ, Wymann MP, Koneti Rao V, Lucas CL. Human PI3Kγ deficiency and its microbiota-dependent mouse model reveal immunodeficiency and tissue immunopathology Nature Communications 2019, 10: 4364. PMID: 31554793, PMCID: PMC6761123, DOI: 10.1038/s41467-019-12311-5.
- Infections in activated PI3K delta syndrome (APDS)Brodsky NN, Lucas CL. Infections in activated PI3K delta syndrome (APDS) Current Opinion In Immunology 2021, 72: 146-157. PMID: 34052541, DOI: 10.1016/j.coi.2021.04.010.
- SARS-CoV-2–related MIS-C: A key to the viral and genetic causes of Kawasaki disease?Sancho-Shimizu V, Brodin P, Cobat A, Biggs CM, Toubiana J, Lucas CL, Henrickson SE, Belot A, Haddad E, Beland K, Pujol A, Schlüter A, Planas-Serra L, Aguilera-Albesa S, Valencia-Ramos J, Rodríguez-Palmero A, Gut M, Rivière J, Colobran R, Soler-Palacin P, Rodriguez-Gallego C, De Diego R, Flores C, Alsina L, Blazquez-Gamero D, Jordan I, Keles S, Emiroglu M, Akcan O, Alkan G, Aytekin S, Gul Y, Öz Ş, Bozdemir S, Bayhan G, Yüksek S, Parlakay A, Gülhan B, Yahşi A, Kilic A, Karbuz A, Erdeniz E, Özkan E, Orbak Z, Aydemir Ş, Celik J, Kandemir B, Aytekin G, Kapakli H, Yarar V, Yosunkaya A, Vatansev H, Aytekin C, Torun S, Nepesov S, Coskuner T, Sözeri B, Demirkol Y, Kasapcopur O, Yıldız M, Sevketoglu E, Hatipoğlu N, Özçelik T, Yesilbas O, Aydin Z, Sediva A, Klocperk A, Bloomfield M, Meyts I, Delafontaine S, Haerynck F, Hoste L, Shahrooei M, Marque L, Neves J, Novelli G, Novelli A, Aiuti A, Casari G, Bousfiha A, Almuhsen S, Sobh A, Gagro A, Bajolle F, Bonnet D, Lebon P, Lei W, Lee D, Seeleuthner Y, Zhang P, Maglorius M, Philippot Q, Pelham S, Bastard P, Zhang Q, Jouanguy E, Puel A, Herberg J, Kuijpers T, Bellos E, Kaforou M, Menikou S, Pan-Hammarström Q, Hammarström L, Abolhassani H, Bryceson Y, Condino-Neto A, Prando C, Bando S, Cavalcanti A, Fellay J, Blanchard-Rohner G, Mansouri D, Mahmoudi S, Boyarchuk O, Volokha A, Bondarenko A, Stepanovskiy Y, Mogensen T, van de Beek D, Andreakos E, Papadaki M, Tayoun A, Halwani R, Al-Mulla F, Franco J, Lau Y, Kwan M, Imai K, Okada S, Bolze A, Butte M, Hsieh E, Drolet B, Arkin L, Itan Y, Maniatis T, Arditi M, Cooper M, Schmitt E, Chakravorty S, Anderson M, Su H, Notarangelo L, Tangye S, Milner J, Levin M, Abel L, Bogunovic D, Casanova J, Zhang S. SARS-CoV-2–related MIS-C: A key to the viral and genetic causes of Kawasaki disease? Journal Of Experimental Medicine 2021, 218: e20210446. PMID: 33904890, PMCID: PMC8080850, DOI: 10.1084/jem.20210446.
- Uncontrolled Epstein-Barr Virus as an Atypical Presentation of Deficiency in ADA2 (DADA2)Brooks JP, Rice AJ, Ji W, Lanahan SM, Konstantino M, Dara J, Hershfield MS, Cruickshank A, Dokmeci E, Lakhani S, Lucas CL. Uncontrolled Epstein-Barr Virus as an Atypical Presentation of Deficiency in ADA2 (DADA2) Journal Of Clinical Immunology 2021, 41: 680-683. PMID: 33394316, DOI: 10.1007/s10875-020-00940-1.
- Editorial: Human Disorders of PI3K BiologyLucas CL, Tangye SG. Editorial: Human Disorders of PI3K Biology Frontiers In Immunology 2020, 11: 617464. PMID: 33329612, PMCID: PMC7732539, DOI: 10.3389/fimmu.2020.617464.
- The mystery of MIS-C post-SARS-CoV-2 infectionBrodsky NN, Ramaswamy A, Lucas CL. The mystery of MIS-C post-SARS-CoV-2 infection Trends In Microbiology 2020, 28: 956-958. PMID: 33190685, PMCID: PMC7556780, DOI: 10.1016/j.tim.2020.10.004.
- Novel compound heterozygous variants in NHLRC2 in a patient with FINCA syndromeBrodsky NN, Boyarchuk O, Kovalchuk T, Hariyan T, Rice A, Ji W, Khokha M, Lakhani S, Lucas CL. Novel compound heterozygous variants in NHLRC2 in a patient with FINCA syndrome Journal Of Human Genetics 2020, 65: 911-915. PMID: 32435055, DOI: 10.1038/s10038-020-0776-0.
- Epstein–Barr Virus Susceptibility in Activated PI3Kδ Syndrome (APDS) ImmunodeficiencyCarpier JM, Lucas CL. Epstein–Barr Virus Susceptibility in Activated PI3Kδ Syndrome (APDS) Immunodeficiency Frontiers In Immunology 2018, 8: 2005. PMID: 29387064, PMCID: PMC5776011, DOI: 10.3389/fimmu.2017.02005.
- Effective "activated PI3Kδ syndrome"-targeted therapy with the PI3Kδ inhibitor leniolisib.Rao VK, Webster S, Dalm VASH, Šedivá A, van Hagen PM, Holland S, Rosenzweig SD, Christ AD, Sloth B, Cabanski M, Joshi AD, de Buck S, Doucet J, Guerini D, Kalis C, Pylvaenaeinen I, Soldermann N, Kashyap A, Uzel G, Lenardo MJ, Patel DD, Lucas CL, Burkhart C. Effective "activated PI3Kδ syndrome"-targeted therapy with the PI3Kδ inhibitor leniolisib. Blood 2017, 130: 2307-2316. PMID: 28972011, PMCID: PMC5701526, DOI: 10.1182/blood-2017-08-801191.
- Novel PIK3CD mutations affecting N-terminal residues of p110δ cause activated PI3Kδ syndrome (APDS) in humansTakeda AJ, Zhang Y, Dornan GL, Siempelkamp BD, Jenkins ML, Matthews HF, McElwee JJ, Bi W, Seeborg FO, Su HC, Burke JE, Lucas CL. Novel PIK3CD mutations affecting N-terminal residues of p110δ cause activated PI3Kδ syndrome (APDS) in humans Journal Of Allergy And Clinical Immunology 2017, 140: 1152-1156.e10. PMID: 28414062, PMCID: PMC5632585, DOI: 10.1016/j.jaci.2017.03.026.
- Conformational disruption of PI3Kδ regulation by immunodeficiency mutations in PIK3CD and PIK3R1Dornan GL, Siempelkamp BD, Jenkins ML, Vadas O, Lucas CL, Burke JE. Conformational disruption of PI3Kδ regulation by immunodeficiency mutations in PIK3CD and PIK3R1 Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 1982-1987. PMID: 28167755, PMCID: PMC5338455, DOI: 10.1073/pnas.1617244114.
- PI3Kδ and primary immunodeficienciesLucas CL, Chandra A, Nejentsev S, Condliffe AM, Okkenhaug K. PI3Kδ and primary immunodeficiencies Nature Reviews Immunology 2016, 16: 702-714. PMID: 27616589, PMCID: PMC5291318, DOI: 10.1038/nri.2016.93.
- Genomics of Immune Diseases and New TherapiesLenardo M, Lo B, Lucas CL. Genomics of Immune Diseases and New Therapies Annual Review Of Immunology 2015, 34: 1-29. PMID: 26735698, PMCID: PMC5736009, DOI: 10.1146/annurev-immunol-041015-055620.
- Identifying genetic determinants of autoimmunity and immune dysregulationLucas CL, Lenardo MJ. Identifying genetic determinants of autoimmunity and immune dysregulation Current Opinion In Immunology 2015, 37: 28-33. PMID: 26433354, PMCID: PMC5583726, DOI: 10.1016/j.coi.2015.09.001.
- Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3KLucas CL, Zhang Y, Venida A, Wang Y, Hughes J, McElwee J, Butrick M, Matthews H, Price S, Biancalana M, Wang X, Richards M, Pozos T, Barlan I, Ozen A, Rao VK, Su HC, Lenardo MJ. Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K Journal Of Experimental Medicine 2014, 211: 2537-2547. PMID: 25488983, PMCID: PMC4267241, DOI: 10.1084/jem.20141759.
- Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiencyLucas CL, Kuehn HS, Zhao F, Niemela JE, Deenick EK, Palendira U, Avery DT, Moens L, Cannons JL, Biancalana M, Stoddard J, Ouyang W, Frucht DM, Rao VK, Atkinson TP, Agharahimi A, Hussey AA, Folio LR, Olivier KN, Fleisher TA, Pittaluga S, Holland SM, Cohen JI, Oliveira JB, Tangye SG, Schwartzberg PL, Lenardo MJ, Uzel G. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency Nature Immunology 2013, 15: 88-97. PMID: 24165795, PMCID: PMC4209962, DOI: 10.1038/ni.2771.
- Mg2+ Regulates Cytotoxic Functions of NK and CD8 T Cells in Chronic EBV Infection Through NKG2DChaigne-Delalande B, Li FY, O’Connor G, Lukacs MJ, Jiang P, Zheng L, Shatzer A, Biancalana M, Pittaluga S, Matthews HF, Jancel TJ, Bleesing JJ, Marsh RA, Kuijpers TW, Nichols KE, Lucas CL, Nagpal S, Mehmet H, Su HC, Cohen JI, Uzel G, Lenardo MJ. Mg2+ Regulates Cytotoxic Functions of NK and CD8 T Cells in Chronic EBV Infection Through NKG2D Science 2013, 341: 186-191. PMID: 23846901, PMCID: PMC3894782, DOI: 10.1126/science.1240094.
- LAG-3, TGF-β, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40LLucas CL, Workman CJ, Beyaz S, LoCascio S, Zhao G, Vignali DA, Sykes M. LAG-3, TGF-β, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40L Blood 2011, 117: 5532-5540. PMID: 21422469, PMCID: PMC3109721, DOI: 10.1182/blood-2010-11-318675.
- A CD8 T cell–intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivoFehr T, Lucas CL, Kurtz J, Onoe T, Zhao G, Hogan T, Vallot C, Rao A, Sykes M. A CD8 T cell–intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo Blood 2009, 115: 1280-1287. PMID: 20007805, PMCID: PMC2826238, DOI: 10.1182/blood-2009-07-230680.
- Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway.Haspot F, Fehr T, Gibbons C, Zhao G, Hogan T, Honjo T, Freeman GJ, Sykes M. Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway. Blood 2008, 112: 2149-55. PMID: 18577709, PMCID: PMC2518911, DOI: 10.1182/blood-2007-12-127449.
- Manipulating the immune system for anti-tumor responses and transplant tolerance via mixed hematopoietic chimerism.Gibbons C, Sykes M. Manipulating the immune system for anti-tumor responses and transplant tolerance via mixed hematopoietic chimerism. Immunological Reviews 2008, 223: 334-60. PMID: 18613846, PMCID: PMC2680695, DOI: 10.1111/j.1600-065X.2008.00636.x.
Clinical Trials
Conditions | Study Title |
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Children's Health; Genetics - Pediatric | Pediatric Genomics Discovery Program (PGDP) |