Immunotherapy – Robert Harris' research group

We aim to apply novel therapies derived from experimental studies into the human clinical setting.

News highlights

Publications

Selected publications

PhD theses

PhD students with Bob as Main Supervisor

Keying Zhu 2023-05-17
Deciphering and fine-tuning of myeloid cells in CNS demyelinating conditions

Jinming Han 2021-02-19
Repopulation of a microglia-depleted central nervous system : molecular characterization during homeostasis and disease 
After leaving the lab began as a Post-doctoral fellow, Capital Hospital, Bejing, China

Melanie Pieber 2019-04-26
Myeloid cells in experimental neuropathologies
After leaving the lab began as a Post-doctoral fellow at UCB, Vancouver, Canada

Harald Lund 2018-06-01    
Regulation of microglia and monocyte function by the cytokine TGF-beta
After leaving the lab began as a Post-doctoral fellow at UCLA, USA

Eyglo Gudmundsdottir 2017-11-30 
The effects of parenting a child diagnosed with cancer : distress, resilience and vital exhaustion. Living with death in your face

Chao Sun 2017-04-28 
Studies of b-AP15 : a novel inhibitor of proteasome deubiquitinase activity  

Andreas Warnecke 2016-06-14
Post-translational modifications of myelin oligodendrocyte glycoprotein in CNS autoimmunity
After leaving the lab began at a Biotechnology company in Stockholm

Roham Parsa   2015-06-12
Innate regulation of the adaptive immune system during autoimmunity
After leaving the lab began as a Post-doctoral fellow at Rockefeller, USA

Sohel Mia 2014-04-11
Myeloid cells in autoimmune diseases
After leaving the lab began as a Post-doctoral fellow at KI

Åsa Andersson 2006-01-27
Macrophages : As central inflammatory mediators and as targets for therapeutic interventions   

After leaving the lab began as a Post-doctoral fellow at UCLA, USA

Maja Wållberg 2005-05-04
Modulation of immune responses in experimental autoimmune encephalomyelitis   
After leaving the lab began as a Post-doctoral fellow at Cambridge University, UK

Judit Wefer 2004-09-17
Studies of cellular pathogenesis in experimental autoimmune encephalomyelitis
After leaving the lab was Employed by Grants Office, KI

Khairul-Bariah Abdul-Majid  2002-01-11
Pathogenesis of myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis in DBA/1 mice 
After leaving the lab began as a Post-doctoral fellow at Johns Hopkins University, USA
 

PhD students with Bob as co-supervisor

Caroline DeVisscher 2021-06-03
Characterization and long-term follow-up of Pediatric Acute-onset Neuropsychiatric Syndrome (PANS)              
After completion of PhD continued as a practicing clinician

Oscar Diaz Perez 2021-05-28 - Post-doctoral fellow, USA
Impact of genetic and environmental factors in intestinal inflammation
After completion of PhD began as a Post-doctoral fellow USA

Elena Di Martino 2020-10-02
Neonatal hypoxic ischemic encephalopathy : inflammation and therapies           
After completion of PhD began as a Post-doctoral fellow USA

Eliane Piket 2020-06-12
Immunopathogenesis of multiple sclerosis : big roles for small RNAs

After completion of PhD joined ImmunoIVD AB as an application specialist

Natalia Sherina 2019-12-13
On the origin of ACPA : exploring the role of P. gingivalis in the development of rheumatoid arthritis
After completion of PhD began as a Post-doctoral fellow at KI

Marie N’diaye 2018-03-16
Immunological mechanisms regulating neuroinflammation : a role for C-type lectin receptors and vitamin D
After completion of PhD began as a Post-doctoral fellow at KI

Sabrina Ruhrmann 2017-05-19
Involvement of epigenetic mechanisms in disease inheritance and pathogenesis of Multiple Sclerosis (MS) with a focus on genomic imprinting and DNA methylation in CD4+ T cells
After completion of PhD began as a Post-doctoral fellow at KI

Nataliya Tarasova 2016-06-17
Establishing a proteomics-based monocyte assay to assess differential innate immune responses
After completion of PhD began as a Post-doctoral fellow at KI

Anna Maria Marino 2012-12-07
Experimental combination therapy of brain cancer cell models
After completion of PhD began as a Post-doctoral fellow at KI

Melanie Thessen Hedreul 2012-06-15
Genetic and Immunological Regulation of Neuroinflammation
After completion of PhD continued as a research scientist at Celgene

Elizabeth Jedell 2010-12-17
Polycystic ovary syndrome: Studies of affective symptoms in association with sex steroids and evaluation of electroacupuncture and physical exercise

Alan Gillett 2010-11-19
Genetic and Immunological Mechanisms Regulating Neuroinflammation
After completion of PhD joined Merck Group, Canada

Amennai Beyeen 2010-11-12
Definition of genetic and pathogenic mechanisms regulating neuroinflammation

After completion of PhD joined Novartis, Sweden

Jan Ottervald 2009-11-27
Proteomics in neurological disease
After completion of PhD continued as a research scientist at Astra Zeneca

Anna Ökvist 2009-06-08
Synaptic plasticity in drug abuse disorders : Studies of the human post-mortem brain
After completion of PhD began as a research scientist at KaroBio

Ruxandra Covacu 2008-01-24
Adult neural stem cells in neuroinflammation
After completion of PhD began as a Post-doctoral fellow at KI

Monica Marta 2007-09-25
Gene regulation and immune mechanisms in multiple sclerosis experimental models
After completion of PhD began as a Post-doctoral fellow at Kings College London, UK

Samer Sourial 2005-10-07
Functional studies on the interaction of immunoglobulins with HIV-2 envelope
After completion of PhD began as a Medical student at KI

John Andersson (Docent) 2003-06-04
Experimental chagas disease
After completion of PhD began as a Post-doctoral fellow at NIH, USA

Maha Hamadien 2002-08-29
Parasite signalling and host responses in experimental and human African trypanosomiasis
After completion of PhD began as a Post-doctoral fellow at UCLA, USA

Saad Muhallab 2002-06-14
T cell production of cytokines, neurotrophins and MHC regulation in autoimmune neuroinflammation
After completion of PhD began as a clinician at Linköping Hospital, Sweden

Ahmed Sharafeldin 2001-12-14
Immunological studies in the brain and signaling pathways in experimental African trypanosomiasis
After completion of PhD began as a Post-doctoral fellow at KI

Dan Sunnemark 1998-05-20
Immunopathogenesis of experimental Chagas' disease
After completion of PhD began as a research scientist at Astra Zeneca

Azael Saldana (Docent) 1997-11-19
Immunobiochemical significance of Trypanosoma rangeli in the study of Trypanosoma cruzi
After completion of PhD began as a Post-doctoral fellow at Panama University and later became Professor

Funding

 

Swedish Medical Research Council (VR)

Alltid Litt Sterkere

Neurofonden

Thierry Latran Foundation

Stiftelse Olle Engkvist

Åhlen stiftelse

Ulla Carin Lindquist Foundation 

CancerFonden

Karolinska Institutet KID

 

Staff and contact

Group leader

All members of the group

FAQ

Some frequently asked questions

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.

Photo gallery

Bob Harris co-supervisors
Image gallery
+ 12 images

Our research - what we do

Immunotherapy

The Applied Immunology group is dedicated to investigation of the pathogenesis of incurable diseases affecting the Central Nervous System /CNS), including chronic Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Alzheimer’s disease and Glioblastoma brain tumors. There are currently no effective therapies for any of these diseases and so our primary aim is to develop new therapies for use in these diseases. Through study of experimental diseases,our ultimate aim is to apply this knowledge to the human clinical situation. 

We conduct a strongly interconnected research programme aimed at using knowledge gained from projects in basic science to applications in a clinical setting. These aims can be summarised as: 

  • Studying the heterogeneity of microglial function in the CNS 
  • Developing myeloid cell-targeted immunotherapies 
  • Development of novel immunotherapies using immunoparticles

Another major aim is the training of PhD students and postdoctoral fellows. We contribute to teaching in the undergraduate programs for Allergy, Immunology & Inflammation, Neuroscience and Biomedicine. Students and clinicians are welcome to conduct projects in the laboratory. The research laboratory is located in the Centre for Molecular Medicine (CMM) at the Karolinska Hospital. Within CMM, we collaborate with research groups in rheumatology, immunology, cell biology and other disciplines. We are also engaged in active collaborations with research groups at MTC, Huddinge Hospital and several international institutions.

Research projects

  • Personalised myeloid cell therapy for treatment of chronic neuroinflammatory diseases 
  • Microglial depletion and repopulation treatment of neurodegenerative diseases 
  • Immunotherapy in neurological diseases using immunoparticles 

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 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 neurodegenerative disease states. We use both macrophages and microglia-like cells in our studies of microglia replacement therapy.

Scientific Hypothesis addressed: Adoptive transfer of amniotic epithelial cells will be an effective treatment for neurodegenerative disease states. The stem-like immunoregulatory properties of AECs that are usually used to protect unborn infants are now applied to immunomodulate neurodegenerative disease processes, and in particular modulation of microglia function.

Team leader

A team leader operates as an additional leadership support to our research group leader and conducts its own research.
 

Sebastian Lewandovski

Profile image

Sebastian Lewandowski

Teamleader - Neurovascular injury and neurodegeration

Team members (Sebastian Lewandowski's team)

News & Media

 

Video links

Fighting Brain Tumors and Alzheimers 
https://youtu.be/MKKhGbUa6-c
 

#followup with Robert Harris - some intreresting news
https://youtu.be/JFxMMrDsOYY
 

Introducing Neurotech2040
https://youtu.be/VR35CRd3Tb0
 

Nationella Dekanmötet i Lund 2019
https://youtu.be/RZbu44CbWCA
 

7th Trials Methodology Symposium 2021, Prof. Robert Harris
https://youtu.be/GrXr7tAnWI0

 

Media

Nature Careers podcast: 10th February 2023.
Showing the love as a science leader: the emotional side of empowering and inspiring others https://www.nature.com/articles/d41586-023-00417-2


Professor Bob Harris – with an award and a sword
https://news.ki.se/professor-bob-harris-with-an-award-and-a-sword

Robert Harris (Director of post graduation studies at Karolinska Institute and President of ORPHEUS) visited the Escola de Medicina
https://twitter.com/icvs_uminho/status/1045672561080750082

https://he-il.facebook.com/dsa.karolinska/photos/5209863485714396/

Reflections and visions for modernization: why doctoral education needs TECH
https://www.qqi.ie/sites/default/files/2022-10/10.20-11.05%2019%20Oct%20-%20%20Bob%20Harris%20-%20Breakout%20-%20Doctoral%20Education%20-%20Hogan%20Suite.pdf

Latest news

News 2023

News archive

2021-2022

2015 - 2020

 

Research Highlights

Perivascular fibroblast cells contribute to ALS neurodegeneration

Team leader Sebastian Lewandowski led a study that identified a rare brain cell type called ’perivascular fibroblast’ that becomes activated in early, asymptomatic stages of amyotrophic lateral sclerosis (ALS). These fibroblasts remodel the structure of brain vessels by depositing the COL6A1 and SPP1 proteins. These protein biomarkers in ALS patient plasma indicate short survival with stronger effects than the classical neurofilament biomarkers.

 

The study presents a cell in the brain blood vessels as a possible explanation for the varying disease course in ALS. The results highlight a previously unknown relationship between the nervous and vascular systems in ALS.
Photo: Grafik: Sebastian Lewandowski.

Månberg A, Skene N, Sanders F, Trusohamn M, Remnestål J, Szczepińska A, Aksoylu IS, Lönnerberg P, Ebarasi L, Wouters S, Lehmann M, Olofsson J, Von Gohren Antequera I, Domaniku A, De Schaepdryver M, De Vocht J, Poesen K, Uhlén M, Anink J, Mijnsbergen C, Vergunst-Bosch H, Hübers A, Kläppe U, Rodriguez-Vieitez E, Gilthorpe JD, Hedlund E, Harris RA, Aronica E, Van Damme P, Ludolph A, Veldink J, Ingre C, Nilsson P, Lewandowski SA.
Altered perivascular fibroblast activity precedes ALS disease onset. Nature Medicine 2021 27:640–646
 

A new therapeutic target for modulating the harmful effects of demyelination

By employing loss-of-function and gain-of-function studies, PhD student Keying Zhu revealed that microglial function is highly affected in terms of the functional activity of the transient receptor potential vanilloid 1 (TRPV1). Global activation of TRPV1 drives microglia to a demyelinating state and enhances microglial phagocytosis. TRPV1 is thus a candidate target for immunotherapy in neurodegenerative diseases.

Research highlights Bob Harris

Jinxian Sun, Ke-ing Zhu, Yumeng Wang, Dan-ie Wang, Mi-zhen Zhang, Heela Sarlus, Irene Benito-Cuesta, Xiaoqiang Zhao, Zaofeng Zou, Qingyang Zhong, Yi Feng, Shuai Wu, Yanqing Wang, Robert A Harris, Jun Wang. Activation of TRPV1 receptor facilitates myelin repair following demyelination via the regulation of microglial function. Acta Pharmacologica Sinica 44 (4), 766-779

 

Specifically inhibiting microglial activation reduces neuroinflammation:

PhD student Keying Zhu devised and conducted this project, in which he developed a new form of immunotherapy. Through drug screening of pre-existing drugs, Keying identified Topetecan as an inhibitor of Topisomerase 1, and proved this protein had a role in neuroinflammation. Myeloid-specific TOP1 inhibition using TopoGami significantly suppresses the inflammatory response in microglia and mitigates MS-like disease progression.

flow diagram, Bob Harris research group

Zhu K, Wang Y, Sarlus H, Geng K, Nutma E, Sun J, Kung SY, Bay C, Han J, Min JH, Benito-Cuesta I, Lund H, Amor S, Wang J, Zhang XM, Kutter C, Guerreiro-Cacais AO, Högberg B, Harris RA. Myeloid cell-specific topoisomerase 1 inhibition using DNA origami mitigates neuroinflammation. EMBO Rep. 2022 23(7):e54499.

 

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.

Nature, Bob Harris research group
Nature

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.

PyTMs, Bob Harris research group
PyTMs

 

 

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:

Nit, Bob Harris research group
Nit

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 form the foundation of our concept of myeloid cell therapy.

In the first 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:

Diabetes, Bob Harris research group
Diabetes

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 chronic disease phase, a timepoint again difficult to modulate in previous attempts by other research groups:

Glia, Bob Harris research group
Glia

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:

TGFb, Bob Harris research group
TGFb

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 during the 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:

BAFF, Bob Harris research group
BAFF

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