Due to the significant limitations of randomized trials of pancreas cancer, we have been unable to answer many relevant questions in the management of patients with pancreas cancer. Recognizing these limitations. I founded and direct the Central Pancreas Consortium – a collaborative of eight, high volume pancreas centers that combine their data in an effort to provide meaningful, multi-center, high-volume outcomes data which is more clinically relevant. We have been able to provide compelling evidence that is now changing the treatment course for patients with pancreas cancer. I am the founder and director of this consortium.

 Overexpression of Src is associated with tumor progression and metastasis. Our study shows that the cellular localization of Src impacts survival in patients with pancreatic cancer. The results establish a rationale for Src inhibition as a therapeutic target in the treatment of pancreatic cancer. Further, we have identified potential biomarkers of resistance to Src inhibition.

Src family kinase (SFK)-targeting agents are currently undergoing clinical investigation for treatment of solid malignancies. We have identified that epidermal growth factor receptor (EGFR)-independent phosphorylation of STAT3 (pSTAT3) has been identified as a mechanism of tumor resistance to agents targeting SFK. Tumor pSTAT3 levels may be an important indicator of EGFR- and SFK-targeted antitumor treatment efficacy.

Investigated a novel mechanistic insights into ectodomain shedding of EGFR ligands. Amphiregulin-dependent signaling pathway that mediates the oncogenic effects of secondary bile acids in gastrointestinal cancers, the targeting of which may enhance therapeutic responses in their treatment.

Activated STAT3 is a biomarker of therapeutic resistance in pancreatic cancer (PDAC). Using PKT (Ptf1acre/+;LSL-KrasG12D/+;Tgfbr2flox/flox) genetic mouse model and in flank and orthotopic xenograft models of PDAC, we found that the combination of STAT3 inhibition and gemcitabine enhanced drug delivery to the tumor by stromal remodeling, a key strategy that can be utilized to improve therapeutic response. Additionally, combination of STAT3 and MEK inhibition altered the PDAC immune microenvironment by decreasing the number of infiltrating MDSCs and tumor promoting macrophages.