Organ Development and Tissue Regeneration

The goal of regenerative medicine is to build body parts to correct birth defects in newborns or replace body parts in the aging. Mammalian cells that are reset to the proper developmental state appear to have the ability to integrate into aged or improperly formed tissues and organs. Such reprogrammed cells may potentially form replacement body parts. Prior to realizing this potential, it will be necessary to understand the underlying mechanisms that mammalian genomes use to create the many cell, tissue, and organ types of mammals. Cell types are defined at the molecular level during embryogenesis by a process called pattern formation. The Kioussi lab is interested to study the developmental programs that define the sets of genes available to each particular cell type in the body, and the biochemical signaling interactions used at any given time and place.

Myogenesis - Congenital myopathies and muscular dystrophies cause reduction of muscle size, loss of muscle tone, muscle weakness and locomotive disabilities. During embryogenesis, sequential phases of myogenesis lead to the formation of the skeletal musculature. We study the transcriptional regulation of gene expression that is involved in pattern formation and the commitment of undifferentiated cells to specific developmental pathways.

Cardiogenesis - Congenital heart defects in humans occur in approximately 1% of live births and are a leading cause of miscarriages. Gene mutations thataffect the formation of the heart, lead to congenital malformations. One of the most important reasons for this high incidence in congenital heart defects is that the heart is the first organ to form and must be active at all stages as it develops its remarkably complex structure. We try to understand the mechanisms of many human congenital cardiac syndromes and defects at the cellular and molecular level, which ultimately lead to treatments and cures.

Cell Reprogramming - Adult somatic cells are tightly fixed into stable cellular states by epigenetic mechanisms that consolidate the transcriptional network states achieved during pattern formation in embryogenesis.  The sustained artificial expression of specific combinations of transcription factors can eventually reprogram cells to a different developmental state.  We are trying to convert adult biopsy cell cultures into specific neurons, muscles or cardiomyocytes.  We are creating co-expression systems to transiently sustain specific combinations of transcription factors in biopsied cells to test the idea that reprogramming can occur directly to other cell types. This would considerably simplify creation of specific cell types for medical applications and would directly test the hypothesis that transcriptional network states specify cell types during pattern formation.