AG Nayak
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: Katharina Brandt
PhD student: Luis Gand
PhD student: Amel Nassar-Grioua
PhD student: Mugeng Li
PhD student: Baoyu Zhou
Technical assistant: Stefanie Nedel
Previous lab members
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Bushra Khan PhD.
Funding
- Individual research grant from the German Research foundation (DFG). NA 1565/2-1
- Individual research grant from the German Cancer Aid (DKH). Identification no.- 70115510.
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).
Selected publications (*corresponding author)
- Gand LV, Lanzuolo C, Li M, Rosti V, Weber N, Lu D, Bar C, Thum T, Pich A, Kraft T, Amrute-Nayak M, Nayak A* (2025) Calcium Handling Machinery and Sarcomere Assembly are Impaired Through Multipronged Mechanisms in Cancer Cytokine-Induced Cachexia. J Cachexia Sarcopenia Muscle 16: e13776
- Khan B, Lanzuolo C, Rosti V, Santarelli P, Pich A, Kraft T, Amrute-Nayak M, Nayak A* (2024) Sorafenib induces cachexia by impeding transcriptional signaling of the SET1/MLL complex on muscle-specific genes. iScience 27: 110913
- Wang T, Nayak A, Kraft T, Amrute-Nayak M (2024) Single-Molecule Investigation of Load-Dependent Actomyosin Dissociation Kinetics for Cardiac and Slow Skeletal Myosin. Small 20: e2406865
- Spahiu E, Uta P, Kraft T, Nayak A*, Amrute-Nayak M (2024) Influence of native thin filament type on the regulation of atrial and ventricular myosin motor activity. J Biol Chem 300: 107854
- Khan B, Gand LV, Amrute-Nayak M, Nayak A* (2023) Emerging Mechanisms of Skeletal Muscle Homeostasis and Cachexia: The SUMO Perspective. Cells 12
- Amrute-Nayak M, Gand LV, Khan B, Holler T, Kefalakes E, Kosanke M, Kraft T, Nayak A* (2022) SENP7 deSUMOylase-governed transcriptional program coordinates sarcomere assembly and is targeted in muscle atrophy. Cell Rep 41: 111702
- Wang T, Spahiu E, Osten J, Behrens F, Grunhagen F, Scholz T, Kraft T, Nayak A*, Amrute-Nayak M (2022) Cardiac ventricular myosin and slow skeletal myosin exhibit dissimilar chemomechanical properties despite bearing the same myosin heavy chain isoform. J Biol Chem 298: 102070
- Wang T, Brenner B, Nayak A*, Amrute-Nayak M (2020) Acto-Myosin Cross-Bridge Stiffness Depends on the Nucleotide State of Myosin II. Nano Lett 20: 7506-7512
- Amrute-Nayak M, Pegoli G, Holler T, Lopez-Davila AJ, Lanzuolo C, Nayak A* (2020) Chemotherapy triggers cachexia by deregulating synergetic function of histone-modifying enzymes. J Cachexia Sarcopenia Muscle
- Nayak A*, Amrute-Nayak M (2020) SUMO system - a key regulator in sarcomere organization. FEBS J 287: 2176-2190
- Nayak A, Wang T, Franz P, Steffen W, Chizhov I, Tsiavaliaris G, Amrute-Nayak M (2020) Single-molecule analysis reveals that regulatory light chains fine-tune skeletal myosin II function. J Biol Chem 295: 7046-7059
- 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 Rep 27: 2725-2736 e4
- Amrute-Nayak M, Nayak A, Steffen W, Tsiavaliaris G, Scholz T, Brenner B (2019) Transformation of the Nonprocessive Fast Skeletal Myosin II into a Processive Motor. Small 15: e1804313
- Nayak A*, Reck A, Morsczeck C, Muller S (2017) Flightless-I governs cell fate by recruiting the SUMO isopeptidase SENP3 to distinct HOX genes. Epigenetics Chromatin 10: 15
- Jung J, Nayak A, Schaeffer V, Starzetz T, Kirsch AK, Muller S, Dikic I, Mittelbronn M, Behrends C (2017) Multiplex image-based autophagy RNAi screening identifies SMCR8 as ULK1 kinase activity and gene expression regulator. Elife 6
- Nayak A, Muller S (2014) SUMO-specific proteases/isopeptidases: SENPs and beyond. Genome Biol 15: 422
- Nayak A, Viale-Bouroncle S, Morsczeck C, Muller S (2014) The SUMO-specific isopeptidase SENP3 regulates MLL1/MLL2 methyltransferase complexes and controls osteogenic differentiation. Mol Cell 55: 47-58
- Raman N, Nayak A, Muller S (2014) mTOR signaling regulates nucleolar targeting of the SUMO-specific isopeptidase SENP3. Mol Cell Biol 34: 4474-84
- Nayak A, Glockner-Pagel J, Vaeth M, Schumann JE, Buttmann M, Bopp T, Schmitt E, Serfling E, 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: 10935-46
Collaboration
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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. 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
- Dr. Julien Gondin
Institut NeuroMyoGène (INMG) Physiopathologie et Génétique du Neurone et du Muscle (PGNM) UMR CNRS 5261 – INSERM U1315, Lyon, France. -
Prof. Dr. med. Michael Heuser
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School - Prof. Dr. Christian Bär
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Germany
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