Jones Laboratory

The Jones laboratory in The Department of Pathology and Laboratory Medicine at The University of Pennsylvania seeks to understand how the tissue microevironment, which includes the extracellular matrix (ECM), specifies 3-D form, and how this regulates gene expression and differentiated functions in the lung vasculature and breast epithelium. More specifically, we are determining how the oncofetal ECM protein tenascin-C (TN-C) is regulated at the transcriptional level by the Prx1 homeobox gene transcription factor during vessel formation in the fetal lung, as well as with the onset and progression of pulmonary arterial hypertension, an incurable lung disease. In addition to basic studies addressing the origins of PAH, Jones also directs The Penn-CMREF Center for Pulmonary Arterial Hypertension Research. This research unit is dedicated to harvesting, banking and disseminating human lung vascular cells from PAH patients from across the U.S. Overall, this unique, national resource, organized through The Pulmonary Hypertension Breakthrough Initiative, is allowing investigators to gain a deeper understanding of the genetic and epigenetic factors that contribute to PAH pathogenesis.

In parallel, our studies in the mammary gland focus on the role of stromal TN-C in regulating proto-oncogene function in the adjacent epithelium during breast tumorigenesis. Collectively, our studies have reinforced and advanced the once radical notion that phenotype can dominate over genotype. Given this, a detailed understanding of cell and tissue architecture will be required. In response to this, we collaborate with Jenny E Sabin at PennDesign, with whom Jones founded the Sabin+Jones LabStudio, a hybrid research and design unit based within The Institute for Medicine & Engineering (IME), and The Schools of Medicine (SOM) and Design (SOD) at UPenn. Within LabStudio, architectural designers, mathematicians, materials scientists and cell biologists actively collaborate to develop, analyze and abstract dynamic, biological systems through the generation and design of new tools. These new approaches for modeling complexity and visualizing large datasets are subsequently applied to both architectural and biomedical research and design.

Each of our research trajectories are underscored by a number of basic and pre-clinical projects including:

1. Understanding how Prx1 promotes vasculogenesis & angiogenesis in the developing lung (Matrix & cell biology)

2. Determining how Prx1 controls angiogenesis in the fetal lung via its effects on TN-C and Sonic Hedgehog (Shh) signaling (Signal transduction studies)

3. Elucidating how cytoskeletal-dependent vasoconstriction with the hypertensive pulmonary arterial wall promotes TN-C gene transcription via Prx1 (Cell & tissue mechanics)

4. Using nano-engineered surface chemistry to measure smooth muscle cell contractility, and to apply these principles to the design of a responsive macro-architecture (Nanoengineering, chemical engineering & design)

5. Identifying novel pathways and drugs regulating TN-C gene transcription (High throughput screening & gene promoter studies)

6. Using the PAH patient plasma proteome to develop novel, rapid and non-invasive diagnostic and prognostic tests (Proteomics & diagnostics)

7. Evaluating how tenascin-C contributes to proto-oncogene activation in breast cancer, as well as pulmonary metastasis (Extracellular matrix & breast cancer)

8. Developing novel modes of visualizing large, dynamic, multi-dimensional datasets in silico and at the human scale in multiple dimensions using a multimedia approach (Nonlinear systems biology, art & design)