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INFORMATION FOR

Liza Konnikova, MD/PhD

Assistant Professor

Contact Information

Liza Konnikova, MD/PhD

Research Summary

Dr. Konnikova is a Neonatologist who focuses on the development of neonatal immunity at barrier sites such as the GI tract and the maternal-fetal interface and how this is regulated by the microbiome and the associated metabolome. Her group further studies the pathogenesis of diverse diseases such as sepsis, preterm labor, necrotizing enterocolitis (NEC), very early onset (VEO) and pediatric IBD.

Extensive Research Description

Dr. Konnikova is an Attending Neonatologist, Mucosal Immunologist, and an Assistant Professor in Pediatrics and Obstetrics, Gynecology, and Reproductive Sciences. She is also a member of the Human and Translational Immunology Program and Program in Translational Biomedicine at the Yale School of Medicine. Her focus is on developing immunity at mucosal surfaces and its role in the pathogenesis of diverse diseases such as necrotizing enterocolitis (NEC), pediatric inflammatory bowel disease (IBD), sepsis, and preterm labor.

Using a systems biology approach and cutting-edge techniques such as imaging and suspension mass cytometry and single cell RNA sequencing, her group is currently focused on improving our understanding of how mucosal immunity develops at barrier sites such as the GI tract and the maternal-fetal interface and what goes awry to cause disease. To this end, she has established a large biorepository (over 5,000 samples) of control and disease cryopreserved intestinal and placental tissue. Using tissue from her biobank, her group have been able to study the development of human fetal intestinal immunity (Stras et al., Developmental Cell, 2019). In their pursuit to understand the source of antigens priming in utero T cells, the have established numeroud collaborations to study fetal intestinal microbiome and metabolome and were the first to show that human fetal intestinal tissue contains abundant and diverse bacterial metabolites in the absence of a detectable microbiome (Li and Toothaker et al, JCI Insight, 2020). Her group is also studying the development of enterocytes (Ergozi et al., Nature Medicine, 2021) where they have recently identified insulin-secreting enteroendocrine cells in the small fetal intestine with broad implications for gut development, immune regulation, and diabetes treatment.

Additionally, using a large cohort of over 100 patients with IBD, she has been able to characterize immune signatures differentiating ulcerative colitis and Crohn's disease (Mitsialis et al., Gastroenterology, 2020). Moreover, her group has identified unique immune populations in NEC (Olaloye et al., JEM, 2021). Finally, in the pursuit to better understand the contribution of fetal immunity to placental homeostasis, using a non-human primate model, her group has shown that fetal cells contribute to intra-amniotic inflammation (Toothaker et al., Frontiers, 2020). Similarly, her group has characterized the diverse immune-landscape of second trimester human placentas including fetal memory T cells (Development, 2022).

Coauthors

Research Interests

Infant Nutrition Disorders; Infant, Premature; Placenta; Inflammatory Bowel Diseases; Immunity, Mucosal; Enterocolitis, Necrotizing; Gastrointestinal Microbiome

Selected Publications

  • Insulin is expressed by enteroendocrine cells during human fetal developmentA E, D L, BT M, K B, L F, X A, F W, K C, L K, S I. Insulin is expressed by enteroendocrine cells during human fetal development 2022 DOI: 10.1530/ey.19.10.8.
  • 524: PATHOGENIC RIPK1 MUTATIONS CAUSE INFANTILE-ONSET IBD WITH INFLAMMATORY AND FISTULIZING FEATURESSultan M, Wilschanski M, Millman P, McCourt B, Kol N, Lev A, Matar M, Barel O, Shamir R, Konnikova L, Somech R, Shouval D. 524: PATHOGENIC RIPK1 MUTATIONS CAUSE INFANTILE-ONSET IBD WITH INFLAMMATORY AND FISTULIZING FEATURES Gastroenterology 2022, 162: s-121-s-122. DOI: 10.1016/s0016-5085(22)60296-8.
  • DOP64 Pathogenic RIPK1 Mutations Cause Infantile-onset IBD with Inflammatory and Fistulizing FeaturesSultan M, Millman P, McCourt B, Kol N, Lev A, Matar M, Barel O, Shamir R, Wilschanski M, Konnikova L, Somech R, Shouval D. DOP64 Pathogenic RIPK1 Mutations Cause Infantile-onset IBD with Inflammatory and Fistulizing Features Journal Of Crohn's And Colitis 2022, 16: i109-i109. DOI: 10.1093/ecco-jcc/jjab232.103.
  • Su1867 BIG DATA ANALYTICS DEMONSTRATE A NOVEL, UNEXPECTED ASSOCIATION OF LOW SERUM IGG4 ANTIBODIES WITH INCREASED DISEASE SEVERITY IN 20% OF IBD PATIENTSKoutroumpakis F, Phillips A, Yadav D, Ahsan M, Rivers C, Machicado J, Tan X, Proksell S, Johnston E, Dueker J, Din H, Jana H, Tang G, Babichenko D, Barrie A, Hartman D, Konnikova L, Dunn M, Binion D. Su1867 BIG DATA ANALYTICS DEMONSTRATE A NOVEL, UNEXPECTED ASSOCIATION OF LOW SERUM IGG4 ANTIBODIES WITH INCREASED DISEASE SEVERITY IN 20% OF IBD PATIENTS Gastroenterology 2020, 158: s-681-s-682. DOI: 10.1016/s0016-5085(20)32394-5.
  • 317 CYTOF ANALYSIS OF HUMAN COLON AND BLOOD REVEALS DISTINCT IMMUNE SIGNATURES OF ULCERATIVE COLITIS AND CROHN'S DISEASEMitsialis V, Wall S, Liu P, Ordovas-Montanes J, Parmet T, Field M, McCourt C, Toothaker J, Goldsmith J, Kean L, Shalek A, Tseng G, Konnikova L, Snapper S. 317 CYTOF ANALYSIS OF HUMAN COLON AND BLOOD REVEALS DISTINCT IMMUNE SIGNATURES OF ULCERATIVE COLITIS AND CROHN'S DISEASE Gastroenterology 2020, 158: s-57. DOI: 10.1016/s0016-5085(20)30824-6.
  • 1240 Increased Mucosal Innate Immune Activation in Hereditary Alpha Trytpasemia Subjects Is Predictive of Clinical Response to Tofacitanib TherapyGlover S, Davis E, Shirley J, Konnikova L. 1240 Increased Mucosal Innate Immune Activation in Hereditary Alpha Trytpasemia Subjects Is Predictive of Clinical Response to Tofacitanib Therapy The American Journal Of Gastroenterology 2019, 114: s691-s692. DOI: 10.14309/01.ajg.0000594488.99132.5d.
  • Tu1845 – Identification of a Unique Population of Gi Mast Cells in a Subset of Patients with Mast Cell Activation SyndromeHamilton M, Konnikova L, Pozdnyakova O, Lyons J, Milner J, Shirley J, Ryan L, Tang Y, Snapper S, Glover S. Tu1845 – Identification of a Unique Population of Gi Mast Cells in a Subset of Patients with Mast Cell Activation Syndrome Gastroenterology 2019, 156: s-1146. DOI: 10.1016/s0016-5085(19)39831-2.
  • 947 – Priming and Maturation of the Human Fetal Immunity Occurs Early in Fetal DevelopmentStras S, Werner L, Toothaker J, Shouval D, Konnikova L. 947 – Priming and Maturation of the Human Fetal Immunity Occurs Early in Fetal Development Gastroenterology 2019, 156: s-202. DOI: 10.1016/s0016-5085(19)37297-x.
  • Su1885 – Analysis of Human Colonic Tissue and Peripheral Blood by Mass Cytometry Reveals Immune Signatures Differentiating Inflammatory States in Uc, Cd, and ControlsMitsialis V, Wall S, Parmet T, Bousvaros A, Korzenik J, Snapper S, Konnikova L. Su1885 – Analysis of Human Colonic Tissue and Peripheral Blood by Mass Cytometry Reveals Immune Signatures Differentiating Inflammatory States in Uc, Cd, and Controls Gastroenterology 2019, 156: s-648-s-649. DOI: 10.1016/s0016-5085(19)38522-1.
  • Su1884 – Combined Rnaseq and Cytof Analysis of Pbmcs Reveal Unique Profiles Between Il10 Receptor Deficiency and IBD Patients and Non-Ibd ControlsLiu P, Mitsialis V, Wall S, Shouval D, Gordon W, Snapper S, Konnikova L. Su1884 – Combined Rnaseq and Cytof Analysis of Pbmcs Reveal Unique Profiles Between Il10 Receptor Deficiency and IBD Patients and Non-Ibd Controls Gastroenterology 2019, 156: s-648. DOI: 10.1016/s0016-5085(19)38521-x.
  • CD117+ Exosomes and Mast Cells From Hereditary Alpha Tryptasemia Patients Reveal Unique Phosphorylation, Lipidomics, and Proteomics Profiles: Category Award (Small Intestine): Presidential Poster AwardAlli A, Konnikova L, Tuna K, Denslow N, Nouri M, Koh J, Li J, Tang Y, Shirley F, Ryan L, Lyons J, Milner J, Snapper S, Glover S. CD117+ Exosomes and Mast Cells From Hereditary Alpha Tryptasemia Patients Reveal Unique Phosphorylation, Lipidomics, and Proteomics Profiles: Category Award (Small Intestine): Presidential Poster Award The American Journal Of Gastroenterology 2018, 113: s668. DOI: 10.14309/00000434-201810001-01173.
  • 382 - High Dimensional Immune Phenotyping Using Mass Cytometry Reveals Unique IL1B Signatures in Peripheral Blood and GI Tissue of Ulcerative Colitis, Crohn's Disease, and IL10R Deficient PatientsMitsialis V, Shouval D, Wall S, Snapper S, Konnikova L. 382 - High Dimensional Immune Phenotyping Using Mass Cytometry Reveals Unique IL1B Signatures in Peripheral Blood and GI Tissue of Ulcerative Colitis, Crohn's Disease, and IL10R Deficient Patients Gastroenterology 2018, 154: s-90-s-91. DOI: 10.1016/s0016-5085(18)30750-9.
  • Tu1865 - High Dimensional Immune Phenotyping and Transcriptional Analysis Reveal Robust Recovery of Viable Human Immune and Epithelial Cells from Frozen Gastrointestinal TissueKonnikova L, Boschetti G, Rahman A, Lord J, Richmond C, Tomov V, Gordon W, Canavan J, Wall S, Field M, Zhou F, Bewtra M, Goldsmith J, Breault D, merad M, Snapper S. Tu1865 - High Dimensional Immune Phenotyping and Transcriptional Analysis Reveal Robust Recovery of Viable Human Immune and Epithelial Cells from Frozen Gastrointestinal Tissue Gastroenterology 2018, 154: s-1041-s-1042. DOI: 10.1016/s0016-5085(18)33491-7.
  • P045 HIGH DIMENSIONAL IMMUNE PHENOTYPING AND TRANSCRIPTIONAL ANALYSES REVEAL ROBUST RECOVERY OF VIABLE HUMAN IMMUNE AND EPITHELIAL CELLS FROM CRYOPRESERVED INTESTINAL TISSUEKonnikova L, Boschetti G, Rahman A, Lord J, Richmond C, Tomov V, Gordon W, Jelinsky S, Canavan J, Wall S, Field M, Zhou F, Goldsmith J, Bewtra M, Breault D, Merad M, Snapper S. P045 HIGH DIMENSIONAL IMMUNE PHENOTYPING AND TRANSCRIPTIONAL ANALYSES REVEAL ROBUST RECOVERY OF VIABLE HUMAN IMMUNE AND EPITHELIAL CELLS FROM CRYOPRESERVED INTESTINAL TISSUE Inflammatory Bowel Diseases 2018, 24: s16-s16. DOI: 10.1093/ibd/izy019.051.
  • DOP010 Activating PIK3CD mutations cause severe intestinal lymphonodular hyperplasia and an IBD-like phenotypeFarachi S, Werner L, Konnikova L, Rea F, Vardi I, Romeo E, Barel O, De Angelis P, Dall’Oglio L, Rechavi G, Snapper S, Somech R, Weiss B, Cancrini C, Shouval D. DOP010 Activating PIK3CD mutations cause severe intestinal lymphonodular hyperplasia and an IBD-like phenotype Journal Of Crohn's And Colitis 2018, 12: s036-s037. DOI: 10.1093/ecco-jcc/jjx180.047.
  • P045 HIGH DIMENSIONAL IMMUNE PHENOTYPING AND TRANSCRIPTIONAL ANALYSES REVEAL ROBUST RECOVERY OF VIABLE HUMAN IMMUNE AND EPITHELIAL CELLS FROM CRYOPRESERVED INTESTINAL TISSUEKonnikova L, Boschetti G, Rahman A, Lord J, Richmond C, Tomov V, Gordon W, Jelinsky S, Canavan J, Wall S, Field M, Zhou F, Goldsmith J, Bewtra M, Breault D, Merad M, Snapper S. P045 HIGH DIMENSIONAL IMMUNE PHENOTYPING AND TRANSCRIPTIONAL ANALYSES REVEAL ROBUST RECOVERY OF VIABLE HUMAN IMMUNE AND EPITHELIAL CELLS FROM CRYOPRESERVED INTESTINAL TISSUE Gastroenterology 2018, 154: s23-s24. DOI: 10.1053/j.gastro.2017.11.083.
  • DOP082 Enhanced TH17 responses in patients with IL10 receptor deficiency and history of infantile-onset IBDShouval D, Konnikova L, Werner L, Nunberg M, Weiss B, Glover S, Snapper S. DOP082 Enhanced TH17 responses in patients with IL10 receptor deficiency and history of infantile-onset IBD Journal Of Crohn's And Colitis 2017, 11: s75-s75. DOI: 10.1093/ecco-jcc/jjx002.119.
  • The Role of Nutrition in Health and Disease in Premature Infants: Current Knowledge Gaps and Defining the Research AgendaParker M, Konnikova L, Martin C. The Role of Nutrition in Health and Disease in Premature Infants: Current Knowledge Gaps and Defining the Research Agenda 2012, 111-133. DOI: 10.1007/978-1-62703-224-7_8.