Targeting HSP90 dimerization via the C terminus is effective in imatinib-resistant CML and lacks the heat shock response.
AuthorsBhatia S, Diedrich D, Frieg B, Ahlert H, Stein S, Bopp B, Lang F, Zang T, Kröger T, Ernst T, Kögler G, Krieg A, Lüdeke S, Kunkel H, Rodrigues Moita AJ, Kassack MU, Marquardt V, Opitz FV, Oldenburg M, Remke M, Babor F, Grez M, Hochhaus A, Borkhardt A, Groth G, Nagel-Steger L, Jose J, Kurz T, Gohlke H, Hansen FK, Hauer J
JournalBlood
PubMed ID29724897
'Heat shock protein 90 (HSP90) stabilizes many client proteins, including the BCR-ABL1 oncoprotein. BCR-ABL1 is the hallmark of chronic myeloid leukemia (CML) in which treatment-free remission (TFR) is limited, with clinical and economic consequences. Thus, there is an urgent need for novel therapeutics that synergize with current treatment approaches. Several ... More
Reduced levels of cytosolic DNA sensor AIM2 are associated with impaired cytokine responses in healthy elderly.
AuthorsWang Q, Westra J, van der Geest KS, Moser J, Bijzet J, Kuiper T, Lorencetti PG, Joosten LA, Netea MG, Heeringa P, Brouwer E, Boots AM
JournalExp Gerontol
PubMed ID26944367
Human aging is associated with remodeling of the immune system. While most studies on immunosenescence have focused on adaptive immunity, the effects of aging on innate immunity are not well understood. Here, we investigated whether aging affects cytokine responses to a wide range of well-defined pattern recognition receptor (PRR) ligands, ... More
Serum cytokine measurements and biological therapy of psoriasis - Prospects for personalized treatment?
AuthorsSolberg SM, Sandvik LF, Eidsheim M, Jonsson R, Bryceson YT, Appel S
JournalScand J Immunol
PubMed ID30307657
Psoriasis is an immune-mediated disease where the IL-23/Th17 axis as well as TNF comprise main targets of biological therapy. Immune profiling has so far not been embraced as a clinical tool. We aimed to investigate relationships between individual serum cytokine levels in 40 psoriasis patients before and after receiving biological ... More
Single-cell profiling of peanut-responsive T cells in patients with peanut allergy reveals heterogeneous effector T
AuthorsChiang D, Chen X, Jones SM, Wood RA, Sicherer SH, Burks AW, Leung DYM, Agashe C, Grishin A, Dawson P, Davidson WF, Newman L, Sebra R, Merad M, Sampson HA, Losic B, Berin MC
JournalJ Allergy Clin Immunol
PubMed ID29408715
The contribution of phenotypic variation of peanut-specific T cells to clinical allergy or tolerance to peanut is not well understood.
Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting.
AuthorsRotolo A, Caputo VS, Holubova M, Baxan N, Dubois O, Chaudhry MS, Xiao X, Goudevenou K, Pitcher DS, Petevi K, Kachramanoglou C, Iles S, Naresh K, Maher J, Karadimitris A
Upregulated type I interferon responses in asymptomatic COVID-19 infection are associated with improved clinical outcome.
AuthorsMasood KI, Yameen M, Ashraf J, Shahid S, Mahmood SF, Nasir A, Nasir N, Jamil B, Ghanchi NK, Khanum I, Razzak SA, Kanji A, Hussain R, E Rottenberg M, Hasan Z
JournalSci Rep
PubMed ID34824360
Understanding key host protective mechanisms against SARS-CoV-2 infection can help improve treatment modalities for COVID-19. We used a blood transcriptome approach to study biomarkers associated with differing severity of COVID-19, comparing severe and mild Symptomatic disease with Asymptomatic COVID-19 and uninfected Controls. There was suppression of antigen presentation but upregulation ... More
Novel mutations in the WFS1 gene are associated with Wolfram syndrome and systemic inflammation.
AuthorsPanfili E, Mondanelli G, Orabona C, Belladonna ML, Gargaro M, Fallarino F, Orecchini E, Prontera P, Proietti E, Frontino G, Tirelli E, Iacono A, Vacca C, Puccetti P, Grohmann U, Esposito S, Pallotta MT
JournalHum Mol Genet
PubMed ID33693650
Mutations in the WFS1 gene, encoding wolframin (WFS1), cause endoplasmic reticulum (ER) stress and are associated with a rare autosomal-recessive disorder known as Wolfram syndrome (WS). WS is clinically characterized by childhood-onset diabetes mellitus, optic atrophy, deafness, diabetes insipidus and neurological signs. We identified two novel WFS1 mutations in a ... More
Characterization of an engineered live bacterial therapeutic for the treatment of phenylketonuria in a human gut-on-a-chip.
Engineered bacteria (synthetic biotics) represent a new class of therapeutics that leverage the tools of synthetic biology. Translational testing strategies are required to predict synthetic biotic function in the human body. Gut-on-a-chip microfluidics technology presents an opportunity to characterize strain function within a simulated human gastrointestinal tract. Here, we apply ... More