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The Makarenkova Lab

Research Overview

Skeletal muscle atrophy is a devastating disorder that occurs in a  large number of chronic diseases such as cancer, diabetes, trauma, cystic fibrosis, HIV, aging and genetic disorders. Research in my laboratory focuses on the mechanisms of muscle regeneration and regulation of satellite cell function.  Satellite cells are muscle progenitor cells, which reside in skeletal muscle and are the main reserve of repairing damaged skeletal muscle.

Muscle development and regeneration

We have recently shown that that homeobox transcription factor Barx2 is a new important component of the muscle molecular program controlling the expansion and differentiation of satellite cells and other muscle progenitors during muscle regeneration.

Moreover, we have also shown that Barx2 is an important functional component of SC activation: Barx2 regulates SC cytoskeletal re-arrangement, migration, proliferation, and fusion. In addition, Barx2 regulates plasticity of immature myofibers and might act as a molecular switch in controlling cell differentiation and proliferation. The molecular mechanisms underlying this fascinating phenomenon are still largely unknown. Thus Barx2 is a unique factor because it can influence both conventional mammalian satellite cell-mediated muscle repair and also a dedifferentiation pathway that is similar to what is observed in lower vertebrates.

Promoting muscle regeneration by manipulating the functions of endogenous muscle stem cells is a promising therapeutic approach for diseases such as muscular dystrophy. Our goal is to develop the new insights that can improve myoblast transplantation efficiency and muscle repair.

Molecular mechanisms of muscle development and regeneration.

Dry eyes occur when the lacrimal glands produce an inadequate supply of tears. Dry eyes can occur at any time in life, as a result of autoimmune disorder, allergy, infection or trauma, however aging is one of the most common causes of dry eyes. Dry eye condition is usually chronic, and it affects both eyes. Dry eyes can lead to progressive corneal ulceration, scarring and blindness.
Our goal is to understand the mechanisms of lacrimal gland development and regeneration. Specifically, we are interested in growth factors/extracellular matrix signaling, lacrimal gland progenitor cell specification and function, and the transcriptional regulation of branching morphogenesis. Our previous studies have shown that members of the (FGF) family are important regulators of lacrimal gland morphogenesis. In particular, we have found that FGF-10 is necessary for lacrimal and Harderian gland development. Recently we have made significant progress in understanding how structural differences in various FGFs are incorporated into their functional properties. Thus we have shown that differences in the binding of FGF7 and FGF10 to heparan sulfate (HS) within the extracellular matrix result in the formation of different gradients that dictate distinct functional activities of these FGFs during branching morphogenesis. Our studies show how structural differences within FGFs are connected with their biological function in branching morphogenesis. In addition, we are also assessing downstream activation of multiple signaling pathways as well as cellular proliferation to understand regulatory mechanisms of branching morphogenesis. Furthermore, we isolate and culture the lacrimal gland progenitor cells. We are also testing different factors that can improve survival and expansion of lacrimal gland progenitor cell cultures.

Our long-term goal is to develop therapeutic approaches for the regeneration of damaged human lacrimal gland.