2018 Funded Research Projects

Dr. Aatur Singhi | University of Pittsburgh

DNA-based testing of pancreatic cyst fluid (PCF) is a useful adjunct to the evaluation of pancreatic cysts (PCs). A prospective study was performed to evaluate preoperative PCF DNA testing.  Over 43-months, 626 PCF specimens from 595 patients were obtained by endoscopic ultrasound (EUS)- fine needle aspirations and assessed by targeted next-generation sequencing (NGS). A separate cohort of 159 PCF specimens was also evaluated for KRAS/GNAS mutations by Sanger sequencing.

Sky Foundation grant has helped fund the second version of PancreaSeq or PancreaSeqV2. PancreaSeqV2 makes significant improvements to the evaluation of human clinical pancreatic cyst samples to inclusion of additional genomic alterations involved in pancreatic cysts, pancreatic cancer and neuroendocrine neoplasms of the pancreas. Further, PancreaSeqV2 improves the sensitivity of detecting genomic alterations in pancreatic cyst fluid. Currently, PancreaSeqV2 is being validated on a retrospective cohort of 99 pancreatic cysts with our goal of implementing it clinically by early August.

 

Pancreatic Cancer Action Network: Early Detection Initiative

Pancreatic Cancer Action Network logo. (PRNewsFoto/Pancreatic Cancer Action Network)

The chance of survival when detecting pancreatic cancer early enough is 40% for up-to five years; but when discovered late there is less than a 5% survival rate.

The foundation of Early Detection Initiative (EDI) is timely completion of the New Onset of Diabetes (NOD) cohort and support related research to translate results into clinical practice.

25% of patients diagnosed with pancreatic cancer have experienced NOD. It is important to conduct a study with an enriched high risk population so that the study can be more focused. There have been studies conducted to reveal that 40-50% of pancreatic cancer patients have diabetes and 50-80% of these patients were diagnosed with NOD.

Goal

·    Create research dataset

·    Screen patients

·    Show stage shift

Design

·    10k patients, followed for 3 years

·    Recruit from Electronic Health Records (EHR) in integrated healthcare systems

·    Serial biospecimens to validate promising emerging biomarkers

·    Imaging CT or MRI

 

Research Update:

Research Committee is advancing preparations for the official launce of the EDI Initiative.

 

University of Michigan | Howard Crawford Laboratories

Immunotherapy

The Pasca di Magliano, Lyssiotis, Frankel and Crawford laboratories at the University of Michigan have teamed up to devise ways to make immunotherapy effective in fighting pancreatic cancer. Dr. Pasca di Magliano has discovered that macrophages, a specialized inflammatory cell, are the cells primarily responsible for establishing the immune suppressed environment by both sending signals to immune cells to ignore the tumor and then signaling to the tumor cells to have them express high levels of PD-L1.

In turn, the tumor cells instruct the macrophages to also make PD-L1. In an attempt to disrupt this cycle, Dr. Crawford has identified one of the primary molecules the macrophages use to turn on tumor cell PD-L1, known as HBEGF. Meanwhile, Dr. Lyssiotis has found that tumor cell metabolites are responsible for telling the macrophages to make PD-L1. With this knowledge in hand, Dr. Frankel, a surgeon who specializes in immunotherapy research, is involved in translating these observations to the clinic, combining immune checkpoint inhibitors with therapies to disrupt the cellular crosstalk responsible for establishing the immunosuppressive environment in preclinical models of human pancreatic cancer.

Immunotherapy Team Members

Marina Pasca di Magliano, PhD

Costas Lyssiotis, Phs

Timothy Frankel, MD

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