Qiang Pan-Hammarström

Regulation of immunoglobulin class switch recombination in human B cells

The aim of our project is to try to understand the complex molecular mechanisms involved in DNA editing, repair and recombination during immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM).

Our project requires access to patients with various defects in the DNA repair pathways. Many of these diseases are exceedingly rare. However, through worldwide collaboration, we have obtained samples from many of the diagnosed patients. We are also refining the existing screening methods and developing novel methods, that will allow identification of additional patients both with recognized and new diseases caused by mutations in DNA repair pathways.

We have developed a series of PCR-based assays to study in vivo generated CSR junctions and the pattern of mutations introduced in the immunoglobulin variable region genes in human B cells, allowing us to characterize CSR and SHM in patients with immunodeficiency due to defect(s) in DNA repair/recombination. Novel in vitro CSR assays, based on GFP expression, allowing quantitative measurement of substrate recombination, are also being developed. In addition, we have initiated an evolutionary analysis of the function and structure of activation-induced deaminase, an essential molecule involved both in CSR and SHM, aiming to identify CSR specific-cofactor(s). Combining these approaches, we will be able to define the DNA repair pathways involved in CSR and SHM.

Finally, we hope to be able to address the question whether illegitimate CSR events are associated with predisposition to lymphomagenesis in patients with immunodeficiency/DNA repair defect(s), by analyzing the CSR induced chromosomal breaks and translocations in these patients. A large-scale sequencing project, using the next generation sequencing platform, has been initiated to characterize the CSRnome in B-cell lymphoma samples.

Our research is supported by the Swedish Research Council (VR), the Swedish Cancer Society (Cancerfonden) and the European Research Council (ERC).

The Qiang Pan-Hammarström Research Group operates at Karolinska Institutet Huddinge, Alfred Nobels Allé 8, level 7, Department of Laboratory Medicine, ("Odontology Building" elevator C)

Group Leader

Professor Qiang Pan-Hammarström

Group Leader
Work:
+46 (0)8 5248 3592
E-mail:
Address:
  • Karolinska Institutet Huddinge,
    Alfred Nobels Allé 8, level 7,
    Department of Laboratory Medicine,
    ("Odontology Building" Elevator C)

Group Members

Noel Filipe de Miranda

Postdoc Researcher
Phone:
+46 8 5248 3595
E-mail:
Address:
  • Visiting Address:
    Karolinska Institutet
    Department of Laboratory Medicine
    Alfred Nobels Allé 8, level 7
    Huddinge

Georgia Kokaraki

Postdoc Researcher
Phone:
+46 (0)8 5248 3590
E-mail:
Address:
  • Visiting Address:
    Karolinska Institutet
    Department of Laboratory Medicine
    Alfred Nobels Allé 8, level 7
    Huddinge

Chenglin Wu

Postdoc Researcher
Phone:
+46 (0)8 5248 3546
E-mail:
Address:
  • Visiting Address:
    Karolinska Institutet
    Department of Laboratory Medicine
    Alfred Nobels Allé 8, level 7
    Huddinge

Likun Du

Postdoc Researcher
Phone:
+46 (0)8 5248 3591
E-mail:
Address:
  • Visiting Address:
    Karolinska Institutet
    Department of Laboratory Medicine
    Alfred Nobels Allé 8, level 7
    Huddinge

Andrea Björkman

PhD Student
Phone:
+46 (0)8 5248 3591
E-mail:
Address:
  • Visiting Address:
    Karolinska Institutet
    Department of Laboratory Medicine
    Alfred Nobels Allé 8, level 7
    Huddinge

Konstantinos Georgiou

PhD Student
Phone:
+46 (0)8 5248 3591
E-mail:
Address:
  • Visiting Address:
    Karolinska Institutet
    Department of Laboratory Medicine
    Alfred Nobels Allé 8, level 7
    Huddinge
From the left: Chenglin Wu, Likun Du, Cornelia Rosner, Noel de Miranda, Andrea Björkman, Georgia Kokaraki. Center: Ning Wang

The Qiang Pan-Hammarström Research Group

Last modified by: Camilla Wernersson 2012-10-29