Project Coordinator
Prof. Dr. Hans-Ulrich Demuth

Head of Department for Drug Design and Target Validation
Fraunhofer Institute for Cell Therapy and Immunology IZI
Weinbergweg 22
06120 Halle (Saale)
Germany
hans-ulrich.demuth@izi.fraunhofer.de

Professor Demuth is a leading expert in deciphering the biochemical basis of pathophysiological conditions such as metabolic and neurodegenerative disorders. Formally trained as biochemist at the University of Halle, Germany, his academic career took him to the US and Sweden, while currently holding a Professorship of Pharmabiotechnology at the Anhalt University of Applied Sciences. As the co-founder of probiodrug AG, he held responsible for research and development of dipeptidyl peptidase 4 (DPIV) and glutaminyl cyclase inhibitors. To further focus on the mechanisms of neurodegenerative diseases, he now heads the Department of Drug Design and Target Validation [LINK] of the Fraunhofer Insitute for Cell Therapy and Immunology [LINK] and a team of 30 researchers. Demuth’s general research focuses on bioorganic mechanisms, enzyme-inhibitor interactions and the development of potential drugs to treat Metabolic Disorders, CNS Disorders and Immune Disorders employing assay development, pre-clinical studies, biochemistry, molecular biology, etymology and organic chemistry. He authored and co-authored more than 120 issued and published patents.

For CrossSeeds, Professor Demuth and his team will focus on studying the co-aggregation of amyloid peptides in vitro. Furthermore, it is an aim to generate antibodies directed against the amyloid species and to provide active vaccine for treatment studies at the partner institutions.

Selected publications

S. Schilling, ..., H.U. Demuth, S. Roßner (2008) Glutaminyl cyclase inhibition attenuates pyroglutamate Abeta and Alzheimer's disease-like pathology. Nat. Med. 14, 1106-1111.

H. Cynis, ..., H.U. Demuth (2011) The isoenzyme of glutaminyl cyclase is an important regulator of monocyte infiltration under inflammatory conditions. EMBO Mol. Med. 3, 545-558.

B. Koch, ..., H.U. Demuth (2012) Probing secondary glutaminyl cyclase (QC) inhibitor interactions applying an in silicomodeling/ site-directed mutagenesis approach: implications for drug development. Chem. Biol. Drug Des. 80, 937-46.

J. Nussbaum, ..., H.U. Demuth*, G.S. Bloom* (2012) Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-ß Nature 485, 651-655 (* corresponding authors)

J. Frost, ..., H.U. Demuth, C.A. Lemere (2013) Pyroglutamate-3 amyloid-ß deposition in the brains of humans, non-human primates, canines, and Alzheimer disease-like transgenic mouse models. Am. J. Patho/. 183, 369-81.

 


Prof. Dr. Steffen Roßner

University of Leipzig, Germany
Paul-Flechsig-Institute for Brain Research
Liebigstrasse 19
04103 Leipzig, Germany

Professor Steffen Roßner is Associate Professor at the University of Leipzig’s Paul-Flechsig-Institute for Brain Research. Trained as a biochemist, he received his PhD in biochemistry in 1995, then joining the University of Leipzig and working as a post-Doc at the University of Texas Medical Branch at Galveston. His research focuses on molecular and cellular mechanisms of protein aggregation in Alzheimer’s Disease and related disorders, neuroinflammation and gliosis in age-related brain disorders as well as the development of novel cell cultures and animal models to study neurodegenerative diseases.

Prof. Roßner and his team are dedicated to analyze the co-aggregation of A-beta in transgenic mouse and rat models. Furthermore, the group will characterize the cytotoxicity of amyloid co-aggregates and will evaluate the efficacy of vaccines in AD rodent models.

Selected publications

M. Morawski, M., ..., H.U. Demuth, S. Roßner (2010) Distinct glutaminyl cyclase expression in Edinger-Westphal nucleus, locus coeruleus and Ncl. basalis Meynert contributes to pGlu-Aß pathology in Alzheimer's disease. Acta Neuropathol. 120, 195-207.

P. H. Kuhn, ..., S. Roßner, S. F. Lichtenthaler (2010) ADAM 10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons. EMBO J. 29, 3020-3032.

M. Hartlage-Rübsamen, ..., H.U. Demuth, S. Roßner (2011) Glutaminyl cyclase contributes to the formation of focal and diffuse pyroglutamate (pGlu)-Aß deposits in hippocampus via distinct cellular mechanisms. Acta Neuropathol. 121, 705-719.

M. Morawski, S. Schilling, M. Kreuzberger, A. Waniek, C. Jäger, B. Koch, H. Cynis, A. Kehlen, T. Arendt, M. Hartlage-Rübsamen, H.U. Demuth, S. Roßner (2014) Glutaminyl cyclases in human cortex – Correlation with (pGlu)-Abeta load and cognitive decline in Alzheimer’s disease. J. Alzh. Dis. 39, 385-400.

M. Hartlage-Rübsamen, A. Waniek, J. Meißner, M. Morawski, S. Schilling, C. Jäger, M. Kleinschmidt, H. Cynis, A. Kehlen, T. Arendt, H.U. Demuth, S. Roßner (2015) Isoglutaminyl cyclase contributes to CCL2-driven neuroinflammation in Alzheimer’s disease. Acta Neuropathol. 129, 565-583.

 


Dr. Stéphane Hunot

Brain & Spine Institute (ICM)
Pierre et Marie Curie University – Inserm
ICM-Inserm/UPMC UMRS 1127 – CNRS UMR 7725
Paris, France

Stéphane Hunot is Research Director at CNRS. Following receipt of his PhD in cell biology and physiology in 1998 (Pierre et Marie Curie University, Paris), he joined the Section of Immunology at Yale School of Medicine (New Haven, CT) in the laboratory of Pr. Richard Flavell as a post-doctoral fellow where he was trained in molecular biology studying molecular pathways of cell death. It was during this period, being in contact with outstanding immunologists, that he fully realized how much interesting and important the interactions between the immune and nervous systems could be, especially in neurodegenerative conditions. In 2001, he joined the team of Dr Etienne Hirsch at the Salpêtrière Hospital (INSERM, Paris) and established a new research program focused on neuro-immune interactions in Parkinson's disease. Stéphane Hunot is a member of several professional societies and serves on the scientific advisory board for the Association France Parkinson (2006-2012) and the Fondation de France (since 2013). He is a referee for numerous international journals and National agencies.

The research group of Dr. Hunot will study the co-aggregation of alpha-synuclein and other amyloid peptides (A-beta, huntingtin) in transgenic mice. Moreover, the rodent models will undergo extensive phenotypical characterization. A further aim is to analyze the efficacy of active immunization on the pathology.

Selected publications

V. Brochard, ..., E.C. Hirsch, S. Hunot (2009) Brain infiltration of CD4 lymphocytes contributes to neurodegeneration in Parkinson's disease model. J. Clin. lnvest. 119, 182-192.

F. Ros Bemal*, S. Hunot*, ..., S. Vyas (2011) Microglial glucocorticoid receptors play a pivotal role in regulating dopaminergic neurodegeneration in Parkinsonism. Proe. Natl. Aead. Sei. USA 108, 6632-6637. *co-first authors

E. Rousselet, ..., S. Hunot (2012) Tumor necrosis factor-like weak inducer of apoptosis induces astrocyte proliferation through the activation of transforming-growth factor-a/epidermal growth factor receptor signaling pathway. Mol. Pharmaeol. 82, 948-957.

K. Kinugawa, ..., S. Hunot (2013) MFGE8 does not orchestrate clearance of apoptotic neurons in a mouse model of Parkinson's disease. Neurobiol. Dis. 51, 192-201.

C. Noelker, ..., S. Hunot *, A. Hartmann* (2014) Toll like receptor 4 mediates cell death in a mouse MPTP model of Parkinson disease. Sei Rep. 3, 1393. *eo-senior authors

 


Prof. Dr. Stephan von Hörsten

Friedrich-Alexander-University Erlangen-Nürnberg, Germany
Universitätsklinikum
Department of Experimental Therapy
Palmsanlage 5
91054 Erlangen
Germany

Prof. Dr. Stephan von Hörsten graduated from Medical School Hannover in 1994, holding various positions at this institution until his appointment as Professor for Experimental Biomedicine at the Friedrich-Alexander-University in Erlangen (FAU) in 2006. Since 2007, he took office as scientific director of the Preclinical Experimental Research Center (PETZ) at FAU and is now managing director of PETZ and Head of Department for Experimental Therapy at FAU. His research spans neurodegenerative disorders focusing on Huntington’s and Alzheimers diseases. His expertise lies in perinatal programming of disease susceptibility with focus on inflammatory and brain disorders, neuro-immune-endocrine interactions as well as comprehensive phenotyping of rodent models for human disorders. He employs a wide array of methods from biochemistry, molecular biology, histology, stereology and comprehensive phenotyping of mice and rats.

Prof. von Hörsten and his team will focus on analysis of amyloid species in rodent animal models of HD. Part of his work will be a phenotypical characterization of HD mice, co-aggregation of huntingtin with A-beta and alpha-synuclein and evaluation of a potential treatment.

Selected publications

S. von Hörsten, ..., O. Riess (2003) Transgenic rat model cf Huntington's disease. Hum. Mol. Genet. 12, 617-624.

H.P. Nguyen, ..., S. von Hörsten (2006) Behavioral abnormalities precede polyglutamine recruitment and aggregates in rats transgenic for Huntington's Disease. Hum. Mol. Genet. 15, 3177-3194.

U. Forssmann, ..., S. von Hörsten (2008) Inhibition cf CD26/dipeptidyl peptidase 4 enhances CCL 11/eotaxin-mediated recruitment of eosinophils in vive. J. lmmunol. 181, 1120-1127.

C. Kruschinski, ..., S. von Hörsten (2008) Postnatal life events affect the severity cf asthmatic airway inflammation in the adult rat. J. lmmunol. 180, 3919-3925.

A. Alexandru, ..., H.U. Demuth, S. von Hörsten (2011) Selective hippocampal neurodegeneration in transgenic mice expressing small amounts of truncated Aß is induced by Pyro-Glu-Aß formation. J. Neurosci. 31, 12790-12801.

 


Prof. Dr. Jan G. Bjaalie

University of Oslo, Norway
Institute of Basic Medical Sciences
Domus Medica
Gaustad Sognsvannsveien 9
0372 Oslo

Prof. Dr. Bjaalie received his Ph.D. in neuroanatomy from the University of Oslo in 1990. He was Executive Director at the International Neuroinformatics Coordinating Facility, Karolinska institutet, Stockholm and is now Head of the Institute of Basic Medical Sciences, University of Oslo. His academic interest focuses on neuroinformatics from ontologies to cyberinfrastructure for data management and sharing as well as brain architecture and digital brain atlasing, wiring patterns of the brain / brain connectivity and map transformations in sensory systems of the brain. Professor Bjaalie is highly engaged in academia as editor and member of various editorial boards of several journals. He currently serves as the Norwegian representative of the Governing Board of the International Neuroinformatics Coordinating Facility.

Professor Bjaalie and his team will intensively interact with the other research groups to generate a brain-wide map of the distribution of peptides acting as seeds for protein aggregation. Specifically, the following research questions will be addressed: (i) image processing to extract intensity and distribution of labelling for the pathogenic proteins, (ii) registration to digital brain atlases, with assignment of protein distribution to brain regions and (iii) brain-wide visualization of densities and distribution of the pathogenic proteins.

Selected publications

l.A. Moene, S. Subramaniam, ..., T,B. Leergaard, J.G. Bjaalie (2007) Toward a workbench for rodent brain image data: systems architecture and design. Neuroinformatics 5, 35-58.

F. Odeh, T.B. Leergaard, ..., O. Riess, J.G. Bjaalie (2011) Atlas of transgenic Tet-Off Ca2+/calmodulin-dependent protein kinase II and prion protein promoter activity in the mause brain. Neuroimage 54, 2603-2611.

I.M. Zakiewicz, Y.C. van Dangen, T.B. Leergaard, J.G. Bjaalie (2011) Workflow and atlas system for brain-wide mapping of axonal connectivity in rat. PLoS One 6, e22669.

S. Lillehaug, ..., J.G. Bjaalie, T.B. Leergaard, R. Torp (2014) Brainwide distribution and variance of amyloid-beta deposits in tgArcSwemice. Neurobiol. Aging 35, 556-564.

E. Papp, T.B. Leergaard, ..., G.A. Johnson, J.G. Bjaalie (2014) Waxholm Space atlas of the Sprague Dawley rat brain. Neuroimage 97, 374-386.

Funding

JPND logo BMBF logo

The EU Joint Programme – Neurodegenerative Disease Research (JPND) is the largest global research initiative aimed at tackling the challenge of neurodegenerative diseases. JPND aims to increase coordinated investment between participating countries in research aimed at finding causes, developing cures, and identifying appropriate ways to care for those with neurodegenerative diseases – www.jpnd.eu