• T cell development
• T cell repertoire
• Inborn errors of immunity
• Severe combined immunodeficiency
• Combined immunodeficiency
• Immunedysregulation disorders
Ottavia Delmonte, M.D., Ph.D., is a physician scientist at National Institute of Health, USA. She has been involved in translational research in primary immune deficiencies (PIDs) and disorders of immune dysregulation since joining the group of Dr. Luigi Notarangelo in 2016. She assists in the development and implementation of clinical research protocols studying immunologic diseases in children and adults with PID and she conducts laboratory research aimed to characterize novel forms of monogenic PIDs and dynamics of immune reconstitution after Hematopoietic Cell Transplantation and/or gene therapy. She is particularly interested in T cell repertoire abnormalities associated with inborn errors of immunity and treatment strategies for PIDs like gene editing and gene correction. In the past 2 years she has described a novel inherited combined immunodeficiency with immune-dysregulation due to SASH3 deficiency and studied T cell repertoire perturbation in multiple newly characterized genetic disorders of the immune system including CD28 and PD1 deficiency. During the COVID-19 pandemic her research focused on virus-host interaction in individuals with life-threatening COVID-19 and multisystem inflammatory disease of children (MIS-C) and on the characterization of immunization responses to SARS-CoV-2 vaccine in patients with PIDs.
She received her M.D., Ph.D. degree from the University of Turin, Italy. She completed a pediatric residency followed by a fellowship in Allergy and Immunology at Boston Children’s Hospital, Harvard University, USA. She speaks Italian and English.
Ottavia Delmonte, M.D., Ph.D., is a physician scientist at National Institute of Health, USA. She has been involved in translational research in primary immune deficiencies (PIDs) and disorders of immune dysregulation since joining the group of Dr. Luigi Notarangelo in 2016. She assists in the development and implementation of clinical research protocols studying immunologic diseases in children and adults with PID and she conducts laboratory research aimed to characterize novel forms of monogenic PIDs and dynamics of immune reconstitution after Hematopoietic Cell Transplantation and/or gene therapy. She is particularly interested in T cell repertoire abnormalities associated with inborn errors of immunity and treatment strategies for PIDs like gene editing and gene correction. In the past 2 years she has described a novel inherited combined immunodeficiency with immune-dysregulation due to SASH3 deficiency and studied T cell repertoire perturbation in multiple newly characterized genetic disorders of the immune system including CD28 and PD1 deficiency. During the COVID-19 pandemic her research focused on virus-host interaction in individuals with life-threatening COVID-19 and multisystem inflammatory disease of children (MIS-C) and on the characterization of immunization responses to SARS-CoV-2 vaccine in patients with PIDs.
Sacco K, Castagnoli R, Vakkilainen S, Liu C, Delmonte OM, Oguz C, Kaplan IM, Alehashemi S, Burbelo PD, Bhuyan F, de Jesus AA, Dobbs K, Rosen LB, Cheng A, Shaw E, Vakkilainen MS, Pala F, Lack J, Zhang Y, Fink DL, Oikonomou V, Snow AL, Dalgard CL, Chen J, Sellers BA, Montealegre Sanchez GA, Barron K, Rey-Jurado E, Vial C, Poli MC, Licari A, Montagna D, Marseglia GL, Licciardi F, Ramenghi U, Discepolo V, Lo Vecchio A, Guarino A, Eisenstein EM, Imberti L, Sottini A, Biondi A, Mató S, Gerstbacher D, Truong M, Stack MA, Magliocco M, Bosticardo M, Kawai T, Danielson JJ, Hulett T, Askenazi M, Hu S; NIAID Immune Response to COVID Group; Chile MIS-C Group; Pavia Pediatric COVID-19 Group, Cohen JI, Su HC, Kuhns DB, Lionakis MS, Snyder TM, Holland SM, Goldbach-Mansky R, Tsang JS, Notarangelo LD. Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19. Nat Med. 2022 May;28(5):1050-1062.
Delmonte OM, Castagnoli R, Yu J, Dvorak CC, Cowan MJ, Dávila Saldaña BJ, De Ravin SS, Mamcarz E, Chang CK, Daley SR, Griffith LM, Notarangelo LD, Puck JM. Poor T-cell receptor β repertoire diversity early posttransplant for severe combined immunodeficiency predicts failure of immune reconstitution. J Allergy Clin Immunol. 2022 Mar;149(3):1113-1119.
Delmonte OM, Bergerson JRE, Burbelo PD, Durkee-Shock JR, Dobbs K, Bosticardo M, Keller MD, McDermott DH, Rao VK, Dimitrova D, Quiros-Roldan E, Imberti L, Ferrè EMN, Schmitt M, Lafeer C, Pfister J, Shaw D, Draper D, Truong M, Ulrick J, DiMaggio T, Urban A, Holland SM, Lionakis MS, Cohen JI, Ricotta EE, Notarangelo LD, Freeman AF. Antibody responses to the SARS-CoV-2 vaccine in individuals with various inborn errors of immunity. J Allergy Clin Immunol. 2021 Nov;148(5):1192-1197.
Delmonte OM, Bergerson JRE, Kawai T, Kuehn HS, McDermott DH, Cortese I, Zimmermann MT, Dobbs AK, Bosticardo M, Fink D, Majumdar S, Palterer B, Pala F, Dsouza NR, Pouzolles M, Taylor N, Calvo KR, Daley SR, Velez D, Agharahimi A, Myint-Hpu K, Dropulic LK, Lyons JJ, Holland SM, Freeman AF, Ghosh R, Similuk MB, Niemela JE, Stoddard J, Kuhns DB, Urrutia R, Rosenzweig SD, Walkiewicz MA, Murphy PM, Notarangelo LD. SASH3 variants cause a novel form of X-linked combined immunodeficiency with immune dysregulation. Blood. 2021 Sep 23;138(12):1019-1033.
Béziat V, Rapaport F, Hu J, Titeux M, Bonnet des Claustres M, Bourgey M, Griffin H, Bandet É, Ma CS, Sherkat R, Rokni-Zadeh H, Louis DM, Changi-Ashtiani M, Delmonte OM, Fukushima T, Habib T, Guennoun A, Khan T, Bender N, Rahman M, About F, Yang R, Rao G, Rouzaud C, Li J, Shearer D, Balogh K, Al Ali F, Ata M, Dabiri S, Momenilandi M, Nammour J, Alyanakian MA, Leruez-Ville M, Guenat D, Materna M, Marcot L, Vladikine N, Soret C, Vahidnezhad H, Youssefian L, Saeidian AH, Uitto J, Catherinot É, Navabi SS, Zarhrate M, Woodley DT, Jeljeli M, Abraham T, Belkaya S, Lorenzo L, Rosain J, Bayat M, Lanternier F, Lortholary O, Zakavi F, Gros P, Orth G, Abel L, Prétet JL, Fraitag S, Jouanguy E, Davis MM, Tangye SG, Notarangelo LD, Marr N, Waterboer T, Langlais D, Doorbar J, Hovnanian A, Christensen N, Bossuyt X, Shahrooei M, Casanova JL. Humans with inherited T cell CD28 deficiency are susceptible to skin papillomaviruses but are otherwise healthy. Cell. 2021 Jul 8;184(14):3812-3828.e30.
Abers MS, Delmonte OM, Ricotta EE, Fintzi J, Fink DL, de Jesus AAA, Zarember KA, Alehashemi S, Oikonomou V, Desai JV, Canna SW, Shakoory B, Dobbs K, Imberti L, Sottini A, Quiros-Roldan E, Castelli F, Rossi C, Brugnoni D, Biondi A, Bettini LR, D'Angio' M, Bonfanti P, Castagnoli R, Montagna D, Licari A, Marseglia GL, Gliniewicz EF, Shaw E, Kahle DE, Rastegar AT, Stack M, Myint-Hpu K, Levinson SL, DiNubile MJ, Chertow DW, Burbelo PD, Cohen JI, Calvo KR, Tsang JS; NIAID COVID-19 Consortium, Su HC, Gallin JI, Kuhns DB, Goldbach-Mansky R, Lionakis MS, Notarangelo LD. An immune-based biomarker signature is associated with mortality in COVID-19 patients. JCI Insight. 2021 Jan 11;6(1):e144455.
• T cell development
• T cell repertoire
• Inborn errors of immunity
• Severe combined immunodeficiency
• Combined immunodeficiency
• Immunedysregulation disorders
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HIV remains a major health issue globally and within the United States. Recent audience research found that many Americans are not aware that HIV is still a health issue in the U.S., are unsure if they might be vulnerable to exposure, and do not know if there is a cure.
Research Training News offers readers an insight into the intramural research training experience and the possibilities this experience can open. Learn about NIAID trainees’ research, their goals, achievements, inspirational moments, and more.
44 Results
Our research program focuses on delineation of the mechanism by which HIV persists in infected individuals receiving clinically effective antiretroviral therapy. We utilize a variety of highly sensitive cellular and molecular assays to examine the dynamics of HIV burden in subsets of CD4+ T cells and immune cells that mediate virologic control in infected individuals. We also conduct phase I clinical trials to develop safe and effective therapeutic strategies for control of HIV infection in HIV-infected individuals in the absence of daily antiretroviral drugs.
Dr. Blazkova received her Ph.D. in Immunology at the Mediterranean University of Aix-Marseille II, France in 2006. Afterwards she conducted postdoctoral research at the Institute of Molecular Genetics, Academy of Sciences of the Czech Republic in Prague. In 2010, Dr. Blazkova joined the Laboratory of Immunoregulation at NIAID as a Visiting Fellow. In 2015, she worked at the Systems Biology Department, Division of Translational Medicine, Sidra Medical and Research Center, Doha, Qatar, for one year as a Senior Postdoctoral Fellow. In 2016, Dr. Blazkova returned to the NIAID and was appointed as a Staff Scientist in the HIV Immunovirology section, LIR.
Blazkova J, Gao F, Marichannegowda MH, Justement JS, Shi V, Whitehead EJ, Schneck RF, Huiting ED, Gittens K, Cottrell M, Benko E, Kovacs C, Lack J, Sneller MC, Moir S, Fauci AS, Chun TW. Distinct mechanisms of long-term virologic control in two HIV-infected individuals after treatment interruption of anti-retroviral therapy. Nat Med. 2021 Nov;27(11):1893-1898.
Blazkova J, Huiting ED, Boddapati AK, Shi V, Whitehead EJ, Justement JS, Nordstrom JL, Moir S, Lack J, Chun TW. Correlation Between TIGIT Expression on CD8+ T Cells and Higher Cytotoxic Capacity. J Infect Dis. 2021 Nov 16;224(9):1599-1604.
Blazkova J, Refsland EW, Clarridge KE, Shi V, Justement JS, Huiting ED, Gittens KR, Chen X, Schmidt SD, Liu C, Doria-Rose N, Mascola JR, Heredia A, Moir S, Chun TW. Glycan-dependent HIV-specific neutralizing antibodies bind to cells of uninfected individuals. J Clin Invest. 2019 Nov 1;129(11):4832-4837.
Wang CY, Wong WW, Tsai HC, Chen YH, Kuo BS, Lynn S, Blazkova J, Clarridge KE, Su HW, Lin CY, Tseng FC, Lai A, Yang FH, Lin CH, Tseng W, Lin HY, Finstad CL, Wong-Staal F, Hanson CV, Chun TW, Liao MJ. Effect of Anti-CD4 Antibody UB-421 on HIV-1 Rebound after Treatment Interruption. N Engl J Med. 2019 Apr 18;380(16):1535-1545.
Our research program focuses on delineation of the mechanism by which HIV persists in infected individuals receiving clinically effective antiretroviral therapy. We utilize a variety of highly sensitive cellular and molecular assays to examine the dynamics of HIV burden in subsets of CD4+ T cells and immune cells that mediate virologic control in infected individuals. We also conduct phase I clinical trials to develop safe and effective therapeutic strategies for control of HIV infection in HIV-infected individuals in the absence of daily antiretroviral drugs.
Blazkova J, Gao F, Marichannegowda MH, Justement JS, Shi V, Whitehead EJ, Schneck RF, Huiting ED, Gittens K, Cottrell M, Benko E, Kovacs C, Lack J, Sneller MC, Moir S, Fauci AS, Chun TW. Distinct mechanisms of long-term virologic control in two HIV-infected individuals after treatment interruption of anti-retroviral therapy. Nat Med. 2021 Nov;27(11):1893-1898.
Blazkova J, Huiting ED, Boddapati AK, Shi V, Whitehead EJ, Justement JS, Nordstrom JL, Moir S, Lack J, Chun TW. Correlation Between TIGIT Expression on CD8+ T Cells and Higher Cytotoxic Capacity. J Infect Dis. 2021 Nov 16;224(9):1599-1604.
Blazkova J, Refsland EW, Clarridge KE, Shi V, Justement JS, Huiting ED, Gittens KR, Chen X, Schmidt SD, Liu C, Doria-Rose N, Mascola JR, Heredia A, Moir S, Chun TW. Glycan-dependent HIV-specific neutralizing antibodies bind to cells of uninfected individuals. J Clin Invest. 2019 Nov 1;129(11):4832-4837.
Wang CY, Wong WW, Tsai HC, Chen YH, Kuo BS, Lynn S, Blazkova J, Clarridge KE, Su HW, Lin CY, Tseng FC, Lai A, Yang FH, Lin CH, Tseng W, Lin HY, Finstad CL, Wong-Staal F, Hanson CV, Chun TW, Liao MJ. Effect of Anti-CD4 Antibody UB-421 on HIV-1 Rebound after Treatment Interruption. N Engl J Med. 2019 Apr 18;380(16):1535-1545.
Bacterial pathogens may undergo dramatic evolution in the context of chronic infection, facilitating host adaptation and the development of antibiotic resistance. Recent studies have illustrated that many general evolutionary processes can be discerned in this context, including genetic diversification of lineages with purifying selection, clonal succession events, and balanced fitness trade-offs. Dr. Ghosh’s research within the Bacterial Pathogenesis and Antimicrobial Resistance Unit (BPARU) focuses on the mechanisms of bacterial pathoadaptation that occurs in the context of persistent infection in the immunocompromised host. These questions are investigated with a combination of genomic sequencing, transcriptome analysis, DNA methylome characterization, and metabolomic profiling. This work aims to understand transcriptional and metabolic reprograming that underlies host adaptation, with implications for clinical treatment of persistent host-adapted infections.
Dr. Ghosh received her Ph.D. in 2015 from the Indian Institute of Science, Bangalore, India, where she used Systems Biology approaches to study host-pathogen interactions in the context of iron acquisition by M. tuberculosis. She joined Johns Hopkins University, Baltimore in 2015 as a post-doctoral research fellow with Dr. Tamara O’Connor in the department of Biological Chemistry. There, she studied convergent evolution in Legionella and how the combined selective pressures of residing in multiple protozoan hosts have equipped Legionella to infect mammalian hosts, including humans. Dr. Ghosh joined the BPARU as a Staff Scientist in December 2021, where she is using her combined training in computational and experimental methods to study bacterial pathogenesis.
Park JM, Ghosh S, O'Connor TJ. Combinatorial selection in amoebal hosts drives the evolution of the human pathogen Legionella pneumophila. Nat Microbiol. 2020 Apr;5(4):599-609.
Ghosh S, O'Connor TJ. Beyond Paralogs: The Multiple Layers of Redundancy in Bacterial Pathogenesis. Front Cell Infect Microbiol. 2017 Nov 15;7:467.
O'Connor TJ, Zheng H, VanRheenen SM, Ghosh S, Cianciotto NP, Isberg RR. Iron Limitation Triggers Early Egress by the Intracellular Bacterial Pathogen Legionella pneumophila. Infect Immun. 2016 Jul 21;84(8):2185-2197.
Ghosh S, Chandra N, Vishveshwara S. Mechanism of Iron-Dependent Repressor (IdeR) Activation and DNA Binding: A Molecular Dynamics and Protein Structure Network Study. PLoS Comput Biol. 2015 Dec 23;11(12):e1004500.
Ghosh S, Baloni P, Mukherjee S, Anand P, Chandra N. A multi-level multi-scale approach to study essential genes in Mycobacterium tuberculosis. BMC Syst Biol. 2013 Dec 5;7:132.
Ghosh S, Prasad KV, Vishveshwara S, Chandra N. Rule-based modelling of iron homeostasis in tuberculosis. Mol Biosyst. 2011 Oct;7(10):2750-68.
Bacterial pathogens may undergo dramatic evolution in the context of chronic infection, facilitating host adaptation and the development of antibiotic resistance. Recent studies have illustrated that many general evolutionary processes can be discerned in this context, including genetic diversification of lineages with purifying selection, clonal succession events, and balanced fitness trade-offs. Dr. Ghosh’s research within the Bacterial Pathogenesis and Antimicrobial Resistance Section (BPARS) focuses on the mechanisms of bacterial pathoadaptation that occurs in the context of persistent infection in the immunocompromised host. These questions are investigated with a combination of genomic sequencing, transcriptome analysis, DNA methylome characterization, and metabolomic profiling. This work aims to understand transcriptional and metabolic reprograming that underlies host adaptation, with implications for clinical treatment of persistent host-adapted infections.
Park JM, Ghosh S, O'Connor TJ. Combinatorial selection in amoebal hosts drives the evolution of the human pathogen Legionella pneumophila. Nat Microbiol. 2020 Apr;5(4):599-609.
Ghosh S, O'Connor TJ. Beyond Paralogs: The Multiple Layers of Redundancy in Bacterial Pathogenesis. Front Cell Infect Microbiol. 2017 Nov 15;7:467.
O'Connor TJ, Zheng H, VanRheenen SM, Ghosh S, Cianciotto NP, Isberg RR. Iron Limitation Triggers Early Egress by the Intracellular Bacterial Pathogen Legionella pneumophila. Infect Immun. 2016 Jul 21;84(8):2185-2197.
Ghosh S, Chandra N, Vishveshwara S. Mechanism of Iron-Dependent Repressor (IdeR) Activation and DNA Binding: A Molecular Dynamics and Protein Structure Network Study. PLoS Comput Biol. 2015 Dec 23;11(12):e1004500.
Ghosh S, Baloni P, Mukherjee S, Anand P, Chandra N. A multi-level multi-scale approach to study essential genes in Mycobacterium tuberculosis. BMC Syst Biol. 2013 Dec 5;7:132.
Ghosh S, Prasad KV, Vishveshwara S, Chandra N. Rule-based modelling of iron homeostasis in tuberculosis. Mol Biosyst. 2011 Oct;7(10):2750-68.
