Gunilla Karlsson Hedestam Group

Research Description

Genetic basis for B cell recognition and function

Our research focuses on the function of B lymphocytes and qualitative aspects of immunological memory. In several projects, we define anti-viral antibody responses at the clonal level by single-cell sorting memory B cells for sequence analysis of antibody V(D)J transcripts and for isolation and characterization of antigen-specific monoclonal antibodies. We also apply next generation sequencing to analyze expressed immune repertoires and to trace specific antibody lineages to understand their fate and levels of affinity maturation. Because V(D)J gene assignment is a critical first step of lineage tracing, and there is considerable genetic variation in germline V genes/alleles between subjects, we developed a computational tool that allows the generation of individualized germline V gene databases, IgDiscover. This is a major technical advance that will enable the use of individualized germline databases to become a standard element of high-quality immunological studies in both humans and experimental animals. By applying these methods, we obtain highly detailed information about polymorphisms in these genes, allowing us to investigate how the VDJ germline allele content influences the establishment of antigen-specific responses.

Åsa Hidmark, 2007

Opponent: Bruce Beutler
Åsa defended her PhD in 2007 after which she received the Jonas Söderqvist’s Prize for basic research in virology and immunology. Åsa moved on to a post-doctoral position at the University of Heidelberg in Germany, where she is now active as a senior research scientist in the field of immunology and diabetes.

Mattias Forsell, 2008

Opponent: Quentin Sattentau
Mattias defended his PhD in 2008. Part of his doctoral research was carried out at the National Institutes of Health in Washington. After this, he received an Early career investigator AMFAR award for post-doctoral work, which was carried out at Karolinska Institutet. He recently obtained a position as Assistant Professor at Umeå University where he now leads his own research group

Pia Dosenovic, 2012

Opponent: Michael McHeyzer-Williams
Pia defended her PhD in 2012 after which she obtained 3 years of funding from the Swedish Research Council to pursue a post-doc at the Rockefeller University in New York. After several years as a productive member of the Nussenzweig laboratory, she is now back at KI to establish her own research group.

Christopher Sundling, 2012

Opponent: Robin Weiss
Christopher defended his PhD in 2012 and in the last year of his studies he was awarded the Dimitris N. Chorafas Foundation Prize. He subsequently also received the Jonas Söderqvist’s Prize for basic research in virology and immunology and Sven Gard’s prize for best thesis in virology. He then moved on to a post-doc position in the Brink laboratory at the Garvan Institute in Sydney and returned in 2017 to establish his own group at the Department of Medicine, Solna as an Assistant Professor.

Paola Martinez Murillo, 2017

Opponent: Leo Stamatatos
Paola defended her PhD in May of 2017. During her doctoral education she collaborated closely with scientists at the Scripps Research Institute in La Jolla and she spent a month as a visiting student at the Rockefeller University. An additional initiative she took was to teach Immunology to young students in Colombia, two summers in a row. Her Immunity paper published just before her PhD defense received “Best paper of the year” at MTC 2017.

Martina Soldemo, 2017

Opponent: Klaus Überla
Martina defended her PhD in October of 2017 after a productive time as a doctoral student. In addition to her own projects, she was instrumental to many collaborations both within and outside the lab and she contributed enthusiastically to teaching at both the undergraduate and post-graduate level at KI

Ganesh Phad, 2018

Opponent: Stephen Quake
Ganesh defended his PhD in June 2018. During his doctoral studies, he applied a broad set of techniques to study B cell responses and immunization-induced monoclonal antibodies. He was instrumental in setting up Next Generation Sequencing methodology for analyses of antibody repertoires and, together with Martin Corcoran in the group and computational scientist Marcel Martin, developed the broadly applicable IgDiscover tool. Ganesh is currently a post-doctoral fellow in the laboratory of Antonio Lanzavecchia in Switzerland

Néstor Vazquez Bernat, 2019

Opponent: Scott Boyd
Néstor defended his PhD in December 2019 with a thesis focusing on antibody repertoire sequencing and germline gene identification in humans and macaques. He worked closely with his co-supervisor Martin Corcoran to optimize protocols for IgM library production for germline inference and with methods to validate novel alleles identified with the IgDiscover software. His recent paper in Immunity describes a comprehensive database of rhesus and cynomolgus macaque antibody germline alleles, now publicly available (see above). Néstor is currently working with immune repertoire sequencing at ENPICOM in the Netherlands.

Sharesta Khoenkhoen, 2020

Opponent: David Tarlinton
Sharesta defended her PhD thesis in August 2020. During her doctoral studies, Sharesta studied B cell defects in mice lacking an NFkB regulator, IKBNS. The most striking phenotype of IKBNS-deficient mice is that they fail to develop B-1 cells while follicular B cells (FoB cells) develop and are present at normal frequencies. Sharesta demonstrated that while FoB cells present in IKBNS-deficient mice, they are dysfunctional in their ability to differentiate into plasma cells. Sharesta investigated key steps in this process to pinpoint the defect and she is currently staying on in the lab to finish these studies before heading to Berlin for a post-doc position later this year.