Devil in the Coronavirus Fusion Details

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Devil in the Coronavirus Fusion Details
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Albert Einstein College of Medicine Receives $11.3M NIH Grant to Expand the Einstein-Rockefeller-CUNY Center for AIDS Research

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Albert Einstein College of Medicine
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Albert Einstein College of Medicine Receives $11.3M NIH Grant
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Recurrent UTIs Linked to Gut Microbiome, Chronic Inflammation

Ottavia Maria Delmonte, M.D., Ph.D.

Assistant Research Physician

Major Areas of Research

•    T cell development
•    T cell repertoire
•    Inborn errors of immunity
•    Severe combined immunodeficiency
•    Combined immunodeficiency
•    Immunedysregulation disorders 
 

Program Description

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. 

Biography

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. 

Publications

  • 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. 

Visit PubMed for a complete publication listing.

Section or Unit Name
Immunodeficiency and Genetics Section (IDGS)
First Name
Ottavia
Last Name
Delmonte
Middle Name
M.
Suffix
M.D., Ph.D.
Exclude from directory
Off
Section/Unit: Location
This Researcher/Clinician’s Person Page
Program Description

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.

Selected Publications

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.


Visit PubMed for a complete publication listing.

Major Areas of Research

•    T cell development
•    T cell repertoire
•    Inborn errors of immunity
•    Severe combined immunodeficiency
•    Combined immunodeficiency
•    Immunedysregulation disorders 

Research Training at NIAID

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To promote and develop the next generation of biomedical researchers, NIAID is committed to offering a broad spectrum of training opportunities to individuals from varying educational backgrounds, ranging from high school to postdoctoral level. NIAID strives to provide resources and support for fellows at all levels to further the mission of training the next generation of scientific leaders.

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Trainees will conduct research focused on understanding, treating, and preventing infectious, immunologic, and allergic diseases in NIAID laboratories located in Maryland and Montana (Rocky Mountain Laboratories in Hamilton), providing a unique scientific research training environment in basic, translational, and clinical research. Learn more about the labs at NIAID:

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    and coaching
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Help End HIV - Red Ribbon Registry

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 & Events

Jana Blazkova, Ph.D.

Staff Scientist, HIV Immunovirology Section

Major Areas of Research

  • Mechanisms of viral persistence in HIV-infected individuals receiving antiretroviral therapy
  • Dynamics of immunologic and virologic parameters in HIV infection
  • Therapeutic strategies aiming at achieving sustained virologic control of HIV infection

Program Description

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. 

Biography

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.

Selected Publications

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.

Section or Unit Name
HIV Immunovirology Section
First Name
Jana
Last Name
Blazkova
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Section/Unit: Location
This Researcher/Clinician’s Person Page
Parent Lab/Program
Program Description

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. 

Selected Publications

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.

Major Areas of Research
  • Mechanisms of viral persistence in HIV-infected individuals receiving antiretroviral therapy
  • Dynamics of immunologic and virologic parameters in HIV infection
  • Therapeutic strategies aiming at achieving sustained virologic control of HIV infection

Soma Ghosh, Ph.D.

Staff Scientist

Major Areas of Research

  • Within-host evolution of Gram-negative bacterial pathogens in the context of chronic infection and immunodeficiency
  • Transcriptional and metabolic reprogramming that occurs during host adaptation
  • DNA methylation and epigenetic regulation of bacterial virulence and antibiotic resistance

Program Description

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.

Biography

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.

Selected Publications

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.

Visit PubMed for a full list of publications.

Section or Unit Name
Bacterial Pathogenesis and Antimicrobial Resistance Section
First Name
Soma
Last Name
Ghosh
Suffix
Ph.D.
Exclude from directory
Off
Section/Unit: Location
This Researcher/Clinician’s Person Page
Program Description

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.

Selected Publications

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.

Visit PubMed for a full list of publications.

Major Areas of Research
  • Within-host evolution of Gram-negative bacterial pathogens in the context of chronic infection and immunodeficiency
  • Transcriptional and metabolic reprogramming that occurs during host adaptation
  • DNA methylation and epigenetic regulation of bacterial virulence and antibiotic resistance

Ray Y. Chen

Staff Clinician, Associate Research Physician

Major Areas of Research

Tuberculosis

Program Description

Clinical trials focused on diagnostics, novel treatment strategies, and treatment shortening methodologies for tuberculosis.

Biography

Dr. Chen graduated from the Medical College of Virginia/Virginia Commonwealth University in Richmond, Virginia, then trained in Internal Medicine at the Thomas Jefferson University Hospital in Philadelphia, Pennsylvania and in Infectious Diseases at the University of Alabama at Birmingham (UAB). While at UAB, he also earned a Master of Science in Public Health with a concentration in epidemiology.

Dr. Chen came to NIAID in 2003 to the Division of AIDS (DAIDS) and was based in Beijing, China for DAIDS from 2004-2012, working with Chinese investigators. In 2012, he returned to Bethesda, MD and joined the Tuberculosis Research Section in the Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research.

Selected Publications

Chen RY, Yu X, Smith B, Liu X, Gao J, Diacon AH, Dawson R, Tameris M, Zhu H, Qu Y, Zhang R, Pan S, Jin X, Goldfeder LC, Cai Y, Arora K, Wang J, Vincent J, Malherbe ST, Thienemann F, Wilkinson RJ, Walzl G, Barry CE 3rd. Radiological and functional evidence of the bronchial spread of tuberculosis: an observational analysis. Lancet Microbe. 2021 Oct;2(10):e518-e526.

Xie YL, de Jager VR, Chen RY, Dodd LE, Paripati P, Via LE, Follmann D, Wang J, Lumbard K, Lahouar S, Malherbe ST, Andrews J, Yu X, Goldfeder LC, Cai Y, Arora K, Loxton AG, Vanker N, Duvenhage M, Winter J, Song T, Walzl G, Diacon AH, Barry CE 3rd. Fourteen-day PET/CT imaging to monitor drug combination activity in treated individuals with tuberculosis. Sci Transl Med. 2021 Feb 3;13(579):eabd7618.

Lee A, Xie YL, Barry CE, Chen RY. Current and future treatments for tuberculosis. BMJ. 2020 Mar 2;368:m216.

Xie YL, Chakravorty S, Armstrong DT, Hall SL, Via LE, Song T, Yuan X, Mo X, Zhu H, Xu P, Gao Q, Lee M, Lee J, Smith LE, Chen RY, Joh JS, Cho Y, Liu X, Ruan X, Liang L, Dharan N, Cho SN, Barry CE 3rd, Ellner JJ, Dorman SE, Alland D. Evaluation of a Rapid Molecular Drug-Susceptibility Test for Tuberculosis. N Engl J Med. 2017 Sep 14;377(11):1043-1054.

Malherbe ST, Shenai S, Ronacher K, Loxton AG, Dolganov G, Kriel M, Van T, Chen RY, Warwick J, Via LE, Song T, Lee M, Schoolnik G, Tromp G, Alland D, Barry CE 3rd, Winter J, Walzl G; Catalysis TB–Biomarker Consortium, Lucas L, Spuy GV, Stanley K, Thiart L, Smith B, Du Plessis N, Beltran CG, Maasdorp E, Ellmann A, Choi H, Joh J, Dodd LE, Allwood B, Koegelenberg C, Vorster M, Griffith-Richards S. Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure. Nat Med. 2016 Oct;22(10):1094-1100.

Chen RY, Dodd LE, Lee M, Paripati P, Hammoud DA, Mountz JM, Jeon D, Zia N, Zahiri H, Coleman MT, Carroll MW, Lee JD, Jeong YJ, Herscovitch P, Lahouar S, Tartakovsky M, Rosenthal A, Somaiyya S, Lee S, Goldfeder LC, Cai Y, Via LE, Park SK, Cho SN, Barry CE 3rd. PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis. Sci Transl Med. 2014 Dec 3;6(265):265ra166.

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Section or Unit Name
Tuberculosis Research Section
First Name
Ray
Last Name
Chen
Middle Name
Y
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Program Description

Clinical trials focused on diagnostics, novel treatment strategies, and treatment shortening methodologies for tuberculosis.

Selected Publications

Chen RY, Yu X, Smith B, Liu X, Gao J, Diacon AH, Dawson R, Tameris M, Zhu H, Qu Y, Zhang R, Pan S, Jin X, Goldfeder LC, Cai Y, Arora K, Wang J, Vincent J, Malherbe ST, Thienemann F, Wilkinson RJ, Walzl G, Barry CE 3rd. Radiological and functional evidence of the bronchial spread of tuberculosis: an observational analysis. Lancet Microbe. 2021 Oct;2(10):e518-e526.

Xie YL, de Jager VR, Chen RY, Dodd LE, Paripati P, Via LE, Follmann D, Wang J, Lumbard K, Lahouar S, Malherbe ST, Andrews J, Yu X, Goldfeder LC, Cai Y, Arora K, Loxton AG, Vanker N, Duvenhage M, Winter J, Song T, Walzl G, Diacon AH, Barry CE 3rd. Fourteen-day PET/CT imaging to monitor drug combination activity in treated individuals with tuberculosis. Sci Transl Med. 2021 Feb 3;13(579):eabd7618.

Lee A, Xie YL, Barry CE, Chen RY. Current and future treatments for tuberculosis. BMJ. 2020 Mar 2;368:m216.

Xie YL, Chakravorty S, Armstrong DT, Hall SL, Via LE, Song T, Yuan X, Mo X, Zhu H, Xu P, Gao Q, Lee M, Lee J, Smith LE, Chen RY, Joh JS, Cho Y, Liu X, Ruan X, Liang L, Dharan N, Cho SN, Barry CE 3rd, Ellner JJ, Dorman SE, Alland D. Evaluation of a Rapid Molecular Drug-Susceptibility Test for Tuberculosis. N Engl J Med. 2017 Sep 14;377(11):1043-1054.

Malherbe ST, Shenai S, Ronacher K, Loxton AG, Dolganov G, Kriel M, Van T, Chen RY, Warwick J, Via LE, Song T, Lee M, Schoolnik G, Tromp G, Alland D, Barry CE 3rd, Winter J, Walzl G; Catalysis TB–Biomarker Consortium, Lucas L, Spuy GV, Stanley K, Thiart L, Smith B, Du Plessis N, Beltran CG, Maasdorp E, Ellmann A, Choi H, Joh J, Dodd LE, Allwood B, Koegelenberg C, Vorster M, Griffith-Richards S. Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure. Nat Med. 2016 Oct;22(10):1094-1100.

Chen RY, Dodd LE, Lee M, Paripati P, Hammoud DA, Mountz JM, Jeon D, Zia N, Zahiri H, Coleman MT, Carroll MW, Lee JD, Jeong YJ, Herscovitch P, Lahouar S, Tartakovsky M, Rosenthal A, Somaiyya S, Lee S, Goldfeder LC, Cai Y, Via LE, Park SK, Cho SN, Barry CE 3rd. PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis. Sci Transl Med. 2014 Dec 3;6(265):265ra166.

Visit PubMed for a complete publication listing.

Major Areas of Research
  • Tuberculosis