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.

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.

Genetic Factors in Atherosclerosis, #00-I-0143

A Phase I Study of Mozobil in the Treatment of Patients with WHIMS, #09-I-0200

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.

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).

• 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.

Phase I Open-Label Study of Safety and Immunogenicity of Ad4-HIV Envelope Vaccine Vectors in Healthy Volunteers: NCT03878121

A CoHOrt Clinical, Viral and ImmuNOlogic Monitoring Study of People Living with Retroviral Infection in Liberia (HONOR)

Leukapheresis to Obtain Plasma or Lymphocytes for Studies of HIV-infected Patients, Including Long-term Non-progressors: NCT00029445

• 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

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.

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.

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

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.

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.  

• 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.

Infectious Diseases Fellowship

NIH Residency Electives Program (REP)

Clinical Electives Program (CEP)