Developmental Research Program

Developmental Research Program

Jean-Pierre Issa, MD

Peter Jones, PhD

The specific objectives of the Developmental Research Program are to:

1. Publicize the availability of funds for pilot translational research studies in the field of Epigenetic Therapy for cancers.
2. Identify through this mechanism innovative projects with significant potential for developing and improving Epigenetic Therapies for cancers.
3. Encourage collaborations of projects with scientists within the SPORE and outside the SPORE, specifically the Van Andel Institute-Stand Up To Cancer Epigenetics Dream Team (VAI-SU2C).
4. Enhance the communication between the SPORE leaders and VAI-SU2C Investigators to encourage the development of innovative epigenetics therapies for cancer.
5. Ensure program flexibility so that developmental projects that show promise can be: 1) funded for a second year; 2) encouraged to apply for peer-reviewed funding (i.e. R01); or 3) expanded to become full SPORE projects.

To achieve our aims, we will establish 1) specific criteria for selection and funding through a peer review mechanism, and 2) mechanisms for close monitoring of, and collaboration between the SPORE leaders and program awardees to enhance the quality of the translational research goals.

AWARDEES

Heather M. O'Hagan, PhD

Indiana University School of Medicine

Using epigenetic therapy to target enteroendocrine cells in mucinous colorectal cancer

Mucinous colorectal cancer (CRC) makes up 10-20% of total CRC and has distinct clinical features and molecular alterations from non-mucinous CRC. Responses of mucinous CRC to conventional chemotherapy are dramatically inferior when compared to non-mucinous CRC, resulting in a need for the development of new therapeutic approaches. We have determined that secretory enteroendocrine cells, in addition to goblet cells, are enriched in and drive mucinous BRAF mutant CRC. Our overall goal is to determine an epigenetic therapy approach for mucinous CRC that uses epigenetic inhibitors to target secretory cells and reduce tumorigenesis. To accomplish this goal, we will use our recently developed model of in situ mucinous BRAF mutant CRC to determine the effect of lysine demethylase 1 (LSD1) and DNA methyltransferase inhibition on tumor secretory cell content, the tumor immune microenvironment and colon tumorigenesis.

Roberto Pili, MD

University at Buffalo

Developing HDAC inhibitors as immunomodulators

Histone deacetylase (HDAC) inhibitors represent a class of agents with potential antitumor activity due to modulation of both transcriptional and non-transcriptional gene regulation. The goal of this project is to determine the immunomodulatory activity and therapeutic potential of HDAC inhibition in the setting of immunotherapies. We hypothesize that HDAC inhibition modulates the immune response and improves/restores the antitumor activity of immunotherapies. It is expected that these preclinical and clinical studies will provide: 1) Evidence that combining HDAC inhibitors and immunotherapies increases the antitumor effects 2) Insight on the role of HDACs in the modulation of specific immune cell subtypes 3) Foundation for future clinical trials in patients with renal cell carcinoma and other tumor types.