We study human B cells in health and disease - Qiang Pan-Hammarström
We focus on two main areas of research:
Primary immunodeficiency and B cell malignancy
Regulation of immunoglobulin class switch recombination in human B cells
This project is aimed at understanding the complex molecular mechanisms involved in DNA editing, repair and recombination during immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM) and their involvement in the pathophysiological processes leading to immunodeficiency, genome instability and cancer development in humans.
Induced pluripotent stems cells a platform for personalized diagnosis and therapy in patients with primary immunodeficiency
The project is aimed at reprogramming the fibroblasts derived from primary immunodeficiency patients into pluripotent stem (iPS) cells and re-differentiating these iPS cells into antibody-producing B cells. If successful, this study will provide a methodological platform for the study of human B cell development and for development of new therapies aiming at editing genes/cells in patients with a variety of other primary immunodeficiency diseases.
Discovery of therapeutic targets in B cell lymphoma by next generation sequencing
The project is aimed at identifying potentially treatable molecular targets in mature B cell lymphomas (with focus on diffuse large B cell lymphoma, follicular lymphoma and mantle cell lymphoma) by applying high-throughput, next generation-sequencing technologies such as whole genome and whole exome sequencing, immune repertoire sequencing, RNA sequencing and single-cell RNA sequencing. The multiomic sequencing data will be further integrated with clinical data as well as functional assays to identify genes/pathways that can be used for disease classification and prediction and for the development of new targeted therapy.
Antibody therapy against COVID-19
The project is aimed at establishing a passive immunotherapy against coronavirus COVID19. To reach this overall goal, we will obtain blood samples from convalescent donors, i.e. people who have recovered from the infection, to isolate antibodies that can be used to prevent and to treat the disease.
X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19.
Asano T, Boisson B, Onodi F, Matuozzo D, Moncada-Velez M, Maglorius Renkilaraj MRL, et al.
Sci Immunol 2021 08;6(62): eabl4348. doi: 10.1126/sciimmunol.abl4348.
Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths.
Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, Manry J, Michailidis E, et al.
Sci Immunol 2021 08;6(62): eabl4340. doi: 10.1126/sciimmunol.abl434
Genetic mechanisms of HLA-I loss and immune escape in diffuse large B cell lymphoma.
Fangazio M, Ladewig E, Gomez K, Garcia-Ibanez L, Kumar R, Teruya-Feldstein J, et al.
Proc Natl Acad Sci U S A 2021 Jun;118(22):
Persistence of SARS-CoV-2-specific B and T cell responses in convalescent COVID-19 patients 6-8 months after the infection.
Sherina N, Piralla A, Du L, Wan H, Kumagai-Braesch M, Andréll J, et al.
Med (N Y) 2021 Mar;2(3):281-295.e4
Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice.
De Gasparo R, Pedotti M, Simonelli L, Nickl P, et al
Nature 2021 Mar; doi: 10.1038/s41586-021-03461-y. Online ahead of print.
Genome-wide mutational signatures revealed distinct developmental paths for human B cell lymphomas.
Ye X, Ren W, Liu D, Li X, Li W, Wang X, et al
J Exp Med 2021 Feb;218(2):e20200573. doi: 10.1084/jem.20200573.
Human T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria.
Yang R, Mele F, Worley L, Langlais D, Rosain J, Benhsaien I, Elarabi H, et al
Cell 2020 Dec 3:S0092-8674(20)31453-7. doi: 10.1016/j.cell.2020.10.046. Online ahead of print.
Pan-cancer analysis of whole genomes.
ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium
Nature 2020 02;578(7793):82-93
Genomic basis for RNA alterations in cancer.
Calabrese C, Davidson NR, Demircioğlu D, Fonseca NA, He Y, et al
Nature 2020 02;578(7793):129-136
Genetic landscape of hepatitis B virus-associated diffuse large B-cell lymphoma.
Ren W, Ye X, Su H, Li W, Liu D, Pirmoradian M, et al
Blood 2018 06;131(24):2670-2681
Reduced immunoglobulin gene diversity in patients with Cornelia de Lange syndrome.
Björkman A, Du L, van der Burg M, Cormier-Daire V, Borck G, Pié J, et al
J. Allergy Clin. Immunol. 2018 01;141(1):408-411.e8
Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency.
Abolhassani H, Edwards ES, Ikinciogullari A, Jing H, Borte S, Buggert M, et al
J. Exp. Med. 2017 01;214(1):91-106
Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency.
Bronson PG, Chang D, Bhangale T, Seldin MF, Ortmann W, Ferreira RC, et al
Nat. Genet. 2016 11;48(11):1425-1429
Genetic basis of PD-L1 overexpression in diffuse large B-cell lymphomas.
Georgiou K, Chen L, Berglund M, Ren W, de Miranda NF, Lisboa S, et al
Blood 2016 06;127(24):3026-34
Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas.
Wu K, Zhang X, Li F, Xiao D, Hou Y, Zhu S, et al
Nat Commun 2015 Dec;6():10131
Aberrant recombination and repair during immunoglobulin class switching in BRCA1-deficient human B cells.
Björkman A, Qvist P, Du L, Bartish M, Zaravinos A, Georgiou K, et al
Proc. Natl. Acad. Sci. U.S.A. 2015 Feb;112(7):2157-62
B cell super-enhancers and regulatory clusters recruit AID tumorigenic activity.
Qian J, Wang Q, Dose M, Pruett N, Kieffer-Kwon KR, Resch W, et al
Cell 2014 Dec;159(7):1524-37
Exome sequencing reveals novel mutation targets in diffuse large B-cell lymphomas derived from Chinese patients.
de Miranda NF, Georgiou K, Chen L, Wu C, Gao Z, Zaravinos A, et al
Blood 2014 Oct;124(16):2544-53
A regulatory role for the cohesin loader NIPBL in nonhomologous end joining during immunoglobulin class switch recombination.
Enervald E, Du L, Visnes T, Björkman A, Lindgren E, Wincent J, et al
J. Exp. Med. 2013 Nov;210(12):2503-13
New facets of antibody deficiencies.
Liadaki K, Sun J, Hammarström L, Pan-Hammarström Q
Curr. Opin. Immunol. 2013 Oct;25(5):629-38
DNA repair genes are selectively mutated in diffuse large B cell lymphomas.
de Miranda NF, Peng R, Georgiou K, Wu C, Falk Sörqvist E, Berglund M, et al
J. Exp. Med. 2013 Aug;210(9):1729-42
Nurture your scientific curiosity early in your research career.
Jagodic M, Stridh P, Gad AK, Paine A, Udekwu KI, Sjöholm LK, et al
Nat. Genet. 2013 Feb;45(2):116-8
Cernunnos influences human immunoglobulin class switch recombination and may be associated with B cell lymphomagenesis.
Du L, Peng R, Björkman A, Filipe de Miranda N, Rosner C, Kotnis A, et al
J. Exp. Med. 2012 Feb;209(2):291-305
Looking for a postdoc position?
Postdoc positions on B cell development, immunogenetics, COVID19 and cancer genetics available.
For details contact: Prof. Pan-Hammarström
DNA sequencing, including whole exome and whole genome sequencing
Gene expression analysis including real time PCR and RNAseq/transcriptome analysis
B and T cell functional assays
Gene editing using the CRISPR/Cas9 system