The Ploegh Lab studies the various tactics that viruses employ to evade our immune responses, and the ways in which our immune system--both innate and adaptive--distinguishes friend from foe. The findings have illuminated not only host-pathogen interactions, but also aspects of protein quality control, an area to which the lab continues to apply chemistry-based strategies. Other technologies include new methods for protein labeling and for the production of mouse models by somatic cell nuclear transfer (“cloning”).
Ploegh and his laboratory reported new mechanisms by which dendritic cells sense the presence of antigens and instruct the immune response, using Class II MHC-eGFP knockin mice and live cell imaging. In addition, Ploegh has helped elucidate how products of the major histocompatibility complex (MHC) are assembled and are delivered to the right destination to help an immune response kick in. Herpesviruses such as HCMV evade the immune system by selective destruction of Class I MHC products. A recent innovation is the generation of cloned mice with lymphocytes specific for pathogens such as Toxoplasma and herpesviruses, using the technique of somatic cell nuclear transfer.
Ploegh and his coworkers have emphasized the generation of the chemical tools with which to probe the ubiquitin-proteasome system. These tools include bacterially derived transacylases (sortases) as convenient tools for protein modification. A contributor to over 400 papers, Ploegh taught at Harvard Medical School where he headed the school’s immunology program (1997-2005). Prior to that, Ploegh was a Professor of Biology at MIT, working in the Center for Cancer Research (now David H. Koch Institute for Integrative Cancer Research).
Mashayekhi M, Sandau MM, Dunay IR, Frickel EM, Khan A, Goldszmid RS, Sher A, Ploegh HL, Murphy TL, Sibley LD, Murphy KM. CD8α(+) Dendritic cells are the critical source of interleukin-12 that controls acute infection by Toxoplasma gondii tachyzoites. Immunity. 2011 Aug 26;35(2):249-259.
Klemm EJ, Spooner E, Ploegh HL. The dual role of ancient ubiquitous protein 1 (AUP1) in lipid droplet accumulation and ER protein quality control. J Biol Chem. 2011 Aug 20.
Esteban A, Popp MW, Vyas VK, Strijbis K, Ploegh HL, Fink GR. Fungal recognition is mediated by the association of dectin-1 and galectin-3 in macrophages. Proc Natl Acad Sci U S A. 2011 Aug 8.
Avalos AM, Ploegh HL. Competition by inhibitory oligonucleotides prevents binding of CpG to C-terminal TLR9. Eur J Immunol. 2011 Jul 18.
Carette JE, Guimaraes CP, Wuethrich I, Blomen VA, Varadarajan M, Sun C, Bell G, Yuan B, Muellner MK, Nijman SM, Ploegh HL, Brummelkamp TR. Global gene disruption in human cells to assign genes to phenotypes by deep sequencing. Nat Biotechnol. 2011 May 29;29(6):542-6.
Buti L, Spooner E, Van der Veen AG, Rappuoli R, Covacci A, Ploegh HL. Helicobacter pylori cytotoxin-associated gene A (CagA) subverts the apoptosis-stimulating protein of p53 (ASPP2) tumor suppressor pathway of the host. Proc Natl Acad Sci U S A. 2011 May 31;108(22):9238-43.
Popp MW, Ploegh HL. Making and breaking peptide bonds: protein engineering using sortase. Angew Chem Int Ed Engl. 2011 May 23;50(22):5024-32.