Multiple sclerosis (MS) is a prototypic and progressive neuroimmune disease with several clinical phenotypes and is usually associated with progressive cognitive and physical disabilities and shortened life span. Infiltration of the central nervous system (CNS) by innate- and adaptive immune cells, neuroinflammation within the CNS, disruption of the blood-brain barrier (BBB), and also demyelination and axonal disruption are characteristics of MS. Bacteria, viruses, environmental factors or a certain genetic background may contribute to MS manifestation. Yet, a definitive causative is not defined.
Along with my research background, my research interest focuses on pathogen induced inflammatory processes (in particular on the Treg-Th17 axis) in the peripheral system, and potentially resulting tissue disruption/demyelination and cell death of neurons and oligodendrocytes in the CNS. The understanding of T-cell (Th1 and Th17) mediated inflammatory processes that are eventually driven by an external trigger (e.g. a virus) may provide crucial information as to how disease initiates and progresses but may also help to identify therapeutic targets and strategies.

My previous work focused on the complex interaction network between viruses and their hosts. Understanding of such networks enables development of antiviral strategies that help to mitigate or cure diseases that otherwise may have severe consequences. I conducted pioneering work on diverse virus systems and established an array of new techniques including cell culture-, biochemical- and microscopy-based assays to analyze the virus replication cycle and virus-host interactions. This included ELISA, BioPlex, RT-qPCR, SDS-PAGE, Western Blot, BiaCore, HPLC, LC-MS, FACS, HTS- and confocal microscopy.

While exploring essential viral genes needed for nuclear egress of mouse and human cytomegalovirus (MCMV/ HCMV) I gained experience working with DNA viruses. Next, I ventured into the RNA-virus world and became interested in the infection biology of human rhinoviruses (HRVs). These viruses are the major cause of common cold, but they also seem to be associated with asthma and COPD (Chronic Obstructive Pulmonary Disease). Upon infection, both DNA and RNA viruses are detected by cells of the innate immune system leading to cytokine release, inflammation and subsequently virus clearing. However, viruses developed multiple strategies to escape detection by the immune system, to modulate immune response and to manipulate cell death in order to guarantee virus progeny.

Such immune evasion mechanisms can alter disease manifestation and could be deleterious under certain genetic background conditions, too. Thus, besides assay development and hit validation of large genome-wide screens (HTS), my major focus was the analysis of rhinovirus-induced cell death pathways and immune evasion mechanisms. I could show that HRVs target certain key proteins of apoptotic and necrotic cell death regulation and -execution to guarantee progeny and to establish their own mode of inflammatory death.

Mark Lötzerich, Pascal S. Roulin, Karin Boucke, Robert Witte, Oleg Georgiev and Urs F. Greber.

Rhinovirus 3C protease suppresses apoptosis and triggers caspase independent cell death. Cell Death Dis., 2018, 9(3):272

 

Pascal Roulin, Mark Lötzerich, Andreas Jurgeit, Stefan Moese and Urs F. Greber.

The oxysterol-binding protein mediates cholesterol recruitment via phosphatidylinositol 4-kinase III-beta activity to enhance human rhinovirus replication. Cell Host Microbe. 2014 Nov 12; 16(5):677-90; PMID: 25525797

 

Jurgeit A., Moese S., Roulin P., Dorsch A., Lötzerich M., Lee WM and U. F. Greber.

An RNA replication-center assay for high content image-based quantifications of human rhinovirus and coxsackievirus infections.

Virol J. 2010 Oct 11; 7:264; PMID: 20937137

 

Mirela Popa, Zsolt Ruzsics, Mark Lötzerich, Lars Dölken, Christopher Buser, Paul Walther, and Ulrich H. Koszinowski.

Dominant Negative Mutants of the Murine Cytomegalovirus M53 Gene Block Nuclear Egress and Inhibit Capsid Maturation.

J Virol. 2010 Sep; 84(18):9035-46; PMID: 0610730

 

Mark Lötzerich, Zolt Ruzsics and Ulrich H. Koszinowski.

Functional domains of murine cytomegalovirus nuclear egress protein M53/p38.

J Virol. 2006 Jan; 80(1):73-84; PMID: 16352532

 

Anja Bubeck, Markus Wagner, Zsolt Ruzsics, Mark Lötzerich, Margot Iglesias, R. Singh, and Ulrich H. Koszinowski.

Comprehensive mutational analysis of a herpesvirus gene in the viral genome context reveals a region essential for virus replication.

J Virol. 2004 Aug; 78(15):8026-35; PMID: 15254174

 

Löms Ziegler-Heitbrock, Mark Lötzerich, Annette Schaefer, Thomas Werner, Marion Frankenberger, and Elke Benkhart.

IFN-a induces the human IL-10 gene by recruiting both IFN regulatory factor 1 and Stat3.

J Immunol. 2003 Jul 1; 171(1):285-90; PMID: 12817009