Two awards to advance pancreatic cancer research

The Pancreatic Cancer Action Network and the American Association for Cancer Research have awarded Stephanie K. Dougan, Ph.D., postdoctoral fellow at the Whitehead Institute for Biomedical Research, and Oliver G. McDonald, M.D., Ph.D., postdoctoral fellow at Johns Hopkins University, the 2012 Pancreatic Cancer Action Network-AACR Pathway to Leadership Grants.

These five-year grants, each providing $600,000 in research funding, will be formally awarded at the AACR Annual Meeting 2012, held here March 31 - April 4.

"With the partnership of the Pancreatic Cancer Action Network, we are able to provide these grants to encourage gifted, young researchers such as Dr. Dougan and Dr. McDonald to pursue their research endeavors and advance the field," said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the American Association for Cancer Research. "Their projects have the potential to lead to breakthroughs that better prevent, detect and treat pancreatic cancer."

"As the Pancreatic Cancer Action Network works diligently to double the survival rate of pancreatic cancer by 2020, it is critical that we fund the very best science and brightest minds to ensure scientific progress is made. We are honored to welcome Drs. Dougan and McDonald to the team and to our robust community of pancreatic cancer researchers," stated Lynn Matrisian, Ph.D., Pancreatic Cancer Action Network's vice president of scientific and medical affairs. "We look forward to interacting with Drs. Dougan and McDonald and trust that the Pathway to Leadership Grant will accelerate progress toward improved patient outcomes."

The Pathway to Leadership Grant, intended for postdoctoral or clinical research fellows, parallels the highly coveted K99/R00 early-career investigator awards offered by the National Institutes of Health. It provides financial support for two years of mentored research followed by three years of independent research.

The goals of the Pancreatic Cancer Action Network-AACR grants program are to build a robust pancreatic cancer research community; to encourage collaboration, information-sharing and innovation; and to expedite scientific and medical breakthroughs for patient benefit.

Funding decisions for the Pathway to Leadership Grant are made by a stellar committee of experts in pancreatic cancer using a rigorous and transparent process. In addition to receiving research funds, grant recipients are provided with career development opportunities. These include mentorships and connections with senior scientists in the field; invitations to present at scientific sessions, lead conference workshops, and participate in training and educational webinars; involvement with pancreatic cancer survivors and their caregivers; and resources to keep them apprised of emerging developments in the field.

2012 Pathway to Leadership Grant Recipients:

Dougan's research, "Transnuclear mice: Understanding the T cell response to pancreatic cancer," proposes to generate an innovative mouse model (called TN) of pancreatic cancer with alterations to the immune system. In this TN mouse model, cytotoxic (or killer) T cells of the immune system will be programmed to recognize a protein present in pancreatic cancer cells, mesothelin. The mice will also allow Dougan to investigate the balance between cytotoxic T cells trained to attack pancreatic cancer and regulatory T cells that would otherwise impede the immune response.

Dougan believes that immunotherapy represents a very attractive approach for pancreatic cancer treatment. Through the creation of TN mice, Dougan aims to identify mechanisms to inhibit the immunosuppressive regulatory T cell response, in turn resulting in an increased population of cytotoxic T cells and a heightened immune response generated against the cancer.

"This novel approach will not only generate many lines of useful mouse models, but also identify the specificity of regulatory T cells for the first time, and may help address why these cells home so readily to pancreatic tumors and block the body's innate immune response to the tumor," Dougan said. "Such information will allow us to create targeted therapies to suppress or eliminate regulatory T cells specifically while promoting cytotoxic T cell function."

This research will serve as the foundation of Dougan's independent research program.

McDonald's research, "Genome-wide epigenetic reprogramming during evolution of pancreatic cancer," will investigate non-sequence related genetic or epigenetic events that induce cellular changes necessary for the onset and eventual metastasis (spread) of human pancreatic cancer.

Previous studies conducted by McDonald and colleagues have mapped the function of various epigenetic modifications that accompany pivotal cellular changes. For example, normal cells of the pancreas would not have the ability to depart the pancreas or survive in the bloodstream, but cancer cells are able to adopt these characteristics. Such modifications represent survival mechanisms exhibited by cancer cells as these epigenetic changes facilitate cell movement necessary for metastasis, as well as chemotherapeutic resistance. By understanding the nature of such modifications and the mechanisms involved in their establishment, McDonald and his colleagues hope to identify key regulators of pancreatic cancer reprogramming, metastasis and resistance to chemotherapy.

"These seminal studies will provide unprecedented insights into epigenetic reprogramming during pancreatic cancer evolution," said McDonald. "The findings will have far-reaching implications, and will pave the way for development of novel diagnostics and therapeutics for pancreatic cancer."