Connective Tissue Biology
Connective tissue provides structure and support to every organ, joint, and vessel in the body. It is composed of a complex network of cells, proteins, and extracellular matrix that together maintain strength and flexibility. In the Ehlers-Danlos syndromes, disruptions in connective tissue structure and signaling can lead to widespread symptoms affecting multiple systems. Our lab studies the biology of connective tissue to understand how these changes occur across EDS subtypes, including hypermobile EDS (hEDS), with the goal of identifying what makes these tissues behave differently.
KLK Gene family
One candidate gene family was thoroughly investigated for being a potential genetic driver of hEDS because of its integral role across enzyme regulatory processes that affect connective tissue laxity and other symptomological manifestations of this condition. That family is the Kallikrein (KLK) gene family, which is implicated in regulating proteolytic cascades that govern numerous biological processes, including extracellular matrix (ECM) remodeling, inflammation, vascular tone and autonomic regulation, connective tissue integrity, and endocrine signaling.
Proteomics
There is a clinical need for the development of diagnostic tools for hEDS and HSD. Using plasma and serum samples from hEDS and HSD patients, we are using proteomic approaches to identify potential biomarkers that can be used to develop an accurate and sensitive diagnostic test. This would improve diagnostic capabilities and allow for earlier and accurate diagnosis in people with hEDS and HSD.
Mast Cell Activation
Frequently observed with EDS is Mast Cell Activation Syndrome (MCAS), characterized by heightened mast cell activity and degranulation, resulting in a range of allergic symptoms. We are working to understand the intricate connection between connective tissue dysfunction and mast cell activation. Our aim is to enhance the management of both MCAS and EDS, offering a more comprehensive approach to improving the lives of affected by these conditions
Rare EDS Types
While hEDS is not considered a rare disease, the other subtypes of EDS are exceeding rare, with some subtypes only reported in a few families worldwide. Research on these conditions is lacking, even in cases where the genetic cause is known. We are interested in studying the underlying biology of rare subtypes of EDS, and have developed a mouse model repository to do so.
Dermatological Pathologies
hEDS patients are known to have weak connective tissue, leading to joint hypermobility and instability. To understand the altered connective tissue present in hEDS patients, we are using a variety of biological models including in vitro and in vivo systems. We are analyzing the expression of key proteins involved in connective tissue formation and maintenance, such as collagen, elastin, and enzymes involved in post-translational modifications to look for differences in protein expression patterns. Insights from these studies will guide further research into the biological mechanisms behind hEDS.