Meet the people

Prof. Harald Neumann

Prof. Harald Neumann - Coordinator, Unniversitätsklinikum Bonn (UKB)

 

Prof. Harald Neumann is working at the University Hospital of Bonn, Germany

Visit his Lab-webpage or contact him

 

Work performed in PHAGO

“Our group is identifying CD33 receptor-related signalling pathways in microglia and analysing the function of human microglial CD33.”

 

  Interesting readings and/or reviews about our work

1) Publication suggests that TREM2 could have detrimental effects on neurons in aging mice without any disease process.
"TREM2 triggers microglial density and age-related neuronal loss".
Linnartz-Gerlach, B., Bodea, L.G., Klaus, C., Ginolhac, A., Halder, R., Sinkkonen, L., Walter, J., Colonna, M., Neumann, H. (2019). Glia.

 

2) Publication shows in an animal model of retinal laser lesion that local application of soluble polysialic acid  inhibits phagocytes and protects from vascular damage via the CD33-related SIGLEC11 receptor."
"Polysialic acid blocks mononuclear phagocyte reactivity, inhibits complement activation, and protects from vascular damage in the retina."
Karlstetter, M., Kopatz, J., Aslanidis, A., Shahraz, A., Caramoy, A., Linnartz-Gerlach, B., Lin, Y., Lückoff, A., Fauser, S., Düker, K., Claude, J., Wang, Y., Ackermann, J., Schmidt, T., Hornung, V., Skerka, C., Langmann, T., Neumann, H. (2017). EMBO Mol Med
.

 

3) Publication demonstrates in culture that the CD33-related Siglec-E receptor turns down the neurotoxic oxidative burst of murine microglia.
"Microglial CD33-related Siglec-E inhibits neurotoxicity by preventing the phagocytosis associated oxidative burst."
Claude, J., Linnartz-Gerlach, B., Kudinm A.P., Kunz, W.S., Neumann, H. (2013). J Neuroscience

 

Prof. Jochen Walter

Prof. Jochen Walter - Universitätsklinikum Bonn (UKB)

 

Prof. Jochen Walter is working at the University Hospital of Bonn, Germany

Visit his Lab-webpage or contact him

 

Work performed in PHAGO

“We are interested in signalling pathways of TREM2, and the pathophysiological implications for Alzheimer’s disease. In the PHAGO project, we are developing a reporter cell system for TREM2 in order to identify and characterize modulators of TREM2 signalling.”

 

 Interesting readings and/or reviews about our work

1) "This study describes the identification and characterization of a novel TREM2 variant in familial clustering of dementia.”
"A rare heterozygous TREM2 coding variant identified in familial clustering of dementia affects an intrinsically disordered protein region and function of TREM2"
Karsak, M., K. Glebov, M. Scheffold, T. Bajaj, A. Kawalia, I. Karaca, S. Rading, J. Kornhuber, O. Peters, M. Diez-Fairen, L. Frölich, M. Hüll, J. Wiltfang, M. Scherer, S. Riedel-Heller, A. Schneider, M.T. Heneka, K. Fliessbach, A. Sharaf, H. Thiele, M. Lennarz, F. Jessen, W. Maier, C. Kubisch, Z. Ignatova, P.Nürnberg, P. Pastor, J. Walter, Alfredo Ramirez. Hum Mutat (2019)

 

2) "In this study, we demonstrate the proteolytic processing of ephrin B2 by γ-secretase and the functional implications in microglia."
"Intramembranous processing by γ-secretase regulates reverse signaling of ephrin-B2 in migration of microglia"
Kemmerling, N., P. Wunderlich, S. Theil, B. Linnartz-Gerlach, N. Hersch, B. Hoffmann, M.T. Heneka, B. de Strooper, H. Neumann, J. Walter. Glia (2017)

 

3) "This publication shows the importance of intramembrane proteolysis by γ-secretase in the signalling activity of TREM2."
"Functional involvement of γ-secretase in signaling of the triggering receptor expressed on myeloid cells-2 (TREM2)."
Glebov, K., P. Wunderlich, I. Karaca, J. Walter, Neuroinflammation (2016)

 

4) "This review summarized the knowledge on TREM2 and its implication in neurodegenerative diseases.”
"Triggering receptor expressed on myeloid cells 2: A molecular link between neuroinflammation and neurodegeneration"
Walter, J (J Biol. Chem. (2016)

 

5)"This study shows the identification of ectodomain shedding and intramembrane cleavage of TREM2"
"Sequential proteolytic processing of the triggering receptor expressed on myeloid cells-2 (TREM2) by ectodomain shedding and γ-secretase dependent intramembranous cleavage"
Wunderlich, P., K. Glebov, N. Kemmerling, N. T. Tien, H. Neumann, J. Walter. J Biol. Chem. (2013)

 

Prof. Guy Brown

Prof. Guy Brown - University of Cambridge (UCAM)

 

 

Prof. Guy Brown is working at the University of Cambridge, UK

Visit his Lab-webpage or contact him

 

Work performed in PHAGO

“Our group is mainly looking at TREM2 and sTREM2 functions in work packages 2.2. and 2.3”

 

 Interesting readings and/or reviews about our work

1) "Reviews the evidence that neurodegeneration is due to endotoxin.”
"The endotoxin hypothesis of neurodegeneration"
Brown GC. J Neuroinflammation (2019)

 

2) "Paper showing that galectin-3 activates TREM2 and is required for amyloid pathology"
"Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer's disease"
Boza-Serrano A, Ruiz R, Sanchez-Varo R, García-Revilla J, Yang Y, Jimenez-Ferrer I, Paulus A, Wennström M, Vilalta A, Allendorf D, Davila JC, Stegmayr J, Jiménez S, Roca-Ceballos MA, Navarro-Garrido V, Swanberg M, Hsieh CL, Real LM, Englund E, Linse S, Leffler H, Nilsson UJ, Brown GC, Gutierrez A, Vitorica J, Venero JL, Deierborg T. Acta Neuropathol. (2019)

 

3) "Describes new method to knockdown gene expression in microglia, including TREM2 and CD33"
"Effective Knockdown of Gene Expression in Primary Microglia With siRNA and Magnetic Nanoparticles Without Cell Death or Inflammation. "
Carrillo-Jimenez A, Puigdellívol M, Vilalta A, Venero JL, Brown GC, StGeorge-Hyslop P, Burguillos MA. Front Cell Neurosci (2018)

 

4) "Reviews how neurons die, particularly in Alzheimer’s disease.”
"Neuronal Cell Death"
Fricker M, Tolkovsky AM, Borutaite V, Coleman M, Brown GC. Physiol Rev (2018)

 

5)"Reviews how microglial phagocytosis prunes neurons"
"Neurophagy, the phagocytosis of live neurons and synapses by glia, contributes to brain development and disease"
Vilalta A, Brown GC. FEBS J (2018)

 

Meet the Scientist -Oliver Cousins (KCL)

 

Dr Oliver Cousins
Clinical Research Fellow
Neurodegeneration Imaging Group
Maurice Wohl Clinical Neuroscience Institute
Institute of Psychiatry, Psychology & Neuroscience (IoPPN)
King’s College London

 


Can you explain your research within PHAGO in 2 sentences?

 I am aiming to explore the role of the immune system in Alzheimer’s disease by using a special type of brain scan, called a PET scan, to investigate the activation of brain immune cells (microglia) in people with and without memory problems, and in people with and without certain genes relating to the immune system (TREM2). I am also looking at the interactions of the immune cells with the abnormal proteins found in Alzheimer’s disease (Tau and Amyloid)

What do your friends and family think what you are doing in the lab?
I believe they think that I am performing brain scans on a daily basis

What are you really doing? (What’s your favourite task to do in the lab?)
Whilst I am occasionally preforming brain scans, the clinical assessments and participant recruitment takes a large proportion of my time. I enjoy the problem solving aspects of research, as I may be trying out a process that has not been performed before.

Why are you interested in Alzheimer’s Disease?
Alzheimer’s disease is a devastating condition that can ruin the lives of sufferers and their families (and I have had personal experience of such). Also, with the ageing population the costs to the health services will be crippling, particularly given the lack of therapies that can improve the clinical course of the disease.

What is the major challenge in Alzheimer research for you?
The disease processes are likely to start many years before symptom onset meaning that any future treatments are likely to need to take place early. However, being able to detect who may benefit, at this early stage, is especially challenging.

Trem2 or CD33?
Trem2 for me

Coffee or Tea?
Definitely tea. An important part of my British heritage.

Why does your research matter to the average citizen/man on the street?

We need to know how Alzheimer’s disease happens, otherwise any chance of a cure is very unlikely. Therefore, looking at a new angle to the disease, in our case the immune system, will help to solve the puzzle that are the processes underlying the disease.

The must-follow science twitter account?
I don’t use twitter…

The must-read article on Alzheimer research?
The original:- ‘TREM2 variants in Alzheimer's disease.’ (N Engl J Med. 2013 Jan 10;368(2):117-27.)

What else do you like to read (except research articles)?

I am working my way through the classics at the moment. I’ve just finished Lord of the Flies.

Your most surprising research finding?

This is my first real research project! Previously I was practicing clinical medicine, before taking this time out for research.

What is your personal highlight in PHAGO up to now?
I am working with a very rare group of people with very specific genes. The challenge of recruiting and building a relationship with such people (especially as the study has quite a few visits) has been a great experience for me.

What’s your favourite thing to do outside the lab?

I have a little baby boy and spending time with him, for example a recent trip to the seaside, is truly wonderful.

Best recent TV series/movie/novel depicting scientists?
A bit off the Alzheimer’s topic but I really enjoyed the film “the Martian.”  Good to see science in practice.

Meet the Scientist - Tamara Raschka (Fraunhofer)

Meet the Scientist - Tamara Raschka (Fraunhofer)

 

Tamara Raschka
PhD student
Fraunhofer Institute for Algorithms and Scientific Computing (SCAI)
Department of Bioinformatics Schloss Birlinghoven
Sankt Augustin, Germany

 


Can you explain your research within PHAGO in 2 sentences?

As a bioinformatician, I am analyzing the transcriptomic (gene expression) data coming up in the project e.g. to see the effect of knock-out experiments of CD33 and TREM2. This will allow the validation of the hypothetical pathways those two genes are involved in.

What do your friends and family think what you are doing in the lab?
They think I am working in a lab, but actually, as a bioinformatician, I am just sitting in front of my computer, not doing anything in a lab :D

What are you really doing? (What’s your favourite task to do in the lab?)
My favourite task while analyzing the data is to find a good and interesting way to analyze it and to solve the appearing problems with innovative ideas.

Why are you interested in Alzheimer’s Disease?
Alzheimer’s Disease is a disease that influences the people a lot, but still, it’s not clear what causes it and how it can be treated. That makes Alzheimer’s Disease one of the most interesting research areas where many things still need to be examined.

What is the major challenge in Alzheimer research for you?
A major challenge is the fact, that people are just diagnosed after being affected by the disease already many years. That is why we are missing the disease onset in many cases and can just look into the later stages of the disease.

Trem2 or CD33?
CD33

Coffee or Tea?
Coffee

Why does your research matter to the average citizen/man on the street?

Because everyone gets older ;-) And we need to find the causes and mechanisms of Alzheimer’s to be able to treat it in an effective way to make the patient’s life better.

The must-follow science twitter account?
I am not on Twitter...

The must-read article on Alzheimer research?

Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease" (Cell. 2013 Apr 25;153(3):707-20)


What else do you like to read (except research articles)?

Exciting thrillers

Your most surprising research finding?
That my frustration tolerance increases more and more while doing research ;-)

What is your personal highlight in PHAGO up to now?
As a highlight, I would definitely state the connections to the other scientists of the project. There is a wide range of different scientists that makes meeting and working closely together with them  pleasant and fruitful.

What’s your favourite thing to do outside the lab?
Being in nature: Hiking, biking or even climbing

Best recent TV series/movie/novel depicting scientists?
„Helix“ written by Marc Elsberg

Meet the Scientist - Mara Tornincasa (Axxam)

Meet the Scientist - Mara Tornincasa (Axxam)

 

Mara Tornincasa, Ph.D.
Scientist, Compound Profiling Unit
Hit Tailoring Solutions
Axxam SpA
Openzone – Via Meucci 3
Bresso, Italy

 


Can you explain your research within PHAGO in 2 sentences?

My research for Phago is focalized on drug discovery program to test and identify small molecules active on target TREM2. My goal is to understand if they could act on TREM2 as agonists or positive allosteric modulators.

What do your friends and family think what you are doing in the lab?
My friends think that my job is very rewarding while my family thinks I'm always stressed.

What are you really doing? (What’s your favourite task to do in the lab?)
I’m working on an innovative project. Actually, my favourite task is to optimize new protocols to improve the performance of compounds testing. The aim is to identify the best molecules based on the structure and the activity of compounds.

Why are you interested in Alzheimer’s Disease?
My interest is strong for neurodegenerative disease as Alzheimer based on my previous experience in neurodegenerative field and for my scientific training.

What is the major challenge in Alzheimer research for you?
Specific challenges faced by those with younger-onset Alzheimer's.

Trem2 or CD33?
Trem2

Coffee or Tea?
Coffee

Why does your research matter to the average citizen/man on the street?

Alzheimer is a neurodegenerative disorder with a strong impact on the society and there are some cases with early onset.

The must-follow science twitter account?
I don’t have a twitter account

The must-read article on Alzheimer research?

"TREM2 in Alzheimer’s Disease: Microglial Survival and Energy Metabolism.”  (Front Aging Neurosci. 2018 Nov 23;10:395)


What else do you like to read (except research articles)?

I like to read novels and comedies.

Your most surprising research finding?
My most surprising research was the identification of a gene involved in neurodegeneration, in particular in cerebellar ataxia.

What is your personal highlight in PHAGO up to now?
Identification of a specific TREM2 agonist by screening of Prestwick library.

What’s your favourite thing to do outside the lab?
I like to hear music, go to concert and go to gym.

Best recent TV series/movie/novel depicting scientists?
It’s not recent TV series...Grey’s Anatomy.

Meet the Scientist - Mona Mathews (Life & Brain)

Meet the Scientist - Mona Mathews (Life & Brain)

 

Mona Mathews, Dr.rer.nat.
Scientist

LIFE & BRAIN GmbH
Cellomics Unit
Venusberg-Campus 1
Bonn, Germany

 


Can you explain your research within PHAGO in 2 sentences?

I am involved in optimizing and validating stem-cell-derived models of immune cells from patients with dementia. I believe that a robust and reliable model system is critical to obtain dependable data for studying dementia.

What do your friends and family think what you are doing in the lab?
My family always ask if my work is like they see on TV shows such as Dr. House or Bones! My friends (most of whom have also studied STEM) have a better idea of what I am doing, but they often ask about the ethical standpoints of stem cell research. We’ve had some passionate conversations about society, science and ethics.

What are you really doing? (What’s your favourite task to do in the lab?)
My favourite thing to do in the lab is to invent new methods or techniques that help optimize my standard protocols. I love using knowledge and material from other sciences such as Bioengineering, Chemistry to improve my own Biological research techniques.


Why are you interested in Alzheimer’s Disease?
I find the complexity of dementia in general, and Alzheimer’s in particular, extremely intriguing! While I am more involved in basic research and not clinical research, I still hope that any information I can contribute towards this field will be useful in benefiting those affected by this disease.


What is the major challenge in Alzheimer research for you?
There is a huge community of scientists that continuously generate some pretty amazing data that help us understand the disease better every day! Honestly, I find it overwhelming to keep up with this influx of information and that’s why I am very excited about new initiatives from different groups to co-ordinate and stream-line the data generated (for example Neuronet from Innovative medicines initiative).


Trem2 or CD33?
CD33! I spent my entire PhD thesis on studying CD33 and its pathway. I think it’s safe to say that I will always have a preference to hear about the new data generated on CD33 – out of habit but also scientific passion!


Coffee or Tea?
Tea! Especially some delicious peppermint tea always helps calm me down on a stressful day.

Why does your research matter to the average citizen/man on the street?
Every bit of data helps complete the entire story of understanding how to deal with and hopefully, eventually how to prevent or cure specific diseases.

The must-follow science twitter account?
@sciencegoddess and @Jule_Fischer_BN

Inspiring women scientists!

The must-read article on Alzheimer research?
https://www.cell.com/cell/fulltext/S0092-8674(15)00127-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867415001270%3Fshowall%3DtruePersonally, I love the paper from the group of Knut Biber published in Scientific reports in 2015 about the development of plaques in an animal model. This is because reading that paper gave me an idea for my PhD thesis project that I am quite proud of!
"Forebrain microglia from wild-type but not adult 5xFAD mice prevent amyloid-β plaque formation in organotypic hippocampal slice cultures."
(Sci Rep. 2015 Sep 29;5:14624)


What else do you like to read (except research articles)?

Autobiographies/Biographies of famous politicians and famous scientists 
And my go-to-book that I find myself re-reading every few years is “The life of Pi” by Yann Martel.

Your most surprising research finding?
In my experience, I am always surprised to see how much we can learn from simplistic models in the lab. In a previous research project, I looked at the ability of human cells to express non-human sugars and was pleasantly surprised to find that my most simple treatment worked the best, while my more complicated treatments gave me confusing and complicated results.

What is your personal highlight in PHAGO up to now?
The transparency and cooperation. My colleagues in other research groups have also commented (sometimes enviously!) on the good interaction of the partners within PHAGO.

What’s your favourite thing to do outside the lab?
Travelling! My husband and I are on a quest to visit all the new 7 wonders of the world. So far, I have seen 3 and my husband has seen 4. We will soon be on our way to the next one, the tickets are booked for Petra, Jordan!

Best recent TV series/movie/novel depicting scientists?
Well the following series is not about scientists but about nature. Although I am not answering this question accurately, I can’t stop myself from recommending Planet Earth narrated by Sir David Attenborough. I’m currently on the second part of the series and find it absolutely amazing!

Meet the Scientist - Paola Picardi (Axxam)

Meet the Scientist - Paola Picardi (Axxam)

 

Paola Picardi, Ph.D.
Scientist, Cell Biology

Axxam SpA
Openzone – Via Meucci 3
Bresso, Italy

 


Can you explain your research within PHAGO in 2 sentences?

Development of cell-based assay for TREM2 and CD33, suitable for High Throughput Screening (HTS) purpose and the adaptation to HTS platform of cell-based assay generated by partners.

What do your friends and family think what you are doing in the lab?
My friends think that I have fun with the cells (not well identified material). My family thinks I am stressed by the cells (not well identified material).

What are you really doing? (What’s your favourite task to do in the lab?)
I generated an innovative cell-based assay to validate TREM2 agonists and I tested all the quality criteria required by industry-standards (robustness, reproducibility, signal stability). Therefore, the assay is suitable for compound testing in industrial settings, aimed to the identification of pharmacological tool compounds for the treatment of Alzheimer Disease.

Why are you interested in Alzheimer’s Disease?
AD is a growing epidemic across the globe and the identification of suitable therapeutic approaches represents one of the greatest medical challenges.

What is the major challenge in Alzheimer research for you?
The identification of effective treatments having into account the multifactorial nature of the disease.

Trem2 or CD33?
Trem2

Coffee or Tea?
Coffee

Why does your research matter to the average citizen/man on the street?

AD is the most common dementia in the elderly and the world’s population is ageing.

The must-follow science twitter account?
I do not use twitter.

The must-read article on Alzheimer research?

"TREM2 lipid sensing sustains microglia response in an Alzheimer’s disease model”  (Cell. 2015 Mar 12;160(6):1061-71.)


What else do you like to read (except research articles)?

Novels

Your most surprising research finding?
The genetic and pharmacological inactivation of cannabinoid CB1 receptor is able to inhibit angiogenesis.

What is your personal highlight in PHAGO up to now?
The generation of a robust assay for TREM2 activation already used to run a screening activity that identified a specific TREM2 agonist.

What’s your favourite thing to do outside the lab?
To go to the theatre.

Best recent TV series/movie/novel depicting scientists?
Dr House

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This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115976. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA companies.

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This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115976. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA companies.