ROBERT HARRIS GROUP
Applied Immunology and immunotherapy
IMAGINE a time when we could end the suffering of individuals with chronic inflammatory diseases.
Realising that dream is what we must do NOW,
BECAUSE we have the knowledge, drive and vision to make it happen.
We conduct a strongly interconnected research programme aimed at using knowledge gained from projects in basic science to applications in a clinical setting. We focus on understanding why chronic inflammatory diseases occur, and then devise ways to prevent or treat them.
We are a small group working to conduct translational medicine in the true sense of the definition – starting in the lab and ending in the clinic. We believe that even though we are a small lab, we can still make a valuable contribution.
Lab philosophy: We believe that good research has good research training as its foundation. As it takes more energy to frown than to smile, we make the lab an environment where everyone likes to be.
Current funding sources
Alltid Litt Sterkere
KI KID funding
We are primarily interested in understanding the pathogenesis of incurable, chronic disease states of the Central Nervous System, including ALS, MS, Alzheimer's disease and glioma brain tumors.
HOW CAN WE TREAT OR CURE THE DISEASES?
There is currently no cure for the diseases we study, and existing medications are only partly effective.
Our main interest is thus on developing new strategies to reduce or abrogate disease symptoms.
We focus on using the body’s own myeloid cells as a means of treating the same individual through ‘personalised cell therapy’ or by targeting these cells for immunomodulation.
Scientific Hypothesis addressed: Adoptive transfer of pre-activated myeloid cells will be an effective treatment for inflammatory/neurodegenerative disease states (LINK).
Scientific Hypothesis addressed: siRNA targeting of specific genes will be an effective treatment for inflammatory/neurodegenerative disease states.
Scientific Hypothesis addressed: Specific depletion of antigen-specific T cells that drive autoimmune diseases will be an effective treatment for autoimmune diseases with defined antigen specificities
Scientific Hypothesis addressed: Post-translational modification of self proteins makes them autoantigenic (LINK).
Understanding CNS niche occupancy by microglia and macrophages in health and disease:
In the first of two studies led by PhD student Harald Lund we developed a novel model of microglia depletion using diptheria toxin expressed under the CX3CR1 receptor, which is highly expressed by microglia. The CNS did not allow the permanent depletion of its myeloid cells, and thus blood-circulating monocytes were accepted into the empty niche and adapted to the new environment. The characterization of this process was described in the first Nature Communications paper. We then depleted TGFbeta receptor signaling on the infiltrating monocytes, and this led to development of a novel neurodegenerative disease state that we characterised in the second Nature Immunology paper.
Lund H, Pieber M, Parsa R, Han J, Grommisch D, Ewing E, Kular L, Needhamsen M, Butovsky O, Jagodic M, Zhang X-M, Harris RA: Competitive repopulation of an empty microglial niche gives rise to functionally distinct subsets of microglia-like cells. Nature Communications 2018 9:4845
Lund H, Pieber M, Parsa R, Grommisch D, Ewing E, Kular L, Han J, Zhu K, Nijsen J, Hedlund E, Needhamsen M, Ruhrmann S, Ortlieb Guerreiro Cacais A, Berglund R, Forteza MJ, Ketelhuth DFJ, Butovsky O, Jagodic M, Zhang X-M, Harris RA: Fatal demyelinating disease is induced by monocyte-derived macrophages in the absence of TGF-β signaling. Nature Immunology 2018;19:1-7
The consequences of post-translational modifications for autoantigens:
In the first of these 3 studies led by PhD student Andreas Warnecke he devised, wrote a script for and further developed a programme for visualising the 3-d form of post-translationally modified proteins using known structures, a resource which is openly available online.
Warnecke A, Sandalova T, Achour A, Harris RA: PyTMs: A useful PyMOL plugin for modeling common post-translational modifications. BMC Bioinformatics 2014;15:370
In subsequent studies Andreas determined that the functional consequences of PTM modification of autioantigens determined the molecular interactions with myeloid cells, and that the immunological outcome was MHC-dependent:
Warnecke A, Musunuri S, N'diaye M, Sandalova T, Achour A, Bergquist J, Harris RA: Nitration of MOG diminishes its encephalitogenicity depending on MHC haplotype. Journal of Neuroimmunology 2017;303:1-12
Warnecke A, Abele S, Musunuri S, Bergquist J, Harris RA: Scavenger Receptor A mediates the clearance and immunological screening of MDA-modified antigen by M2 type macrophages. NeuroMolecular Medicine 2017;9:463-479
Immunosuppressive macrophage cell therapy modulates development of autoimmune disease:
In a series of studies we developed a robust protocol for induction of potently immunosuppressive macrophages that for the fundament to our concept of myeloid cell therapy.
In the fiorst of these studies PhD student Roham Parsa demonstrated a significant prevention of development of Type 1 diabetes following macrophage cell therapy. The effect was even more dramatic considering that the therapy was initiated directly before disease onset, a timepoint proven difficult to immunomodulate in most other therapy studies in the NOD Type 1 Diabetes model:
Parsa R, Andresen P, Gillett A, Mia S, Zhang X-M, Mayans S, Holmberg D, Harris RA: Adoptive Transfer of Immunomodulatory M2 Macrophages Prevents Type 1 Diabetes in NOD Mice. Diabetes 2012;61:2881-92
Postdoc Xingmei Zhang conducted a similar study in a model of neuroinflammation, and likewise could demonstrate a significant reduction in development of paralytic disease, even when the therapy was initiated during the chrinic disease phase, a timepoint again difficult to modulate in previous attempts by other research groups:
Zhang X-M, Lund H, Mia S, Parsa R & Harris RA: Adoptive transfer of cytokine-induced immunomodulatory adult microglia attenuates experimental autoimmune encephalomyelitis in DBA/1 mice. Glia 2014;62:5 804-817
Importantly, PhD student Sohel Mia could then use the same stimulation protocol to prove that human macrophages from autoimmune patients were efficient at inhibiting their own pathogenic T cells in in vitro assays, providing a translational proof-of-concept.
Mia, S, Warnecke A, Zhang X-M, Harris RA: An optimized protocol for human M2 macrophages using M-CSF and IL-4/IL-10/TGF-β yields a dominant immunosuppressive phenotype. Scandanavian Journal Immunology 2014;79:305-14
One of the hallmark cytokines produced by the immunosuppressive macrophages is TGFβ, and the importance of this cytokine in maintaining cellular homeostasis was exemplified in PhD student Roham Parsa's study which revealed a worsening of neuroinflammation in the absence of TGFβ signaling:
Parsa R, Lund H, Tosevski I, Zhang XM, Malipiero U, Beckervordersandforth J, Merkler D, Prinz M, Gyllenberg A, James T, Warnecke A, Hillert J, Alfredsson L, Kockum I, Olsson T, Fontana A, Suter T, Harris RA: TGFβ regulates persistent neuroinflammation by controlling Th1 polarization and ROS production via monocyte-derived dendritic cells. Glia 2016;64:1925-37
A novel principle for improved humoral vaccination
In this study PhD student Roham Parsa set out to generate a macrophage-deficient mouse strain, but instead developed a neutrophil-deficient mouse strain. Through characterising the respective roles of neutrophils in early and late phases of immune activation, we could conclude that manipulation of neutrophil numbers at the site of inoculation would be a means of generating enhanced antibody responses to the injected substance:
Parsa R, Lund L, Georgoudaki A-M, Zhang X-M, Ortlieb Guerreiro-Cacais A, Grommisch D, Warnecke A, Croxford AL, Jagodic M, Becher B, Karlsson MCI, Harris RA: BAFF-secreting neutrophils drive plasma cell genesis during emergency granulopoiesis. Journal of Experimental Medicine 2016;213:1537-53
Professor Robert A. Harris
Professor Robert A. Harris (Bob) was born in Harpenden in Southern UK in 1966. He conducted a Bsc.Hons undergraduate degree at Portsmouth Polytechnic, majoring in Parasitology in 1987. PhD studies at University College London studying innate immune agglutinins in Schistosoma host snail species with Terry Preston and Vaughan Southgate as supervisors culminated with a thesis defence in early 1991. A 2.5 year postdoc at the London School of Hygiene & Tropical Medicine in Paul Kaye’s research group ensued, with focus on understanding the intracellular fate of Leishmania spp. protozoans in macrophages. Bob was awarded a Wellcome Trust postdoctoral fellowship that permitted his relocation to the Karolinska Institutet (Stockholm, Sweden) in the spring of 1994. A postdoc period was spent split between the labs of Anders Örn and Tomas Olsson, in which he studied Trypanosoma cruzi and Trypanosoma bruceii protozoan proteins. Bob became an Associate Professor at the Karolinska Institutet in 1999, heralding his establishment as a PI. Bob started to work with autoimmune diseases in 1996 and began study of therapy using live parasite infections or parasite molecules. His research group has developed autoantigen-specific vaccines, defined the effects of post-translational biochemical molecules on autoantigenicity and developed a macrophage adoptive transfer therapy that prevents pathogenesis in several experimental disease models. He became Professor of Immunotherapy in Neurological Diseases in 2013. In recent years research focus has centred on understanding the immunopathogenesis of incurable neurodegenerative diseases, with particular emphasis on development of immunotherapies directed at microglial cells as potential therapeutic paradigms.
Bob Harris CV July 2020
A brief research history
Characterization of autoaggressive and protective immunological mechanisms in mouse and rat EAE models
We have developed a novel experimental model of multiple sclerosis in the DBA/1 mouse, (MOG-induced Experimental Autoimmune Encephalomyelitis (MOG-EAE)) which is a severe disease model that exhibits the pathology most resembling human pathology of all mouse models (Link to Publication). We have dissected the immunological pathogenesis of MOG-EAE in this model by making use of various knockout mice (impossible to do in the rat models as yet). We have studied the relative contribution to pathogenesis of T cell subsets and determined that CD8+ T cells play a significant role through use of DBA/1 knockout mice lacking functional CD4+ or CD8+ T cells (Link to Publication). We have demonstrated the importance of B cells by using B cell deficient DBA/1 mice (Link to Publication), which led to further fine dissection using DBA/1 knockout mice lacking specific Fcgamma receptors (Link to Publication) and with consequent deficient B cell functions. These were the first studies to indicate that Fcgamma receptors are vital for MOG-EAE pathogenesis, and as these receptors are expressed on Antigen Presenting Cells (APCs) such as macrophages and microglia, they indicate that APC function may be equally important in pathogenesis as the T and B lymphocyte requirements we have already characterized. We additionally studied the role of FLIP in MOG-EAE in DBA/1 mice using retroviral-induced over-expression, which led to disease exacerbation (Link to Publication).
With respect to cells involved in pathogenesis or protection, we have characterized a difference in the proinflammatory activities of macrophages in susceptible and resistant rat strains (Link to Publication). Signaling pathways in macrophages from different rat strains differed after activation with a variety of stimuli, and this was associated with differential production of the pro-inflammatory mediators nitric oxide and IL-23. We continue this base characterization of APC functionality, including comparative studies of macrophages, dendritic cells and microglia in both mice and rats, with focus on the intracellular ion transporter Nramp1. We have also defined the respective roles of Th1 and Th17 encephalitogenic T cells in neuroinflammation during MOG-EAE (Link to Publication) and have more recently confirmed immune gene products in rat MOG-EAE to be the same as in human MS (Link to Publication), including more detailed analysis of the role of TNFa regulation (Link to Publication) and IL-22 (Link to Publication).
What makes an autoantigen a target for immune attack?
We study post-translational modification of autoantigens, as we believe that these inflammation-induced events are what changes a self protein from being unrecognized by the immune system to become an autoantigen capable of inducing autoimmune disease.
We have been able to demonstrate that when MOG is oxidised through aldehydation, it becomes more immunogenic and promotes a more severe disease when immunized into DBA/1 mice (Link to Publication). The structural alterations induced through this modification are subtle, but the resultant effects on immunogenicity are great.
Development of novel immunotherapies for treatment of autoimmune diseases
We design and test novel therapeutic interventions for modulation of rodent autoimmune models, with the intention of innovative technology transfer to treatment of patient groups.
Our efforts to date have yielded a vaccine formulation that completely protects against development of MOG-EAE, and the mechanism attributed to this effect is in part due to induction of Tr3 regulatory T cells (Link to Publication). In addition, we have been able to demonstrate that live parasite infections reduce development of autoimune disease (Link to Publication) and that adoptive transfer of specifically activated immunosuppressive macrophages can also reduce disease development in settings of both neuroinflammation (Link to Publication) and Type 1 Diabetes (Link to Publication). We discovered that selective neutrophil depletion exacerbates B cell antibody responses (Link to Publication), which provides a novel principle for increasing vaccination efficiency when antibody responses are desirable.
Microglial depletion and repopulation therapy
We have studied the consequence of prolonged depletion of microglial depletion in the CNS, and how monocytes adapt to become microglial-like cells on entry into a depleted CNS (Link to Publication). When TGFb signalling is prohibited on these infiltrating monocytes a fatal demyelinating disease develops through selective destruction of motor neurons (Link to Publication). This led us to hypothesize that selective depletion and repopulation of tge CNS with in vitro-derived, pre-activated microglia-like cells might hold promise as an effective immunotherapy for neurodegenerative diseases (Link to Publication).
Do you have a PhD position available?
I have had good success in securing faculty (KID) funding for several PhD students, and these positions are advertised at KI Jobb. Social skills, ability to work collaboratively and a genuine interest in our work are all prerequisites for being accepted. A 4-year PhD training should not be something you do because you have nothing better to do – you should have a vocation for science and in particular the science we do. I am happy to receive enquiries from people fulfilling these requirements.
Do you have a Masters project position available?
I usually have one Masters project student per term working together with one of my PhD students. You are welcome to contact me and to express an interest in working within one of the projects described in the lab profile. Social skills, ability to work collaboratively and a genuine interest in our work are all prerequisites for being accepted.
Do you have a postdoc position available?
Funding for postdocs is often the hardest type of funding to secure. If you are interested in working in my lab you are welcome to contact me and submit a CV and a statement describing your specific research interests. If funding is available in the lab then great. If not you will be expected to provide your own funding or strategy for securing financing.
Do you accept volunteers?
I do not accept volunteers. If you are making a valuable contribution to my lab you will get paid for your efforts.
Media and Documents
To be updated
To be updated
22-10-2020 The Norwegian foundation Alltid Litt Sterkere donates 500 000 SEK to our research efforts.
18-10-2020 Bob gives an address and a reseacrh lecture during the 130th Anniversary symposium of Qilu Hospital, Shangdong, China.
17-09-2020 Jinming's latest research findings are published in IJMS.
07-07-2020 Bob reviews a Collaborative Research Centre application for DFG (Germany).
29-06-2020 Sebastian receives €198700 in research funding from the Thierry Latran Foundation.
07-05-2020 Bob holds a research webinar within 'IWF Framtidens Medicin.'
06-05-2020 Keying's latest research findings are published in Glia.
01-06-2020 Keying receives a KI travel grant (14 000 SEK) to attend a Cold Spring Harbour conference on Glia in Japan.
15-01-2020 Bob gives an invited research seminar at the Heinrich Heine University in Dusselsdorf, Germany.
18-12-2019 AlzheimerFonden awards 500 000 SEK to our research efforts.
06-12-2019 Bob evaluates the doctoral programme at the University of Beira Interior, Covilha, Portugal.
22-11-2019 Former PhD students Harald Lund and Melanie Pieber receive their PhD diplomas and doctor's hats from Bob during the official ceremony at City Hall (see photos).
12-11-2019 CancerFonden awards 2 400 000 SEK for our research efforts in glioma.
11/12-11-2019 Bob teaches during the Eatris 'Translation Medicine Explained (TMEX)' course in Barcelona, Spain.
21-10-2019 Bob visits Shangdong University in Jinan, China.
18-10-2019 Bob presents at the CSC fair in Bejing, China.
03/04-10-2019 PhD student Jinming Han presents his poster at the annual Karolinska Inflammation and Immunology network (KiiM) retreat at Lidingö.
30-09-2019 PhD student Jinming Han is appointed as a section editor for Annals of Translational Medicine (impact factor: 3.689 in 2018) from October 2019 to September 2020.
27/28-09-2019 Bob gives a plenary scientific lecture and a plenary educational lecture as well as leading a workshop on supervision at the FEBS-HDBMB2019 Croatian Society of Biochemistry annual conference in Louvran, Croatia.
21-09-2019 Bob attends the annual Alltid Litt Stekere meeting in Oslo, Norway, acting as a panel member to discuss ALS with the public. Alltid Litt Stekere generously grants us 250 000 NOK for our research programme.
11-13-09-2019 PhD student Jinming presents his poster at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis ( ECTRIMS ) in Stockholm, Sweden.
24-06-2019 PhD student Jinming Han receives a free registration as a travel grant to attend The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2019 at Stockholm, Sweden.
03-06-06-2019 PhD students Jinming Han and Keying Zhu present posters at The Second Conference on Molecular Mechanisms of Inflammation at Trondheim, Norway. Jinming Han receives a travel grant from the SWIMM
07-06-2019 HjärnFonden awards 600 000 SEK to our research efforts.
23-24-05-2019 Bob attends the EUROLIFE 20th anniversary annual meeting in Leiden, Holland.
26-04-2019 PhD student Melanie Pieber successfully defends her thesis with Prof Andreas Schlitzer (Bonn, Germany) as faculty opponent.
12-04-2019 Bob gives a research seminar at BMC, Uppsala University, Sweden.
08-10-04-2019 Bob gives a talk about 'Doctoral Education i Europe and the ORPHEUS vision' at the National meeting of Medical Deans in Lund, Sweden.
21-23-03-2019 Bob gives a talk about 'Current and Futire Trends in Doctoral Eduction - Global Trends' at the 14th ORPHEUS conference in Dublin, Ireland.
15-03-2019 Jinming successfully conducts his halftime control.
13-02-2019 Bob gives a KI Discovers research seminar at Nobel Forum.
01-02-2019 Bob teaches a supervisor training workshop at University College Dublin, Ireland.
30-01-2019 Bob conducts a 4hr supervisor workshop at the Julich Research Centre, Julich, Geremany.
17-01-2019 Bob participates in plenary discussion panel at EUA-CDE thematic workshop on 'Inter-institutional collaboration' at Vrije University, Amsterdam, Holland.
01-01-2019 Bob assumes the role of Academic Vice-President for Doctoral Education at Karolinska Institutet.
24-12-2018 Keying's latest research article is published in Brain Research.
14-12-2018 AlzheimerFonden awards 700 000 SEK to our research efforts.
13-12-2018 BarnCancerFonden awards 1 000 000 SEK to our research efforts.
12-11-2018 The Board of Doctoral Education at KI awarded Bob PhD student funding (KID).
23-10-2018 Harald’s latest research article is accepted for publication in Nature Communications.
23-10-2018 Bob teaches at Luleå University at the supervisor training session on ILOs and feedback.
08-10-2018 Bob gives plenary lectures as part of the ‘Grand Rounds’ and ‘Graduate Programe Administrators Conference’ during a 3-day visit to Vanderbilt University, Nashville, USA.
20->21-09-2018 Melanie, Jinming and Keying present posters at the annual KiiM conference at Lidingö.
15-09-2018 Bob conducts a 6hr supervisor workshop at the School of Medicine, University of Minho, Covilha, Portugal.
22-08-2018 Jinming’s latest review article is accepted for publication in Glia.
15-06-2018 Bob conducts a 4hr supervisor workshop at the Department of Clinical Medicine, University of Beira Interior, Covilha, Portugal.
12-06-2018 PhD students Jinming Han and Keying Zhu each receive an EFIA-EJI Travel Grant in order to attend the 5th European Congress of Immunology (ECI 2018) in Amsterdam in Septemebr 2018.
11-06-2018 Bob examines PhD student Alba Manresa Arraut at the University of Copenhagen as faculty opponent.
01-06-2018 PhD student Harald Lund successfully defends his thesis with Prof Martin Guilliams (Ghent, Belgium) as faculty opponent.
23-26-05-2018 Bob gives a talk about giving and receiving professional feedback at the 13th ORPHEUS conference in Reykjavik, Iceland.
09-05-2018 PhD student Harald Lund nails up his thesis.
03-05-2018 The Norwegian foundation Alltid Litt Sterkere donates 200 000 SEK to our research efforts.
26-04-2018 Bob gives a talk about lessons learned in reserach at the CMM Day 2018
16->20-04-2018 Bob teaches at the ENLIGHTEN/C-COMEND course in Translational Medicine in Berlin, Germany.
13-04-2018 Bob gives a plenary lecture at the FEBS/Biochemistry Society conference in Chester, UK
16-03-2018 PhD student Marie N’diaye that Bob is co-supervisor for successfully defends her PhD thesis.
10-03-2018 Harald’s latest scientific masterpiece is accepted for publication in Nature Immunology.
09-03-2018 Bob teaches a supervisor training workshop at University College Dublin, Ireland.
06-03-2018 PhD student Melanie Pieber receives travel grants from KI fonder and Gålöstiftelsen to support her attendance at ISNI 2018 in Brisbane, Australia.
26-01-2018 Bob examines KI PhD student Twana Alkasalias as a thesis commitee member.
18-01-2018 Bob examines KI PhD student Johanna Snäll as a thesis commitee member.
13-12-2017 AlzheimerFonden awards the group 200 000 SEK research funds for 2018.
13-12-2017 Bob examines Stockholm University PhD student Sachie Kanatani as a thesis commitee member.
11-12-2017 Bob examines KI PhD student Lora Deuitch as a thesis commitee member.
08-12-2017 Melanie conducts her halftime control review.
06-12-2017 Bob gives a double lecture on microglia-astrocyte biology to Biomedicine Masters students.
02-12-2017 Bob is examiner as faculty opponent for PhD student Cecilia Hagert at Turku University, Finland.
30-11-2017 PhD student Eyglo Gudmundsdottir successfully defends her thesis with Dr Ullakarin Nyberg (KI) as faculty opponent.
24-11-2017 Bob examines KI PhD student Maria Teresa Fernandez as a thesis commitee member.
22-11-2017 Results from the Employee Survey for our group were very favourable:
20-11-2017 After 9 years in the lab we say goodbye to Roham and wish him well for his postdoc at the Rockefeller University, New York, USA.
09->10-11-20117 Bob attends the STINT project executive steering board retreat in Stockholm.
18->20-10-2017 The group attends the SSI congress in Stockholm, with Harald giving an oral presentation, and Melanie, Roham and Jinming presenting posters.
09->13/10-2017 Bob teaches at and Melanie attends the C-COMEND course in Translational Medicine in Berlin, Germany.
02-10-2017 Bob gives a lecture on macrophage biology to Biomedicine Masters students.
26-9-2017 Bob teaches at Luleå University at the supervisor training session on ILOs and feedback.
21->23-9-2017 Bob presents the groups latest research at the EMDS congress in Madrid, Spain.
7-9-2017 Bob gives a plenary lecture at the ‘New Horizons in Biochemistry & Molecular Biology Education congress at the Weizmann Institute of Science, Revohot, Israel.
21->23-08-2017 Bob teaches supervisor training to 27 researchers from the Helmholtz association in Germany.
15-08-2017 Bob’s first article about doctoral education in accepted for publication in FEBS Open Bio.
06-08-2017 Andreas’s MDA-MOG article is accepted for publication in Neuromolecular Medicine.
28-07-2017 Harald & Melanie’s review article is accepted for publication in Frontiers in Aging.
12-06-2017 Jinming Han & Xing-Mei’s review article is accepted for publication in Molecular Brain.
06-06-2017 Bob attends the C-COMEND consortium annual meeting in Hannover.
05-6-2017 Hjärnfonden awards the group 1 000 000 SEK in research funds for 2017-2019.
04->06-05-2017 Bob attends the ORPHEUS annual congress in Klaipeda, Lithuania and particpates in a debate entitled ‘Only excellence versus more equal opportunities in PhD education.’
28-4-2017 PhD student Chao Sun defends his thesis ‘Studies of b-AP15 – a novel inhibitor of proteasome deubiquitinase activity‘ with Petter Höglund as faculty opponent.
20->22-3-2017 Bob gives a lecture at the Universitas 21 annual meeting in Dublin, Ireland.
15-3-2017 Bob teaches at Luleå University at the supervisor training session on ILOs and feedback.
16->17-02-2017 Bob hosted the C-COMEND consortium for their annual meeting.
21-12-2016 AlzheimerFonden awards the group 400 000 SEK research funds for 2017.
07-12-2012 Jinming Han is registered as a PhD student in the Department of Clinical Neuroscience.
14-12-2016 The Board of Doctoral Education at KI awarded Bob PhD student funding (KID).
12-12-2016 Harald Lund gives a research seminar at MTC, KI on microglial depletion models.
28->30-11-2016 Bob teaches at and co-arranges a course in Translational Medicine within the EU-funded C-COMEND consortium in Manchester, UK.
23-11-2016 PhD student Andreas Warnecke’s latest study is published online in Journal of Neuroimmunology.
10-11-2016 Bob gives a lecture at Uppsala University in the Immune, Gene & Cell Therapy postgraduate course.
25-10-2016 Bob teaches a double session for supervisors at Luleå Technical University, Sweden, in ‘Outcome-based doctoral training’ and ‘Professional responsibility of supervisors.’
17-10-2016 KI fonder grants research funds to the Harris group for both 2016 & 2017.
14-10-2016 Xing-Mei Zhang, Melanie Pieber, Harald Lund and Jinming Han attend the KiiM annual retreat at Sånga Säby, Ekerö, Sweden, and Harald wins the ‘Best Poster’ prize.
7-10-2016 Bob attends the AMSE annual congress in Prague, Czechoslovakia and gives a plenary lecture ‘Why the Karolinska does (not) need clinical PhDs.’
3-10-2016 Jinming Han joins the Applied Immunology & Immunotherapy group.
21-09-2016 PhD student Melanie Pieber and postdoc Roham Parsa present their work at the EMDC conference in Amsterdam. Melanie received an SLB travel award.
12-09-2016 Bob attends the Vitae Researcher Development International Conference 2016 in Manchester, UK, and gives a plenary lecture ‘Supervisor development: pedagogies, engagement and evaluation.’
02-08-2016 PhD students Roham Parsa and Harald Lund’s latest study is published online at Glia.
25-07-2016 PhD students Roham Parsa and Harald Lund publish an article in The Journal of Experimental Medicine.
17-06-2016 Bob attends the 9th EUA-CDE Annual Meeting, Tarragona, Spain, and is an invited speaker in a roundtable discussion‘Quality or Quantity? What is the dilemma in research education?’ at the June 2016.
14-06-2016 PhD student Andreas Warnecke successfully defends his thesis with Prof Christoph Binder (Vienna) as faculty opponent.
09->12-03-2016 Bob attends the 11th ORPHEUS conference in Köln, Germany and gives two plenary lectures, ‘The ORPHEUS mission – aims and challenges’ & ‘What happens when you train supervisors – the KI experience’.
22-02-2016 Bob gives a plenary lecture at the workshop ‘Better research through PhD education in health science’ in Istanbul, Turkey
16-09-2015 Bob gives a lecture about Macrophage Biology to PhD students during the Basic Immunologytraining course.
09->10-09-2015 Bob evaluates Doctoral Education at Örebro University on behalf of UKÄ.
03-09-2015 Bob evaluates Doctoral Education at the University of Iceland on behalf of ORPHEUS.
24->25-08-2015 Bob evaluates INCA award applications on behalf of the Swedish Medical Research Council.
12-06-2015 PhD student Roham Parsa successfully defends his thesis with Assoc Prof Jordi Ochando (New York) as faculty opponent.
11-05-2015 Bob gives a double plenary lecture at Aarhus University, Denmark, ‘Professional conduct of Supervisors’ and ‘Outcome-based research training’
21-04-2015 Professor Frank Heppner from the Charite-Universitätsmedizin, Berlin, Germany visits us on the initiative of the Swedish National Research school in Inflammation. Frank will discuss PhD student Harald Lund’s project regarding pathogeneiss of Alzheimer’s disease and give Harald constructive feedback about both scientific progress and future plans.
16->18-04-2015 Bob attends the 10th ORPHEUS conference in Belgrade, Serbia and gives a plenary lecture ‘Why, How and What Impact? – Experiences of Doctoral Training at Karolinska Institutet.’
13-04-2015 Bob attends the CMM junior faculty retreat and gives a lecture about ‘Professional conduct in the workplace.’
16-03-2015 Postdoc Xing-mei Zhang receives 1.2M SEK from BarnCancerFonden for her project ‘Myeloid cell therapy for treatment of malignant glioblastoma’.
17-03-2015 Postdoc Xing-mei Zhang receives a 4-year research assistant position starting 1-1-2015 from NBCNS.
01-01-2015 PhD student Andreas Warnecke receives 100,000 SEK for his project ‘Post-translational modifications of myelin antigens in pathogensis and therapy of MS’ from Stiftelsen Neurofonden.
05-12-2014 PhD student Andreas Warnecke’s latest research paper is published online in BMC Bioinformatics.
ion of self proteins makes them autoantigenic (LINK).
PhD theses from the lab
PhD students with Bob as main supervisor:
Melanie Pieber 2019-04-26
After leaving the lab began as a Post-doctoral fellow at UCB, Vancouver, Canada
Harald Lund 2018-06-01
After leaving the lab began as a Post-doctoral fellow at UCLA, USA
Eyglo Gudmundsdottir 2017-11-30
Chao Sun 2017-04-28
Andreas Warnecke 2016-06-14
After leaving the lab began at a Biotechnology company in Stockholm
Roham Parsa 2015-06-12
After leaving the lab began as a Post-doctoral fellow at Rockefeller, USA
Sohel Mia 2014-04-11
After leaving the lab began as a Post-doctoral fellow at KI
Åsa Andersson 2006-01-27
After leaving the lab began as a Post-doctoral fellow at UCLA, USA
Maja Wållberg 2005-05-04
After leaving the lab began as a Post-doctoral fellow at Cambridge University, UK
Judit Wefer 2004-09-17
After leaving the lab was Employed by Grants Office, KI
Khairul-Bariah Abdul-Majid 2002-01-11
After leaving the lab began as a Post-doctoral fellow at Johns Hopkins University, USA
PhD students co-supervised by Bob:
Eliane Piket 2020-06-12
Marie N’diaye 2018-03-16
After completion of PhD began as a Post-doctoral fellow at KI
Sabrina Ruhrmann 2017-05-19
After completion of PhD began as a Post-doctoral fellow at KI
Nataliya Tarasova 2016-06-17
After completion of PhD began as a Post-doctoral fellow at KI
Anna Maria Marino 2012-12-07
After completion of PhD began as a Post-doctoral fellow at KI
Melanie Thessen Hedreul 2012-06-15
After completion of PhD continued as a research scientist at Celgene
Elizabeth Jedell 2010-12-17
Alan Gillett 2010-11-19
After completion of PhD joined Merck Group, Canada
Amennai Beyeen 2010-11-12
After completion of PhD joined Novartis, Sweden
Jan Ottervald 2009-11-27
After completion of PhD continued as a research scientist at Astra Zeneca
Anna Ökvist 2009-06-08
After completion of PhD began as a research scientist at KaroBio
Ruxandra Covacu 2008-01-24
After completion of PhD began as a Post-doctoral fellow at KI
Monica Marta 2007-09-25
After completion of PhD began as a Post-doctoral fellow at Kings College London, UK
Samer Sourial 2005-10-07
After completion of PhD began as a Medical student at KI
John Andersson (Docent) 2003-06-04
After completion of PhD began as a Post-doctoral fellow at NIH, USA
Maha Hamadien 2002-08-29
After completion of PhD began as a Post-doctoral fellow at UCLA, USA
Saad Muhallab 2002-06-14
After completion of PhD began as a clinician at Linköping Hospital, Sweden
Ahmed Sharafeldin 2001-12-14
After completion of PhD began as a Post-doctoral fellow at KI
Dan Sunnemark 1998-05-20
After completion of PhD began as a research scientist at Astra Zeneca
Azael Saldana (Docent) 1997-11-19
After completion of PhD began as a Post-doctoral fellow at Panama University and later became Professor
Berglund R , Ortlieb Guerreiro-Cacais A , Z Adzemovic M , Zeitelhofer M , Lund H , Ewing E, Ruhrmann S , Nutma E, Parsa R , Thessen-Hedreul M , Amor S , Harris RA , Olsson T , Jagodic M. Microglial autophagy-associated phagocytosis is essential for recovery from neuroinflammation. Sci Immunol. 2020 Oct 16;5(52):eabb5077. PubMed
Han J, Zhu K, Zhou K, Hakim R, Sankavaram SR, Blomgren K, Lund H, Zhang XM, Harris RA. Sex-Specific Effects of Microglia-Like Cell Engraftment during Experimental Autoimmune Encephalomyelitis. Int J Mol Sci. 2020 17;21(18):6824 PubMed
Carlström KE, Zhu K, Ewing E, Krabbendam IE, Harris RA, Mendanha Falcão A, Jagodic M, Castelo-Branco G, Piehl F. Glutathione S-transferase 4α is a key regulator of oligodendrocyte differentiation and remyelination in models of multiple sclerosis, by reducing Fas/Caspase-8 pathway activity. Nature Communications 2020 11(1):4071 PubMed
Tsuji S, di Martino E, Mukai T, Tsuji S, Murakami T, Harris RA, Blomgren K, Åden U. Aggravated brain injury in microglia depleted male mice after neonatal hypoxic ischemia. Journal of Neuroinflammation 2020 17:111 PubMed
Zhu K, Pieber M, Blomgren K, Zhang X-M, Harris RA, Lund H. Absence of microglia or presence of peripherally derived macrophages do not affect tau pathology in young or old hTau mice. Glia 2020 68:1466-1478 PubMed
N'diaye M, Brauner S, Flytzani S, Kular L, Warnecke A, Adzemovic MZ, Piket E, Min JH, Edwards W, Mela F, Choi HY, Magg V, James T, Linden M, Reichardt HM, Daws MR, van Horssen J, Kockum I, Harris RA, Olsson T, Guerreiro-Cacais AO, Jagodic M. C-type lectin receptors Mcl and Mincle control development of multiple sclerosis-like neuroinflammation. Journal of Clinical Investigation 2020 130:838–852 PubMed
Di Martino E, Bocchetta E, Tsujia S, Mukai T, Harris RA, Blomgren K, Ådén U. Defining a therapeutic window for neuroprotection and glia modulation by caffeine during neonatal hypoxia-ischemia. Molecular Neurobiology 2019 57:2194–2205 PubMed
Gromark C, Harris RA, Wickström R, Horne AC, Silverberg M, Serlachius E, Mataix-Cols D. Establishing a Pediatric Acute-onset Neuropsychiatric Syndrome Clinic: Baseline clinical features of the PANS cohort at Karolinska Institutet. Journal of Child and Adolescent Psychopharmacology 29:625-633 PubMed
Tang Q, Gheorghe KR, Zhang X-M, Lindroos E, Helene Alexanderson MLT, Wick C, Bruton M, Fernandes-Cerqueira C, Harris RA, Nennesmo I, Lundberg IE. Features of repeated muscle biopsies and phenotypes of monocytes in paired blood samples and clinical long-term response to treatment in patients with idiopathic inflammatory myopathy – a pilot study. In Press, Clinical and Experimental Rheumatology PubMed
Lippitz BE, Harris RA. Translational Concept of Immuno-Radiobiology. Radiotherapy and Oncology 2019 140:116-124 PubMed
Yang T, Xu G, Newton PT, Chagin AS, Mkrtchian S, Carlström M, Zhang X-M, Harris RA, Cooter M, Berger M, Maddipati KR, Akassoglou K, Terrando N. Maresin 1 attenuates neuroinflammation in a mouse model of perioperative neurocognitive disorders. British Journal of Anaesthesia 2018 122:350-360 PubMed
Zhu K, Sun J, Kang Z, Zouab Z, Wu X, Wanga Y, Wu G, Harris RA, Wang J. Repurposing of omeprazole for oligodendrocyte differentiation and remyelination. Brain Research 2019 1710:33-42 PubMed
Lund H, Pieber M, Parsa R, Han J, Grommisch D, Ewing E, Kular L, Needhamsen M, Butovsky O, Jagodic M, Zhang X-M, Harris RA: Competitive repopulation of an empty microglial niche gives rise to functionally distinct subsets of microglia-like cells. 2018 Nature Communications 9:4845 PubMed
Han J, Zhu K, Zhang X-M, Harris RA. Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders. 2018 Glia 67:217-231 PubMed
Wallmann T, Zhang X-M, Wallerius M, Bolin S, Joly A-L, Sobocki C, Leiss L, Jiang Y, Bergh J, Andersson J, Holland EC, Enger PØ, Swartling FJ, Uhrbom L, Miletic H, Harris RA, Rolny C. Microglia induce PDGFRB expression in glioma cells to enhance their migratory capacity. 2018 iScience, 9:71-83 PubMed
Obeed OAA, Vaali-Mohamed M-A , Alkhayal KA, Traiki TAB, Zubaidi AM, Arafah M, Harris RA, Khan Z, Hamadien Abdulla M. Interleukin 17 and colorectal cancer risk in Middle East: Gene polymorphisms and expression. 2018 Cancer Management and Research 10:2653–2661 PubMed
Lund H, Pieber M, Parsa R, Grommisch D, Ewing E, Kular L, Han J, Zhu K, Nijsen J, Hedlund E, Needhamsen M, Ruhrmann S, Ortlieb Guerreiro Cacais A, Berglund R, Forteza MJ, Ketelhuth DFJ, Butovsky O, Jagodic M, Zhang X-M, Harris RA: Fatal demyelinating disease is induced by monocyte-derived macrophages in the absence of TGF-β signaling. 2018 Nature Immunology 19:1-7 PubMed
Warnecke A, Abele S, Musunuri S, Bergquist J, Harris RA. Scavenger Receptor A mediates the clearance and immunological screening of MDA-modified antigen by M2 type macrophages. 2017 NeuroMolecular Medicine 9:463-479 PubMed
Sackmann V, Ansell A, Sackmann C, Lund H, Harris RA, Hallbeck M, Nilsberth C. Anti-inflammatory (M2) macrophage media reduce transmission of oligomeric amyloid-beta in differentiated SH-SY5Y cells 2017 Neurobiology of Aging 60:173-182 PubMed
Lund H, Pieber M, Harris RA. Lessons learned about neurodegeneration from microglia and monocyte depletion studies. 2017 Frontiers in Aging Neuroscience 9:234 PubMed
Barnett JV, Harris RA, Mulvany MJ. A comparison of best practices for doctoral training in the European and North American continents. 2017 FEBS Open Bio 7:1444-1452 PubMed
Han J, Harris RA, Zhang X-M. An updated assessment of microglia
depletion: current concepts and future directions. 2017 Molecular Brain 10:25 PubMed
Yang T, Zhang X-M, Tarnawski L, Peleli M, Zhuge Z, Terrando N, Harris RA, Olofsson P, Larsson E, Persson AEG, Lundberg JO, Weitzberg E, Carlstrom M. Dietary nitrate attenuates renal ischemia-reperfusion injuries by modulation of immune responses and reduction of oxidative stress. 2017 Redox Biology 13:320-330 PubMed
Warnecke A, Musunuri S, N’diaye M, Sandalova T, Achour A, Bergquist J, Harris RA. Nitration of MOG diminishes its encephalitogenicity depending on MHC haplotype. J Neuroimmunology 2016 303:1-12 PubMed
Han W, Umekawa T, Zhou K, Zhang X-M, Harris RA, Zhu C, Blomgren K. Cranial irradiation induces transient microglial response with specific gene expression signature and immune profile. OncoTarget 2016 7:82305-82323 PubMed
Hägglöf T, Sedimbi KS, Yates JL, Parsa R, Hauff B, Harris RA, Leadbetter EA, Karlsson MCI. Neutrophils license iNKT cells to regulate self-reactive mouse B cell responses. Nature Immunology 17:1407-1414 PubMed
Parsa R, Lund H, Tosevski I, Zhang XM, Malipiero U, Beckervordersandforth J, Merkler D, Prinz M, Gyllenberg A, James T, Warnecke A, Hillert J, Alfredsson L, Kockum I, Olsson T, Fontana A, Suter T, Harris RA. TGFβ regulates persistent neuroinflammation by controlling Th1 polarization and ROS production via monocyte-derived dendritic cells. Glia 2016 64:1925-37. PubMed
Radenkovic M, Åkesson C, Arvastsson J, Lynch K, Lernmark Å, Harris RA, Agardh CD, Cilio C. Altered regulatory T-cell phenotype in latent autoimmune diabetes of the adults (LADA). Clinical and Experimental Immunology 2016 186:46-56 PubMed
Tarasova NK, Ytterberg AJ, Lundberg K, Zhang XM, Harris RA, Zubarev RA. Establishing a proteomics-based monocyte assay to assess differential innate immune activation responses. J Proteome Res.2016 15:2337-45 PubMed
Parsa R, Lund L, Georgoudaki A-M, Zhang X-M, Ortlieb Guerreiro-Cacais A, Grommisch D, Warnecke A, Croxford AL, Jagodic M, Becher B, Karlsson MCI, Harris RA. BAFF-secreting neutrophils drive plasma cell genesis during emergency granulopoiesis. J Exp Med 2016 213:1537-53 PubMed
Georgoudaki A-M, Prokopec K, Hellqvist E, Boura V, Östling J, Sohn S, Harris RA, Rantalainen M, Klevebring D, Sund M, Fuxe J, Rolny C, Li F, Ravetch, Karlsson MCI. Reprogramming tumor associated macrophages by antibody targeting inhibits cancer progression and metastasis. Cell Reports 2016 15:2000-2011 PubMed
Schmidt A, Zhang X-M, Joshi RN, Iqbal S, Wahlund C, Gabrielsson S, Harris RA*, Tegnér J*. Human macrophages induce CD4+Foxp3+ regulatory T cells via binding and re-release of TGF-β. Immunol & Cell Biol 2016 PubMed
Yao G, Wang P, Luo XD, Yu TM, Harris RA, Zhang XM. Meta-analysis of association between Helicobacter pylori infection and multiple sclerosis. Neurosci Lett. 2016;620:1-7 PubMed
N’diaye M, Warnecke A, Flytzani S, Abdelmagid N, Ruhrmann S, Olsson T, Jagodic M*, Harris RA*, Guerreiro-Cacais AO*. Rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3L exhibit distinct phenotypical and functional characteristics. J Leukoc Biol. 2016;99:437-46. PubMed
Mills CD, Lenz LL, Harris RA. A breakthrough: Macrophage-directed cancer immunotherapy. Cancer Research 2016;76:3 PubMed
Lippitz B, Harris RA. Cytokine Patterns in Cancer Patients: A Review of the Correlation Between Interleukin 6 and Prognosis. OncoImmunology 2016 11;5:e1093722 PubMed
Mills CD, Harris RA, Ley K. Macrophage Polarization: Decisions That Affect Health. Clin Cell Immunol.2015;6:5 pii: 364. PubMed
Tarasova N., Ytterberg A., Lundberg K, Harris RA, Zubarev R. Proteomics reveals synergetic effects of activation and attachment in monocyte differentiation into macrophages. J Proteome Research 2015;14:3940−3947 PubMed
Yang T, Gao X, Sandberg M, Zollbrecht C, Zhang X-M, Hezel M, Liu M, Peleli M, Lai EN, Harris RA, Persson AE, Fredholm BB, Jansson L, Carlström M. Abrogation of adenosine A1 receptor signaling improves metabolic regulation in aging and obesity. Diabetologia 2015 58:1610-20 PubMed
Wang J, Cao Z, Zhang XM, Nakamura M, Sun M, Hartman J, Harris RA, Sun Y, Cao Y. Novel mechanism of macrophage-mediated metastasis revealed in a zebrafish model of tumour development. Cancer Res. 2015 Jan 15;75(2):306-15 Pubmed
Zhang X-M., Lund H., Mia S., Parsa R., Harris RA. Adoptive transfer of cytokine-induced immunomodulatory adult microglia attenuates experimental autoimmune encephalomyelitis in DBA/1 mice. Glia. 2014 ;62(5):804-17 Pubmed
Scheffel J, Regen T, Van Rossum D, Seifert S, Ribes S, Nau R, Parsa R, Harris RA, Boddeke HW, Chuang HN, Pukrop T, Wessels JT, Jürgens T, Merkler D, Brück W, Schnaars M, Simons M, Kettenmann H, Hanisch UK. Toll-like receptor activation reveals developmental reorganization and unmasks responder subsets of microglia. Glia. 2012;60:1930-43 Pubmed
Fransson M., Piras E., Burman J., Nilsson B., Essand M., Lu B., Harris RA., Magnusson PU., Brittebo E., Loskog AS. CAR/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery. J Neuroinflammation. 2012; 30;9:112 Pubmed
Parsa R., Andresen P., Gillett A., Mia S., Zhang X-M., Mayans S., Holmberg D., Harris RA. Adoptive Transfer of Immunomodulatory M2 Macrophages Prevents Type 1 Diabetes in NOD Mice. Diabetes 2012 61:2881-92. 28. Pubmed
Harris RA & Amor S. Sweet and Sour – Oxidative and carbonyl stress in neurological disorders. CNS Neurol Disord Drug Targets 2011; Pubmed
Gillett A, Marta M, Jin T, Tuncel J, Leclerc P, Nohra R, Lange S, Holmdahl R, Olsson T, Harris RA, Jagodic M. TNF production in macrophages is genetically determined and regulates inflammatory diseases. J Immunol 2010;185;442-450. Pubmed
Eriksson F, Tsagozis P, Lundberg K, Parsa R, Mangsbo SM, Persson MA, Harris RA, Pisa P. Tumor-specific bacteriophages induce tumor destruction through activation of tumor-associated macrophages. J Immunol 2009;182:3105-3111. Pubmed
Stromnes IM, Cerretti LM, Liggitt D, Harris RA, Goverman JM. Differential regulation of central nervous system autoimmunity by T(H)1 and T(H)17 cells. Nat Med 2008;14:337-342. Pubmed
Andersson A, Covacu R, Sunnemark D, Danilov AI, Dal Bianco A, Khademi M, Wallstrom E, Lobell A, Brundin L, Lassmann H, Harris RA. Pivotal advance: HMGB1 expression in active lesions of human and experimental multiple sclerosis. J Leukoc Biol 2008;84:1248-1255. Pubmed