UTHSC Team Receives $2.84 Million To Study Flu Infections

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Research Institution
University of Tennessee Health Science Center
Short Title
UTHSC Team Receives $2.84 Million To Study Flu Infections

Andrea Lisco, M.D., Ph.D.

Assistant Clinical Investigator

Major Areas of Research

  • Immunological, genetic and virological determinants of the susceptibility to severe HPV-related diseases
  • Viral pathogenesis in skin and mucosal surfaces of patients with primary and acquired immunodeficiencies
  • Immune-based therapeutic strategies of severe HPV-related diseases

Program Description

Primary and acquired immunodeficiencies like HIV/AIDS are associated with high prevalence of skin and mucosal diseases caused by Human Papillomaviruses (HPV) as well as an accelerated progression to HPV-related cancers. Dr. Lisco`s primary focus is on delineating the genetic, immunological, and molecular determinants of persistence, regression, or progression of HPV-related diseases to inform innovative preventive and therapeutic strategies.

The translational workflow of the laboratory is based on the integration of clinical protocols focused on the identification of clinical and epidemiological predictors of severe HPV-related diseases with studies on host genetics and tissue-specific immunopathogenesis at the skin and mucosal barriers eventually informing personalized interventional clinical protocols.

Biography

Dr. Lisco earned his medical degree at University of Bari, Italy and pursued his research interests in viral immunology and pathogenesis of oncogenic viruses during his Ph.D. at the University of Padua, Italy and post-doctoral fellowship at the National Institutes of Health. He then underwent his internal medicine residency training at Case Western University Hospitals Cleveland Medical Center and returned to the NIH to complete his fellowship training in infectious disease at NIAID. Since 2018, Dr. Lisco is an Assistant Clinical Investigator at NIAID.

Publications

Lisco A, Hsu AP, Dimitrova D, Proctor DM, Mace EM, Ye P, Anderson MV, Hicks SN, Grivas C, Hammoud DA, Manion M, Starrett GJ, Farrel A, Dobbs K, Brownell I, Buck C, Notarangelo LD, Orange JS, Leonard WJ, Orestes MI, Peters AT, Kanakry JA, Segre JA, Kong HH, Sereti I. Treatment of Relapsing HPV Diseases by Restored Function of Natural Killer Cells. N Engl J Med. 2021 Sep 2;385(10):921-929.

Lisco A, Ye P, Wong CS, Pei L, Hsu AP, Mace EM, Orange JS, Lage SL, Ward AJ, Migueles SA, Connors M, Anderson MV, Buckner CM, Moir S, Rupert A, Dulau-Florea A, Ogbogu P, Timberlake D, Notarangelo LD, Pittaluga S, Abraham RS, Sereti I. Lost in Translation: Lack of CD4 Expression due to a Novel Genetic Defect. J Infect Dis. 2021 Feb 24;223(4):645-654.

Lisco A, Wong CS, Lage SL, Levy I, Brophy J, Lennox J, Manion M, Anderson MV, Mejia Y, Grivas C, Mystakelis H, Burbelo PD, Perez-Diez A, Rupert A, Martens CA, Anzick SL, Morse C, Chan S, Deleage C, Sereti I. Identification of rare HIV-1-infected patients with extreme CD4+ T cell decline despite ART-mediated viral suppression. JCI Insight. 2019 Apr 18;4(8):e127113.

Pastrana DV, Peretti A, Welch NL, Borgogna C, Olivero C, Badolato R, Notarangelo LD, Gariglio M, FitzGerald PC, McIntosh CE, Reeves J, Starrett GJ, Bliskovsky V, Velez D, Brownell I, Yarchoan R, Wyvill KM, Uldrick TS, Maldarelli F, Lisco A, Sereti I, Gonzalez CM, Androphy EJ, McBride AA, Van Doorslaer K, Garcia F, Dvoretzky I, Liu JS, Han J, Murphy PM, McDermott DH, Buck CB. Metagenomic Discovery of 83 New Human Papillomavirus Types in Patients with Immunodeficiency. mSphere. 2018 Dec 12;3(6):e00645-18.

Lisco A, Munawwar A, Introini A, Vanpouille C, Saba E, Feng X, Grivel JC, Singh S, Margolis L. Semen of HIV-1-infected individuals: local shedding of herpesviruses and reprogrammed cytokine network. J Infect Dis. 2012 Jan 1;205(1):97-105.

Saba E, Grivel JC, Vanpouille C, Brichacek B, Fitzgerald W, Margolis L, Lisco A. HIV-1 sexual transmission: early events of HIV-1 infection of human cervico-vaginal tissue in an optimized ex vivo model. Mucosal Immunol. 2010 May;3(3):280-90.

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Research Group

Peiying Ye, Ph.D., Biologist

Section or Unit Name
Mucosal and Cutaneous Viral Immunopathogenesis Unit (MCVIU)
First Name
Andrea
Last Name
Lisco
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Parent Lab/Program
Program Description

Primary and acquired immunodeficiencies like HIV/AIDS are associated with a high prevalence of skin and mucosal diseases caused by the Human Papillomaviruses (HPV), as well as an accelerated progression to HPV-related cancers. Dr. Lisco`s primary focus is on delineating the genetic, immunological, and molecular determinants of the persistence, regression, or progression of HPV-related diseases to inform innovative preventive and therapeutic strategies.

The translational workflow of the laboratory is based on the integration of clinical protocols focused on the identification of clinical and epidemiological predictors of severe HPV-related diseases with studies on host genetics and tissue-specific immunopathogenesis at the skin and mucosal barriers, eventually informing personalized interventional clinical protocols.

Selected Publications

Lisco A, Ortega-Villa AM, Mystakelis H, Anderson MV, Mateja A, Laidlaw E, Manion M, Roby G, Higgins J, Kuriakose S, Walkiewicz MA, Similuk M, Leiding JW, Freeman AF, Sheikh V, Sereti I. Reappraisal of Idiopathic CD4 Lymphocytopenia at 30 Years. N Engl J Med. 2023 May 4;388(18):1680-1691.

Lisco A, Hsu AP, Dimitrova D, Proctor DM, Mace EM, Ye P, Anderson MV, Hicks SN, Grivas C, Hammoud DA, Manion M, Starrett GJ, Farrel A, Dobbs K, Brownell I, Buck C, Notarangelo LD, Orange JS, Leonard WJ, Orestes MI, Peters AT, Kanakry JA, Segre JA, Kong HH, Sereti I. Treatment of Relapsing HPV Diseases by Restored Function of Natural Killer Cells. N Engl J Med. 2021 Sep 2;385(10):921-929.

Lisco A, Ye P, Wong CS, Pei L, Hsu AP, Mace EM, Orange JS, Lage SL, Ward AJ, Migueles SA, Connors M, Anderson MV, Buckner CM, Moir S, Rupert A, Dulau-Florea A, Ogbogu P, Timberlake D, Notarangelo LD, Pittaluga S, Abraham RS, Sereti I. Lost in Translation: Lack of CD4 Expression due to a Novel Genetic Defect. J Infect Dis. 2021 Feb 24;223(4):645-654.

Lisco A, Wong CS, Lage SL, Levy I, Brophy J, Lennox J, Manion M, Anderson MV, Mejia Y, Grivas C, Mystakelis H, Burbelo PD, Perez-Diez A, Rupert A, Martens CA, Anzick SL, Morse C, Chan S, Deleage C, Sereti I. Identification of rare HIV-1-infected patients with extreme CD4+ T cell decline despite ART-mediated viral suppression. JCI Insight. 2019 Apr 18;4(8):e127113.

Pastrana DV, Peretti A, Welch NL, Borgogna C, Olivero C, Badolato R, Notarangelo LD, Gariglio M, FitzGerald PC, McIntosh CE, Reeves J, Starrett GJ, Bliskovsky V, Velez D, Brownell I, Yarchoan R, Wyvill KM, Uldrick TS, Maldarelli F, Lisco A, Sereti I, Gonzalez CM, Androphy EJ, McBride AA, Van Doorslaer K, Garcia F, Dvoretzky I, Liu JS, Han J, Murphy PM, McDermott DH, Buck CB. Metagenomic Discovery of 83 New Human Papillomavirus Types in Patients with Immunodeficiency. mSphere. 2018 Dec 12;3(6):e00645-18.

Lisco A, Munawwar A, Introini A, Vanpouille C, Saba E, Feng X, Grivel JC, Singh S, Margolis L. Semen of HIV-1-infected individuals: local shedding of herpesviruses and reprogrammed cytokine network. J Infect Dis. 2012 Jan 1;205(1):97-105.

Visit PubMed for a complete publication listing.

Additional Information
Major Areas of Research
  • Immunological, genetic and virological determinants of the susceptibility to severe HPV-related diseases
  • Viral pathogenesis in skin and mucosal surfaces of patients with primary and acquired immunodeficiencies
  • Immune-based therapeutic strategies of severe HPV-related diseases
Research Group Page

Philip M. Murphy, M.D.

Major Areas of Research

  • Host defense and inflammation
  • G protein-coupled chemoattractant receptors
  • Genetic risk factors in infectious and immune-mediated diseases
  • Primary immunodeficiency disease

Program Description

This laboratory studies G protein-coupled receptors of the immune system. These include a large family of chemokine receptors and a smaller group of classical chemoattractant receptors, which together differentially regulate specific leukocyte trafficking in support of innate and adaptive immune responses.

The goal of the lab is to delineate the precise mechanisms by which the receptors relay chemotactic signals to cells and to identify their exact physiologic roles both in immunoregulation and in immunologically mediated disease. The approaches used are to isolate specific chemoattractant receptors by molecular cloning, to examine their signal transduction properties both in model cell systems and in primary cells, and to study their biology in mouse models and, where possible, in patients through direct clinical research.

Further, the lab has a program in human immunogenomics in which genetic polymorphisms discovered in candidate chemoattractant or chemoattractant receptor genes are checked for effects on biochemical function and for associations with specific diseases. Major discoveries include the following:

  • Identification of the first CXC, CC, and CX3C chemokine receptor subtypes, as well as numerous other members of the chemokine receptor family, and characterization of their ligand and leukocyte specificities
  • Characterization of the f-Met-Leu-Phe receptor (FPR) family
  • Identification of CCR5 and demonstration that CCR5 is a major HIV receptor in vivo by analysis of the defective genetic variant CCR5Δ32
  • Characterization of the first viral mimics of chemokine receptors
  • Discovery of novel genetic risk factors in atherosclerosis, HIV/AIDS, West Nile virus infection, and kidney transplant rejection
  • Characterization of G6PC3 deficiency, a novel immunodeficiency syndrome characterized by severe congenital neutropenia and recurrent bacterial infections
  • Development of novel therapeutic approach for patients with the primary immunodeficiency disorder WHIM syndrome

There are projects ongoing in the lab extending each of these observations.

Biography

Dr. Murphy obtained an A.B. from Princeton University in 1975 and an M.D. from Cornell University Medical College in 1981. He trained in internal medicine at New York University from 1981 to 1985, serving as chief resident from 1984 to 1985, and in infectious diseases at NIAID from 1985 to 1988.

He began his research career as a medical staff fellow in the Bacterial Diseases Section of the NIAID Laboratory of Clinical Investigation in 1986 and was promoted to senior investigator with tenure in the Laboratory of Host Defenses (LHD) in 1992. In 1998, he was promoted to the Senior Biomedical Research Service and named chief of the LHD Molecular Signaling Section.

In 2003, Dr. Murphy’s research group was reorganized as part of the new Laboratory of Molecular Immunology, where he served first as acting chief from 2003 to 2006 and then as chief from 2006 to the present. Dr. Murphy’s research interests include immunoregulation by chemokines and related chemoattractants.

Section or Unit Name
Molecular Signaling Section
First Name
Philip
Last Name
Murphy
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Program Description

The Molecular Signaling Section studies basic principles and clinical correlates of leukocyte chemoattractants and their G protein-coupled receptors. The chemoattractants under study include a large family of chemokines and a smaller group of classical chemoattractants, which together differentially regulate specific leukocyte trafficking in support of both immune homeostasis and innate and adaptive immune responses.  The scope of research includes basic investigation of chemoattractant signaling and leukocyte trafficking, the role of chemoattractants in immunoregulation in both homeostatic and disease conditions, and clinical correlates of chemoattractant action. Pathogens under study include SARS-CoV-2, E. coli, Trypanosoma cruzi and Toxoplasma gondi. The clinical program investigates inborn errors of immunity, including WHIM syndrome, G6PC3 deficiency, and SASH3 deficiency and is developing new drug treatments, as well as gene therapy and allotransplantation cure strategies for affected patients.  Mouse models of infection and immunodeficiency disease are used to dissect mechanisms of pathogenesis and for preclinical trials of novel interventions.

Major discoveries of the Molecular Signaling Section include the following:

  • Discovery of the first CXC, CC, and CX3C chemokine receptor subtypes, as well as other members of the chemokine receptor family, and characterization of their ligand and leukocyte specificities
  • Characterization of the f-Met-Leu-Phe receptor (FPR) family
  • Discovery of CCR5 and delineation of both its chemokine receptor and HIV coreceptor activities; discovery of the HIV/AIDS genetic restriction factor CCR5Δ32
  • Discovery of the first virally-encoded chemokine receptors, ECRF3 of Herpesvirus saimiri and US28 of Human Cytomegalovirus
  • Discovery of genetic risk factors in patients with atherosclerosis, HIV/AIDS, West Nile virus infection, and kidney transplant rejection
  • Discovery of a subtype of G6PC3 deficiency, a rare primary immunodeficiency disease characterized by severe congenital neutropenia due to defects in glucose metabolism that predispose to recurrent bacterial infection
  • Development of the CXCR4 antagonist plerixafor as targeted therapy in the combined primary immunodeficiency disorder WHIM syndrome
  • Discovery of anionic phospholipids as the third class of chemokine binding factors (the other two being G protein-coupled receptors and glycosaminoglycans); discovery of chemokine binding to phosphatidyl serine as a find-me signal in apoptotic cell clearance and chemokine binding to cardiolipin as a key mechanism responsible for direct chemokine antimicrobial activity
  • Discovery of anti CD117-saporin immunotoxin as a safe conditioning method for establishment of high-level hematopoietic chimerism and donor-specific tolerance in a complete immunologically mismatched mouse model of bone marrow allotransplantation
  • Discovery of spontaneous chromothriptic cure of WHIM syndrome in a patient by deletion of the disease allele of CXCR4, but not the wild type CXCR4 allele, in a single hematopoietic stem cell 

There are projects ongoing in the lab extending each of these observations.

Selected Publications

McDermott DH, Velez D, Cho E, Cowen EW, DiGiovanna JJ, Pastrana DV, Buck CB, Calvo KR, Gardner PJ, Rosenzweig SD, Stratton P, Merideth MA, Kim HJ, Brewer C, Katz JD, Kuhns DB, Malech HL, Follmann D, Fay MP, Murphy PM. A phase III randomized crossover trial of plerixafor versus G-CSF for treatment of WHIM syndrome. J Clin Invest. 2023 Oct 2;133(19):e164918.

Pontejo SM, Murphy PM. Chemokines act as phosphatidylserine-bound "find-me" signals in apoptotic cell clearance. PLoS Biol. 2021 May 26;19(5):e3001259.

Li Z, Czechowicz A, Scheck A, Rossi DJ, Murphy PM. Hematopoietic chimerism and donor-specific skin allograft tolerance after non-genotoxic CD117 antibody-drug-conjugate conditioning in MHC-mismatched allotransplantation. Nat Commun. 2019 Feb 6;10(1):616.

McDermott DH, Pastrana DV, Calvo KR, Pittaluga S, Velez D, Cho E, Liu Q, Trout HH 3rd, Neves JF, Gardner PJ, Bianchi DA, Blair EA, Landon EM, Silva SL, Buck CB, Murphy PM. Plerixafor for the Treatment of WHIM Syndrome. N Engl J Med. 2019 Jan 10;380(2):163-170.

McDermott DH, Gao JL, Liu Q, Siwicki M, Martens C, Jacobs P, Velez D, Yim E, Bryke CR, Hsu N, Dai Z, Marquesen MM, Stregevsky E, Kwatemaa N, Theobald N, Long Priel DA, Pittaluga S, Raffeld MA, Calvo KR, Maric I, Desmond R, Holmes KL, Kuhns DB, Balabanian K, Bachelerie F, Porcella SF, Malech HL, Murphy PM. Chromothriptic cure of WHIM syndrome. Cell. 2015 Feb 12;160(4):686-699.

Murphy PM, Tiffany HL. Cloning of complementary DNA encoding a functional human interleukin-8 receptor. Science. 1991. 253: 1280-1283. J Immunol. 2009 Sep 1;183(5):2898-901. 

Visit PubMed for a complete publication list.

Major Areas of Research
  • Host defense and inflammation
  • G protein-coupled chemoattractant receptors
  • Genetic risk factors in infectious and immune-mediated diseases
  • Primary immunodeficiency disease

Notice of Special Interest (NOSI)—Research on the Health of Sexual and Gender Minority (SGM) Populations

Stephen A. Migueles, M.D.

Head, Cellular Immune Response Unit
HIV-Specific Immunity Section, Laboratory of Immunoregulation
  • Cellular immune response to HIV, SARS-CoV-2 and other infections
  • Mechanisms of durable immunologic control of HIV in rare patients
  • Basic immunology of vaccine-induced responses
  • Studies in a cohort of People Living with HIV Infection in Liberia, West Africa

Program Description

The major focus of the Cellular Immune Response Unit/HIV-Specific Immunity Section is identification of the mechanisms of an effective cellular immune response to HIV and other viral infections. Investigations are performed by various techniques on samples from rare patients, termed long-term nonprogressors (LTNPs) or elite controllers, who have exhibited spontaneous control of HIV replication for decades. Detailed characterization of their virus-specific T-cell responses is a critical step toward the development of effective vaccines and immunotherapies and provides fundamental insights into the regulation of human immune responses in viral infection and other disease states.

Biography

Dr. Migueles received his M.D. from the University of Miami School of Medicine in 1993. He then completed an internship, residency and chief residency in Internal Medicine at Georgetown University Medical Center. In 1997, Dr. Migueles came to the National Institute of Allergy and Infectious Diseases as a Clinical Associate in the Laboratory of Immunoregulation and was commissioned as a Medical Officer in the U.S. Public Health Service (USPHS). He became a Staff Clinician in 2005, Senior Research Physician in 2017 and Head of the Cellular Immune Response Unit in 2019. Dr. Migueles was promoted to CAPT (0-6) in the USPHS in 2010. He maintains active certification in Internal Medicine and Infectious Diseases (current diplomate, American Board of Internal Medicine).

Selected Publications

Section or Unit Name
Cellular Immune Response Unit
First Name
Stephen
Last Name
Migueles
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Parent Lab/Program
Program Description

The major focus of the Cellular Immune Response Unit/HIV-Specific Immunity Section is identification of the mechanisms of an effective cellular immune response to HIV and other viral infections. Investigations are performed by various techniques on samples from rare patients, termed long-term nonprogressors (LTNPs) or elite controllers, who have exhibited spontaneous control of HIV replication for decades. Detailed characterization of their virus-specific T-cell responses is a critical step toward the development of effective vaccines and immunotherapies and provides fundamental insights into the regulation of human immune responses in viral infection and other disease states.

Selected Publications

Matsuda K, Migueles SA, Huang J, Bolkhovitinov L, Stuccio S, Griesman T, Pullano AA, Kang BH, Ishida E, Zimmerman M, Kashyap N, Martins KM, Stadlbauer D, Pederson J, Patamawenu A, Wright N, Shofner T, Evans S, Liang CJ, Candia J, Biancotto A, Fantoni G, Poole A, Smith J, Alexander J, Gurwith M, Krammer F, Connors M. A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity. J Clin Invest. 2021 Mar 1;131(5):e140794.

Migueles SA, Rogan DC, Gavil NV, Kelly EP, Toulmin SA, Wang LT, Lack J, Ward AJ, Pryal PF, Ludwig AK, Medina RG, Apple BJ, Toumanios CN, Poole AL, Rehm CA, Jones SE, Liang CJ, Connors M. Antigenic Restimulation of Virus-Specific Memory CD8+ T Cells Requires Days of Lytic Protein Accumulation for Maximal Cytotoxic Capacity. J Virol. 2020 Nov 9;94(23):e01595-20.

Migueles SA, Chairez C, Lin S, Gavil NV, Rosenthal DM, Pooran M, Natarajan V, Rupert A, Dewar R, Rehman T, Sherman BT, Adelsberger J, Leitman SF, Stroncek D, Morse CG, Connors M, Lane HC, Kovacs JA. Adoptive lymphocyte transfer to an HIV-infected progressor from an elite controller. JCI Insight. 2019 Sep 19;4(18):e130664.

Mendoza D, Johnson SA, Peterson BA, Natarajan V, Salgado M, Dewar RL, Burbelo PD, Doria-Rose NA, Graf EH, Greenwald JH, Hodge JN, Thompson WL, Cogliano NA, Chairez CL, Rehm CA, Jones S, Hallahan CW, Kovacs JA, Sereti I, Sued O, Peel SA, O'Connell RJ, O'Doherty U, Chun TW, Connors M, Migueles SA. Comprehensive analysis of unique cases with extraordinary control over HIV replication. Blood. 2012 May 17;119(20):4645-55.

Migueles SA, Rood JE, Berkley AM, Guo T, Mendoza D, Patamawenu A, Hallahan CW, Cogliano NA, Frahm N, Duerr A, McElrath MJ, Connors M. Trivalent adenovirus type 5 HIV recombinant vaccine primes for modest cytotoxic capacity that is greatest in humans with protective HLA class I alleles. PLoS Pathog. 2011 Feb;7(2):e1002002.

Migueles SA, Osborne CM, Royce C, Compton AA, Joshi RP, Weeks KA, Rood JE, Berkley AM, Sacha JB, Cogliano-Shutta NA, Lloyd M, Roby G, Kwan R, McLaughlin M, Stallings S, Rehm C, O'Shea MA, Mican J, Packard BZ, Komoriya A, Palmer S, Wiegand AP, Maldarelli F, Coffin JM, Mellors JW, Hallahan CW, Follman DA, Connors M. Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. Immunity. 2008 Dec 19;29(6):1009-21.

Major Areas of Research
  • Cellular immune response to HIV, SARS-CoV-2 and other infections
  • Mechanisms of durable immunologic control of HIV in rare patients
  • Basic immunology of vaccine-induced responses
  • Studies in a cohort of People Living with HIV Infection in Liberia, West Africa

Jianbing Mu, M.D., Ph.D.

Associate Scientist (Core)

Major Areas of Research

  • Genetic and epigenetic gene regulations in Plasmodium parasites
  • Molecular biology of malaria pathogenesis

Program Description

  • Parasites genetic diversity and associated phenotypes, such as antimalarial drug resistance and parasites virulence factors
  • Epigenetic and epitranscriptomic modifications in parasite development and identification of novel targets for antimalaria drugs or transmission blocking
  • Development of high-sensitivity assay for Plasmodium infection and others

Biography

Dr. Mu received his M.D. from Shanxi Medical University, China, and his Ph.D. from Saitama Medical School, Japan. He then joined NIAID Division of Intramural Research in 2000 and served as visiting fellow, research fellow, and staff scientist. Now, Dr. Mu is an associate scientist in the office of the Chief of Laboratory of Malaria and Vector Research (LMVR), NIAID. His research mainly focuses on the functional genomics of Plasmodium parasites, including the mechanisms of malaria gene regulation, drug responses, immune evasion, and pathogenesis by applying various approaches, such as genetic mapping and genome-wide association (GWA), genetic manipulation, epigenetic and epitranscriptomic modification. Findings from his research include the genome-wide association study to map the loci associated with P. falciparum resistance to antimalarial drugs, epigenetic regulation of antigenic variation in P. falciparum parasites, epitranscriptomic modification in P. falciparum gene regulations and the development of the high-sensitivity assay for Plasmodium infection.

Dr. Mu serves as the Editorial Board member for journals including Current Genomics, Frontiers in Cell and Developmental Biology, and Journal of Tropical Medicine. Dr. Mu received numerous awards, including NIAID Merit Award and Performance Award.

Publications

Liu M*, Guo G*, Qian P*, Mu J*, Lu B, He X, Fan Y, Shang X, Yang G, Shen S, Liu W, Wang L, Gu L, Mu Q, Yu X, Zhao Y, Culleton R, Cao J, Jiang L, Wellems TE, Yuan J, Jiang C, Zhang Q (2022) 5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes.Proc Natl Acad Sci U S A. Mar 1;119(9):e2110713119. doi: 10.1073/pnas.2110713119.

Mu J, Yu LL, Wellems TE (2020) Sensitive Immunoassay Detection of Plasmodium Lactate Dehydrogenase by Inductively Coupled Plasma Mass Spectrometry. Front Cell Infect Microbiol. Jan 11;10:620419. doi: 10.3389/fcimb.2020.620419.

Xiao B, Yin S, Hu Y, Sun M, Wei J, Huang Z, Wen Y, Dai X, Chen H, Mu J, Cui L, Jiang L (2019) Epigenetic editing by CRISPR/dCas9 in Plasmodium falciparum. Proc Natl Acad Sci U S A. 2019 Jan 2;116(1):255-260. doi: 10.1073/pnas.1813542116.

Mu J, Andersen JF, Valenzuela JG, Wellems TE (2017) High-Sensitivity Assays for Plasmodium falciparum Infection by Immuno-Polymerase Chain Reaction Detection of PfIDEh and PfLDH Antigens.J Infect Dis. Sep 15;216(6):713-722. doi: 10.1093/infdis/jix369.

Jiang L*, Mu J*, Zhang Q, Ni T, Srinivasan P, Rayavara K, Yang W, Turner L, Lavstsen T, Theander TG, Peng W, Wei G, Jing Q, Wakabayashi Y, Bansal A, Luo Y, Ribeiro JM, Scherf A, Aravind L, Zhu J, Zhao K, Miller LH (2013) PfSETvs methylation of histone H3K36 represses virulence genes in Plasmodium falciparum. .Nature. Jul 11;499(7457):223-7. doi: 10.1038/nature12361. 

Mu J, Myers RA, Jiang H, Liu S, Ricklefs S, Waisberg M, Chotivanich K, Wilairatana P, Krudsood S, White NJ, Udomsangpetch R, Cui L, Ho M, Ou F, Li H, Song J, Li G, Wang X, Seila S, Sokunthea S, Socheat D, Sturdevant DE, Porcella SF, Fairhurst RM, Wellems TE, Awadalla P, Su XZ (2010) Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs. Nat Genet. Mar;42(3):268-71. doi: 10.1038/ng.528.

View a complete listing of publications on PubMed.

Tools & Equipment

Sanger sequencing (ABI3730xl) and illumina NextSeq 550 System are available for genotyping, DNA sequencing, whole-genome sequencing and RNA-seq etc.

Section or Unit Name
Malaria Genetics Section
First Name
Jianbing
Last Name
Mu
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Section/Unit: Location
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Program Description
  • Parasites genetic diversity and associated phenotypes, such as antimalarial drug resistance and parasites virulence factors
  • Epigenetic and epitranscriptomic modifications in parasite development and identification of novel targets for antimalaria drugs or transmission blocking
  • Development of high-sensitivity assay for Plasmodium infection and others
  • Multi-omic studies on disease vectors, with a focus on ticks and mosquitoes, aimed at identifying biomarkers and advancing vaccine development
Selected Publications

Lee SK, Crosnier C, Valenzuela-Leon PC, Dizon BLP, Atkinson JP, Mu J, Wright GJ, Calvo E, Gunalan K, Miller LH. Complement receptor 1 is the human erythrocyte receptor for Plasmodium vivax erythrocyte binding protein. Proc Natl Acad Sci U S A. 2024 Jan 30;121(5):e2316304121.

Liu M, Guo G, Qian P, Mu J, Lu B, He X, Fan Y, Shang X, Yang G, Shen S, Liu W, Wang L, Gu L, Mu Q, Yu X, Zhao Y, Culleton R, Cao J, Jiang L, Wellems TE, Yuan J, Jiang C, Zhang Q (2022) 5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes. Proc Natl Acad Sci U S A. Mar 1;119(9):e2110713119.

Xiao B, Yin S, Hu Y, Sun M, Wei J, Huang Z, Wen Y, Dai X, Chen H, Mu J, Cui L, Jiang L (2019) Epigenetic editing by CRISPR/dCas9 in Plasmodium falciparum. Proc Natl Acad Sci U S A. 2019 Jan 2;116(1):255-260.

Mu J, Andersen JF, Valenzuela JG, Wellems TE (2017) High-Sensitivity Assays for Plasmodium falciparum Infection by Immuno-Polymerase Chain Reaction Detection of PfIDEh and PfLDH Antigens. J Infect Dis. Sep 15;216(6):713-722.

Jiang L, Mu J, Zhang Q, Ni T, Srinivasan P, Rayavara K, Yang W, Turner L, Lavstsen T, Theander TG, Peng W, Wei G, Jing Q, Wakabayashi Y, Bansal A, Luo Y, Ribeiro JM, Scherf A, Aravind L, Zhu J, Zhao K, Miller LH (2013) PfSETvs methylation of histone H3K36 represses virulence genes in Plasmodium falciparum. Nature. Jul 11;499(7457):223-7.

Mu J, Myers RA, Jiang H, Liu S, Ricklefs S, Waisberg M, Chotivanich K, Wilairatana P, Krudsood S, White NJ, Udomsangpetch R, Cui L, Ho M, Ou F, Li H, Song J, Li G, Wang X, Seila S, Sokunthea S, Socheat D, Sturdevant DE, Porcella SF, Fairhurst RM, Wellems TE, Awadalla P, Su XZ. Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs. Nat Genet. 2010 Mar;42(3):268-71.

Visit PubMed for a complete publications listing

Additional Information

Tools & Equipment

Dr. Mu oversees the Genomics Core, which is equipped with advanced technologies to facilitate a broad spectrum of genomic and multi-omic studies. These include Sanger sequencing using the ABI3730xl, which provides high-throughput and high-accuracy DNA sequencing for genotyping and targeted DNA analysis. The Illumina NextSeq 550 System enables high-throughput next-generation sequencing (NGS), supporting applications such as whole-genome sequencing, RNA sequencing (RNA-seq), and epigenomics. Additionally, the CosMx Spatial Molecular Imager (SMI) facilitates cutting-edge spatial multiomics analysis, allowing for high-resolution spatial profiling of RNA and protein expression in complex tissues. Together, these platforms provide comprehensive tools for exploring genetic, transcriptomic, and spatial molecular data to address a variety of research questions.

Major Areas of Research
  • Genetic and epigenetic gene regulations in Plasmodium parasites
  • Molecular biology of malaria pathogenesis

Veronique Nussenblatt, M.D, Sc.M., M.H.S

Chief, Infectious Disease Consult Service
Associate Program Director, Infectious Disease Fellowship
Director, NIH Residency Electives Program (REP) and Clinical Electives Program (CEP) for Medical Students

Major Areas of Research

  • COVID-19

Biography

Dr. Nussenblatt received her M.D. from the University of Maryland School of Medicine and completed her internal medicine residency and infectious disease fellowship at the Johns Hopkins University School of Medicine. After completing her training, she joined the Infectious Disease faculty at The Johns Hopkins School of Medicine until she moved to Belgium where she spent two years providing clinical and scientific expertise for the development and implementation of clinical studies within two European clinical trial networks.

Program Description

Dr. Nussenblatt specialized in general infectious diseases as well as managing infections in immunocompromised hosts. She provides diagnostic and therapeutic expertise for the management of infections in patients enrolled in clinical protocols at the NIH. She has a particular interest in COVID-19 in immunocompromised patients. Dr. Nussenblatt provides clinical supervision and training of infectious disease fellows and of residents and medical students rotating on the Infectious Disease Consult Service at the NIH.  

Selected Publications

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Training Programs

Section or Unit Name
Infectious Disease Consult Service
First Name
Veronique
Last Name
Nussenblatt
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Program Description

Dr. Nussenblatt specialized in general infectious diseases as well as managing infections in immunocompromised hosts. She provides diagnostic and therapeutic expertise for the management of infections in patients enrolled in clinical protocols at the NIH. She has a particular interest in COVID-19 in immunocompromised patients. Dr. Nussenblatt provides clinical supervision and training of infectious disease fellows and of residents and medical students rotating on the Infectious Disease Consult Service at the NIH. 

Selected Publications

Suh GA, Lodise TP, Tamma PD, Knisely JM, Alexander J, Aslam S, Barton KD, Bizzell E, Totten KMC, Campbell JL, Chan BK, Cunningham SA, Goodman KE, Greenwood-Quaintance KE, Harris AD, Hesse S, Maresso A, Nussenblatt V, Pride D, Rybak MJ, Sund Z, van Duin D, Van Tyne D, Patel R; Antibacterial Resistance Leadership Group. Considerations for the Use of Phage Therapy in Clinical Practice. Antimicrob Agents Chemother. 2022 Mar 15;66(3):e0207121.

Nussenblatt V, Roder AE, Das S, de Wit E, Youn JH, Banakis S, Mushegian A, Mederos C, Wang W, Chung M, Pérez-Pérez L, Palmore T, Brudno JN, Kochenderfer JN, Ghedin E. Year-long COVID-19 infection reveals within-host evolution of SARS-CoV-2 in a patient with B cell depletion. medRxiv [Preprint]. 2021 Oct 5:2021.10.02.21264267.

Melendez-Munoz R, Marchalik R, Jerussi T, Dimitrova D, Nussenblatt V, Beri A, Rai K, Wilder JS, Barrett AJ, Battiwalla M, Childs RW, Fitzhugh CD, Fowler DH, Fry TJ, Gress RE, Hsieh MM, Ito S, Kang EM, Pavletic SZ, Shah NN, Tisdale JF, Gea-Banacloche J, Kanakry CG, Kanakry JA. Cytomegalovirus Infection Incidence and Risk Factors Across Diverse Hematopoietic Cell Transplantation Platforms Using a Standardized Monitoring and Treatment Approach: A Comprehensive Evaluation from a Single Institution. Biol Blood Marrow Transplant. 2019 Mar;25(3):577-586.

Sigfrid L, Reusken C, Eckerle I, Nussenblatt V, Lipworth S, Messina J, Kraemer M, Ergonul O, Papa A, Koopmans M, Horby P. Preparing clinicians for (re-)emerging arbovirus infectious diseases in Europe. Clin Microbiol Infect. 2018 Mar;24(3):229-239.

Nussenblatt V, Avdic E, Berenholtz S, Daugherty E, Hadhazy E, Lipsett PA, Maragakis LL, Perl TM, Speck K, Swoboda SM, Ziai W, Cosgrove SE. Ventilator-associated pneumonia: overdiagnosis and treatment are common in medical and surgical intensive care units. Infect Control Hosp Epidemiol. 2014 Mar;35(3):278-84.

Visit PubMed for a complete publication listing.

Additional Information

Training Programs

Major Areas of Research
  • COVID-19

Artificial Intelligence (AI)—Integrated Research Facility at Fort Detrick

Artificial intelligence (AI), in its many forms, is applied to infectious disease research at the IRF-Frederick. Primarily focused on medical imaging of preclinical models, state of the art methods are developed, applied to ongoing research and translated to human studies of disease.

NIH Center for Human Immunology, Inflammation, and Autoimmunity Scientific Advisory Board

The CHI Scientific Advisory Boards (SAB) is composed of internationally recognized scientists. The membership of the Scientific Advisory Board reflects the NIH’s research spectrum and are appointed by the Chair of the SAB after consultation with Scientific Directors (SD) from participating institutes. In justified cases, the Scientific Advisory Board – in agreement SD may enlist additional ad hoc experts.

A Bellwether for COVID-19

Publish or Event Date
Research Institution
Harvard Medical School
Short Title
A Bellwether for COVID-19