Co-Leader: Matthew D. Ringel, MD
Co-Leader: Gina M. Sizemore, PhD
Co-Leader: Dawn S. Chandler, PhD
The overall vision of the CB Program is to exploit the fundamental mechanistic knowledge to improve cancer prevention, treatment, and outcomes through collaborations.
The CB Program is dedicated to improving cancer outcomes by translating basic science discoveries through collaboration. Key discoveries have resulted in improved colon and endometrial cancer risk assessment and detection; development of lung and thyroid cancer prognostic markers, identification of therapeutic targets for leukemia, and development of breast cancer prognostic markers. By supporting science in its thematic areas and facilitating translation for OSUCCC initiatives, the CB Program provides high-impact translational science to improve the care of patients with cancer.
CB Cancer Focus
- Lung cancer
- Colorectal cancer
- Breast cancer
- Thyroid cancer
- Chronic lymphocytic leukemia
- Acute myeloid leukemia
- Immuno-oncology
- Cancer predisposition
- microRNAs
- DNA damage repair
- Cancer engineering
About CB Members
Investigators focus on three thematic areas: 1) Defining the roles of non-coding RNAs, gene mutations, and regulation of gene expression in cancer development and progression; 2) Determining new mechanisms of altered cancer cell signal transduction and DNA damage responses, as well as responses to therapeutic challenges; and 3) Integrating cancer biology into complex model systems, computational biology, and human tissues to study mechanisms of cancer progression. Program members are internationally recognized as scientific leaders within these research themes.
Matthew D. Ringel, MD, Gina M. Sizemore, PhD and Dawn S. Chandler, PhD serve as co-leaders of the CB Program.
The CB Program is currently comprised of 56 faculty members from 21 departments across five colleges in the university (Arts and Sciences, Engineering, Medicine, Public Health and Veterinary Medicine). CB membership includes two members of the National Academy of Sciences, three members of ASCI and AAP, editors and past editors of top-tier journals such as Journal of Immunology and Cancer Research, leaders of national guidelines committees and national and international meetings, and members who chair or are standing members or ad-hoc reviewers for NIH study sections.
CB investigators have published 645 papers, including 35 percent that are intra- or inter-programmatic and 73 percent multi-institutional. Overall, 81 percent of publications are collaborative. Of these, 82 were published in journals with an impact factor (IF) >10, and 42 in journals with an IF >15.
Key Program Objectives
Aim 1: Mechanisms of cancer initiation
Studies focus on identification and characterization of mutations, epigenetic changes, and the expression and function of coding and non-coding genes. The goal will be to discover novel mechanisms of cancer predisposition and initiation, with an emphasis on translation.
Aim 2: Mechanisms and markers of response and resistance to therapeutic and environmental challenges
Studies focus on cancer responses to radiation, cytotoxic chemotherapy, and targeted therapy with emphasis on signaling, DNA damage responses and the response to hypoxia and anti-tumor immunity.
Aim 3: Mechanisms of cancer progression
Studies focus on the identification of potentially targetable mechanisms that regulate tumor progression and metastasis.
Scientific Accomplishments
ERK Activation Globally Downregulates miRNAs Through Phosphorylating Exportin-5. An inter/intra-programmatic study defining a new mechanism of miR regulation by the ERK pathway fundamental for cancer development and progression. Published in Cancer Cell.
PIs: Kalpana Ghoshal, PhD; Carlos Croce, MD
MicroRNA-3151 Inactivates TP53 in BRAF-Mutated Human Malignancies. An inter-programmatic study identifying a novel micro-RNA-mediated regulatory mechanism for all BRAF-mutated human cancers. Published in Proceedings of the National Academy of Sciences of the United States of America.
PIs: William Carson III, MD; Albert de la Chapelle, MD, PhD
The Human PMR1 Endonuclease Stimulates Cell Motility by Down Regulating miR-200 Family microRNAs. An inter-programmatic study defining the mechanism by which a cancer-related endonuclease regulates cancer cell motility by regulation of an EMT-driving microRNA utilizing novel engineered methods. Published in Nucleic Acids Research.
PIs: L. James Lee, PhD; Daniel Shoenberg, PhD
Stromal PTEN Determines Mammary Epithelial Response to Radiotherapy. An inter- and intra-programmatic study defining the fundamental role of the tumor microenvironment in causing secondary breast cancer development via EGFR signaling. Published in Nature Communications
PIs: Gina Sizemore, PhD; Steven Sizemore, PhD; Arnab Chakravarti, MD; Peter Shields, MD; Julia White, MD
Papaverine and Its Derivatives Radiosensitize Solid Tumors by Inhibiting Mitochondrial Metabolism. An intra-programmatic collaborative study identifying new mechanisms and therapies for radiosensitization in cancer. Published in Proceedings of the National Academy of Sciences of the United States of America.
PIs: Ioanna Papandreou, PhD; Nicholas Denko, MD, PhD
Stress-Inducible Gene Atf3 in the Noncancer Host Cells Contributes to Chemotherapy-Exacerbated Breast Cancer Metastasis. A study identifying a novel role for altered immune-environment stress response to chemotherapy as a mediator of progression during chemotherapy in breast cancer. Published in Proceedings of the National Academy of Sciences of the United States of America.
PI: Tsonwin Hai, PhD
RAGE Mediates S100A7-Induced Breast Cancer Growth and Metastasis by Modulating the Tumor Microenvironment. An inter- and intra-programmatic collaborative study demonstrating the mechanism by which RAGE induces breast cancer progression and metastasis by through induction of tumor-associated macrophages. Published in Cancer Researcher.
PIs: Michael Ostrowski, PhD; Charles Shapiro, MD; William Carson III, MD; Ramesh Ganju, PhD
RCAN1-4 is a Thyroid Cancer Growth and Metastasis Suppressor. An inter-programmatic study identifying a new metastasis suppressor pathway that functions be facilitating an tumor inhibitor immune microenvironment. Published in JCI Insight.
PIs: Soledad Fernandez, PhD; Matthew Ringel, MD
Pyruvate Kinase M2 Regulates Homologous Recombination-Mediated DNA Double-Strand Break Repair. An inter/intra-program collaboration provides a new mechanism linking cellular metabolism to DNA repair. Published in Cell Research.
PIs: Gina Sizemore, PhD; Steven Sizemore, PhD; Arnab Chakravarti, MD
Future Directions
The following are some of the future key areas of focus for the CB Program:
- Advance preclinical development of miR-directed therapies
- Advance studies of tumor cell interactions with the immune system and their role in cancer progression
- Cancer engineering and tissue microenvironment
- Collaborate across cancer centers to identify subsets of cancer patients