Chromatin and SUMO physiology group

Research focus

Mobility is an indispensable feature that determines survival and success in the animal world. Skeletal muscle- that allows this mobility- is an astounding organ constituting over 650 muscles accounting for approximately 40% of total body mass and up to 30% of basal energy expenditure. The skeletal muscle displaying a characteristic striated pattern is an array of linearly arranged units called ‘sarcomeres’. The individual sarcomere hosts highly organized structures including the actin, and myosin filaments. The cyclic interaction between these two types of filaments is responsible for generation of force and movement at the molecular to organismic level.

Precise molecular arrangement of sarcomere is central to the muscle function. Importantly, disorganization of sarcomere and thereby defective muscle function are the typical hallmarks of myopathies including cancer cachexia, prevalent in nearly 80% of cancer patients with reported mortality rate in more than 30% patients.

The major focus of our group is understand how SUMO (Small Ubiquitin-like Modifier)-mediated epigenetic program regulates skeletal and cardiac muscle physiology including sarcomere organization, muscle differentiation and regeneration process and muscle wasting diseases such as cachexia. Other major aim of our group is to understand the molecular mechanism of chemotherapy-induced cachexia. Our ongoing projects has established unbiased screening systems to test effects of various chemotherapeutic drugs on muscle wasting with an objective to identify a better therapeutic option that will reduce cancer burden without triggering loss of muscle mass and function.

Lab Projects

• ​Modulation of chromatin organization by SUMO pathway in myofibril assembly
• Epigenetic signaling in muscle atrophic condition/Cachexia
• Mechanism underlying chemotherapy-induced cachexia
• SUMOs in cachexia and muscle cell metabolism

Lab Members

Principal Investigator: Arnab Nayak

PhD student: Luis Gand

PhD student: Bushra Khan

PhD student: Mugeng Li

PhD student: Prasanth Pillai

PhD student: Baoyu Zhou

technical assistant: Stefanie Nedel (Medizinischen Technologinnen für Laboratoriumsanalytik)

With her excellent technical expertise in cell and molecular biology Stefanie is involved in various projects of the group.

Lab Methodologies

To address our scientific objectives, we employ diverse experimental approaches, including quantitative proteomics, SUMO proteomics, CRISPR/Cas9-mediated genome editing tools to check chromatin events of a single gene, epigenomics (ChIPseq, chromosome conformation capture etc.), cell contractility assay, measurement and quantification of calcium transient process and single molecule biophysical methods such as total internal reflection fluorescence microscopy (TIRFM).

Funding

• Individual research grant from the German Research foundation (DFG). NA 1565/2-1, . €235,750
• Individual research grant from the German Cancer Aid (DKH). Identification no.- 70115510. 303.900 €.  

Selected publications

• Bushra Khan, Luis Vincens Gand, Mamta Amrute-Nayak, Arnab Nayak, Emerging Mechanisms of Skeletal Muscle Homeostasis and Cachexia: The SUMO Perspective, Cells, 2023 Feb 17;12(4):644, doi: 10.3390/cells12040644, PubMed
   
• Identification of galectin-3 as a novel potential prognostic/predictive biomarker and therapeutic target for cerebral cavernous malformation disease, Souvik Kar, Andrea Perrelli, Kiran Kumar Bali, Raffaella Mastrocola Arpita Kar, Bushra Khan, Luis Gand, Arnab Nayak, Christian Hartmann, Wolfram S. Kunz, Amir Samii, Helmut Bertalanffy, Saverio
  Francesco Retta, Genes & Diseases, Available online 3 April 2023 ScienceDirect, doi.org/10.1016/j.gendis.2023.02.045
   
• Mamta Amrute-Nayak, Luis Vincens Gand, Bushra Khan, Tim Holler, Ekaterini Kefalakes, Maike Kosanke, Theresia Kraft, and Arnab Nayak, SENP7 deSUMOylase-governed transcriptional program coordinates sarcomere assembly and is targeted in muscle atrophy, , 2022, Cell Reports 41, 111702, https://doi.org/10.1016/j.celrep.2022.111702
   
• Mamta Amrute-Nayak, Gloria Pegoli, Tim Holler, Alfredo Jesus Lopez-Davila, Chiara Lanzuolo, Arnab Nayak,Chemotherapy triggers cachexia by deregulating synergetic function of histone-modifying enzymes, J Cachexia Sarcopenia Muscle, 2020 Dec 10., doi: 10.1002/jcsm.12645. Online ahead of print, PubMed
   
• Wang T, Brenner B, Nayak A, and Amrute-Nayak M, Acto-Myosin Cross-Bridge Stiffness Depends on the Nucleotide State of Myosin II, Nano Letters, 2020 Sep 15. doi: 10.1021/acs.nanolett.0c02960. [Online ahead of print] PubMed
   
• Nayak A*, Lopez-Davila AJ, Kefalakes E, Holler T, Kraft T, Amrute-Nayak M. (2019). Regulation of SETD7 Methyltransferase by SENP3 is Crucial for Sarcomere Organization and Cachexia. Cell Reports. Vol 27, issue 9, P2725-2736.e4, May 28. (*corresponding author)

• Amrute-Nayak M, Nayak A, Steffen W, Tsiavaliaris G, Scholz T, Brenner B. (2019). Transformation of Conventional, Non-processive Myosin II into a Fast Processive Motor. (2019). Small. Feb;15(7)

• Nayak, A*., Reck, A., Morsczeck, C., and Muller, S. (2017). Flightless-I governs cell fate by recruiting the SUMO isopeptidase SENP3 to distinct HOX genes. Epigenetics Chromatin .10, 15. (* corresponding author)

• Jung, J., Nayak, A., Schaeffer, V., Starzetz, T., Kirsch, A.K., Muller, S., Dikic, I., Mittelbronn, M., and Behrends, C. (2017). Multiplex image-based autophagy RNAi screening identifies SMCR8 as ULK1 kinase activity and gene expression regulator. Elife 6

• Nayak, A., Viale-Bouroncle, S., Morsczeck, C., and Muller, S. (2014). The SUMO-specific isopeptidase SENP3 regulates MLL1/MLL2 methyltransferase complexes and controls osteogenic differentiation. Mol Cell 55, 47-58

• Nayak, A., Glockner-Pagel, J., Vaeth, M., Schumann, J.E., Buttmann, M., Bopp, T., Schmitt, E., Serfling, E., and Berberich-Siebelt, F. (2009). Sumoylation of the transcription factor NFATc1 leads to its subnuclear relocalization and interleukin-2 repression by histone deacetylase. J Biol Chem 284, 10935-10946.
   
• Nayak, A., and Muller, S. (2014). SUMO-specific proteases/isopeptidases: SENPs and beyond. Genome Biol 15, 422.

Collaboration

• Dr. Chiara Luanzolo

• Institute of Biomedical Technologies (ITB)-CNR
  Chromatin and Nuclear architecture Laboratory
  at Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi”  Milan, Italy
   
• Prof. Dr. med. Susanne Petri
  Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany

• Prof. Riikka Kivela
  Stem Cells and Metabolism Research Program, Faculty of Medicine. University of Helsinki, Finland. Faculty of Sport and Health Sciences. University of Jyväskylä, Finland

• Prof. Dr. med. Michael Heuser
  Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School.
   

Teaching

• Practical courses for medical students (Human medicine and dentists)
• Seminars for medical students
• Practical courses for biology students
• Practical courses for MSc “Biomedicine” students
• Ph.D. theses in Biology and Medicine