Principal Investigator: Joseph Rutkowski, Phd
Institution: Texas A&M Health Sciences Center
LF Funding History: 2017 Postdoctoral Fellowship Award
Hypothesis: We hypothesize that increased adipose tissue growth in a VEGF-D mouse model will result in altered lymphatic density, nerve function, inflammatory profile that would contribute towards understanding lipedema physiology
Current LF Collaborations:
Collaborative Opportunities: There is always a desire to translate or realize our basic discoveries in the clinic, and to use patient samples to develop better models of the basic pathology of lipedema. Our laboratory is equipped to analyze many samples forms using different modalities. We thus seek available, well-diagnosed tissue samples, fluids, cells, etc. from lipedema patients. Most relevant to our Lipedema Foundation project are tissue blocks/biopsies of adipose tissue and skin from defined patients and weight-matched controls for descriptive and quantitative identification of lymphatic, immune, and neuronal cells populations and matrix composition.
We are also active in many tissue pathologies of inflammation-associated lymphangiogenesis and lymphatic malformations beyond adipose tissue and constantly seeking collaborators interested in work in underappreciated and rare diseases.
Related Links: Rutkowski Lab
Project: VEGF-D Induced Lymphangiogenesis; a Novel Approach to Tackle Dysfunctional Adipose Tissue in Lipedema
Lipedema is the aberrant expansion of subcutaneous adipose tissues that are not responsive to weight loss. These tissues are clinically characterized by inflammation, fibrosis, and a local dysfunction of lymphatic vessels and are often described by patients as being painful. These features are likely to be critically linked: properly functional lymphatic vessels are necessary for the resolution of chronic inflammation.
We propose to use a novel mouse model of adipose tissue specific lymphatic vessel expansion (lymphangiogenesis). Lymphangiogenesis is regulated by signaling through a protein receptor, vascular endothelial growth factor receptor-3 (VEGFR-3) in growth, development, and inflammation. Coincidentally, VEGFR-3 signaling has also been identified in nerve cell population. Our mouse model that uses VEGF-D expression, a specific ligand for VEGFR-3, thus may provide the additional clinically relevant feature of altered nerve density and function in adipose tissue.
We will thus seek to correlate how VEGF-D alters adipose lymphatic density, nerve function, and inflammation in our mouse model during obese adipose expansion and will characterize these features in human lipedema adipose and skin samples. In total, our work will identify the underlying physiological mechanisms of lipedema to establish biological targets for clinical therapy.