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.
NIH Merit Award (1992); NIH Director's Award (1994, 1996); NIH Senior Biomedical Research Service (1998); American Society for Clinical Investigation (1992); Association of American Physicians (1997); Pillar of Immunology Award, Journal of Immunology(2009); the Henry Kunkel Society (2006); NIAID Merit Award (2009); NIAID Mentor of the Year Award (2010); Fellow, American Academy of Microbiology (2013); Marie Bonazinga Award of the Society of Leukocyte Biology (2013)
- American Association for the Advancement of Science
- American Society for Clinical Investigation
- American Society of Biochemistry and Molecular Biology
- Association of American Physicians
- American Association of Immunologists
- Society for Leukocyte Biology
- The Henry Kunkel Society
- Cellular Immunology
- Journal of Leukocyte Biology
- Viral Immunology
- Journal of Innate Immunity
- UCSD-Nature Molecule Pages
- Faculty of 1000
- Pontejo SM, Murphy PM. Chemokines act as phosphatidylserine-bound "find-me" signals in apoptotic cell clearance. PLoS Biol. 2021;19(5):e3001259.
- Gao JL, Owusu-Ansah A, Yang A, Yim E, McDermott DH, Jacobs P, Majumdar S, Choi U, Sweeney CL, Malech HL, Murphy PM. CRISPR/Cas9-mediated Cxcr4 disease allele inactivation for gene therapy in a mouse model of WHIM syndrome. Blood. 2023;142(1):23-32.
- 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;10(1):616.
- 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;160(4):686-699.
- 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;380(2):163-170.
Related Scientific Focus Areas
Microbiology and Infectious Diseases
This page was last updated on Monday, August 7, 2023