Our laboratory investigates growth factor and cytokine signaling in tissue fibrosis. We have recently identified the TGF-β1/ADAM10/Ephrin-B2 pathway as a major driver of fibroblast activation in lung, skin and tumor fibrosis.

Matrix stiffness and mechanical forces promote tissue fibrosis via mechano-activation of fibroblasts. Our laboratory investigates mechanotransduction pathways including integrin, FAK, ROCK, YAP/TAZ pathways in fibrotic diseases and tumors.

Evasion of apoptosis leads to myofibroblast persistence and fibrosis. We are investigating mechanisms promoting myofibroblast resistance to apoptosis and cellular senescence in the aging-associated disease of idiopathic pulmonary fibrosis.

Desmoplastic tumors including pancreatic cancer are characterized by a dense fibrotic stroma. We are investigating mechanisms by which cancer associated fibroblasts promote fibrosis and tumor growth.

Our laboratory utilizes preclinical mouse models of lung, skin, liver, kidney and pancreatic fibrotic disease to investigate pathological disease mechanisms and to evaluate therapeutic efficacy of anti-inflammatory and anti-fibrotic drugs in vivo.

Our laboratory uses CRISPR/Cas9 gene editing tools to investigate pro-fibrotic pathways. We use a knock-in Cas9 transgenic mouse to validate pathways and therapeutic targets in vivo in our preclinical murine models.

Our laboratory investigates mechanobiology of fibrosis and tumors by bioengineering matrices with tunable matrix stiffness. We also employ photolithography to fabricate micropatterned hydrogels.

Our laboratory employs atomic force microscopy (AFM) to measure mechanical properties of murine and human tissues with nanoscale spatial resolution. We are interested in matrix stiffness and topography.

Our laboratory uses cutting-edge technologies such as single cell RNA sequencing, proteomics and metabolomics to understand fibroblast heterogeneity in fibrosis as well as the effect of anti-fibrotic drugs on specific subsets of fibroblasts and epithelial cells.

Our laboratory uses a functional assay called “BH3 profiling” to understand apoptosis sensitivity and cell survival pathways. We use BH3 profiling in combination with cell death analyses to assess the ability of drugs to induce apoptosis of pathological cells in fibrosis.

Our laboratory has developed high throughput screening assays to identify drugs with the ability to inhibit myofibroblast activation or induce their apoptosis. We collaborate with the Harvard Screening Facility to run small molecule, siRNA and miRNA libraries in our cell-based phenotypic screening assays.

Human precision cut tissue slices are emerging as ex vivo models for studying human cell biology and novel drug compounds. We use our Compresstome® to generate precision cut lung slices (PCLS) as 3D tissue cultures. We use tissues from patients with lung fibrosis and other fibrotic diseases.