1. Myogenesis and muscle regeneration. Investigating the molecular processes underlying muscle regeneration.

After injury, the skeletal muscle is capable of regeneration.  A population of resident stem cells (i.e., satellite cells) accounts for skeletal muscle plasticity, maintenance, and regeneration. Satellite cells are mitotically and physiologically quiescent in healthy muscles until stimulated by local damage. Accordingly, after a skeletal muscle injury, an intense regenerative program is initiated. The activated satellite cells migrate to the site of injury and become committed myoblasts, after which cell–cell fusion occurs, eventually creating multinucleated syncytium. To treat skeletal muscle diseases, muscular dystrophies, muscle mass loss associated with ageing or cancer, and to improve regeneration after sports injuries, it is essential to elucidate the signalling processes that influence the proliferation, differentiation and fusion of myoblasts formed by activation of skeletal muscle myogenic stem cells.

muscle diff
Effect of syndecan-4 silencing on muscle differentiation. Green: desmin, blue: nuclei.

 

CMLS összefoglaló

2. Investigation of signalling processes involved in cell polarity and cell migration. The role of exosomes.

ZSÓFI - kérlek szúrd be a Sybdecan-4 in tumor cell motility cikkből a rajzos migráció összefoglaló ábrát

In cells migration requires proper polarization, including the formation of leading and trailing edges, nucleus positioning, and the reorientation of cellular structures. It also depends on a front-to-rear calcium (Ca²⁺) gradient to regulate cell movement.
We found that silencing SDC4 (syndecan-4), a key proteoglycan, disrupts the polarization of migrating myoblasts (satellite stem cells). SDC4 knockdown abolished the Ca²⁺ gradient and centrosome reorientation, leading to reduced cell motility, migration distance, speed, and directional movement. We revaled futher changes in the actin cytoskeleton, including reduced branch numbers and lengths, highlighting SDC4's role in cell migration, particularly during muscle development and regeneration. For future studies we would like to know what role does SDC4 play in modulating cell motility.

https://pmc.ncbi.nlm.nih.gov/articles/PMC8268284/

 

3. Regulation of muscle mass. Search for new possibilities of local muscle mass augmentation.

Musculoskeletal atrophy can be associated with cancer, heart failure, immobilisation or ageing, among other conditions, and can also occur in the presence of denervation.

 

 

4. The metabolic role of skeletal muscle, skeletal muscle glucose metabolism, insulin resistance and diabetes mellitus.
Skeletal muscle is responsible for 40% of adult body weight and skeletal muscle plays a prominent role in metabolism. Skeletal muscle glucose uptake being responsible for 80-90% of the reduction in postprandial glucose levels. Our aim is to study novel signalling processes affecting skeletal muscle glucose uptake, identify potential drug targets, explore new therapeutic options for insulin resistance, and investigate early markers of diabetes. Musculoskeletal research is of paramount importance to improve the quality of life of an ageing society, to improve diabetes and insulin resistance, which are public health problems.

BARNABÁS kérlek írj néhány mondatot a zsírmáj eredményekről is, plusz a máj hisztológa fotók SudanIII

 

5. Oncogenesis in skeletal muscle: molecular processes and therapeutic opportunities

Rhabdomyosarcoma, the most common soft tissue sarcoma in children, arises from skeletal muscle cells that fail to differentiate terminally. As a result, instead of forming mature muscle tissue, the tumor cells grow uncontrollably. Studying how muscle cell differentiation is disrupted in RMS could help identify potential treatments that target these molecular mechanisms, either promoting normal muscle formation or preventing tumor cells from becoming more undifferentiated and cancerous.
Two subgroups of rhabdomyosarcoma, fusion-positive and fusion-negative rhabdomyosarcoma (FPRMS and FNRMS, respectively), are characterized by the presence or absence of the PAX3/7-FOXO1 fusion gene. Rhabdomyosarcomas frequently exhibit increased expression of human epidermal growth factor receptor-2 (HER2). Since HER2 is expressed in about half of rhabdomyosarcomas, the trastuzumab-mediated changes observed here may have therapeutic implications.

https://www.mdpi.com/1422-0067/26/5/2137
The role of syndecan-4 (SDC4) in rhabdomyosarcoma (RMS) and the effects of trastuzumab treatment on RD cells

 

6. Possibilities to reduce airway fibrosis, search for new antifibrotic agents.

ENIKŐ - ÖSSZEFOGLALÓ, FOTÓK