Co-Leader: Matthew D. Ringel, MD
Co-Leader: Philip Tsichlis, MD
The Cancer Biology (CB) Program, one of five trans-disciplinary, highly collaborative research programs at the OSUCCC – James, is highly productive with research encompassing basic and translational cancer biology for solid and liquid tumors. The overall goal of the CB Program is to define the mechanisms that cause cancer to develop, progress and become resistant to therapies to improve outcomes for patients with cancer.
CB Cancer Focus
- Lung cancer
- Colorectal cancer
- Breast cancer
- Thyroid cancer
- Cancer predisposition
- DNA damage repair
- Cancer development
- Therapeutic resistance
About CB Members
Leaders Drs. Tsichlis and Ringel have complementary expertise in basic and early translational cancer biology, defined roles as program leaders and work closely together in leading this program that is focused on fundamental discovery in cancer research and facilitating translation in multiple tumor types through collaborations.
CB is currently comprised of 57 faculty members from 19 departments across six colleges in the university. 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.
In the past five years, CB investigators have published 597 manuscripts, including 17% intra-programmatic, 35% inter-programmatic and 75% multi-institutional. Overall, 88% of publications are collaborative, with 123 papers having impact factors greater than 10, and 36 papers with impact factors greater than 15.
Key Program Objectives
Identify and define the roles of mutations in non-coding and coding regions of the genome in cancer biology.
This work has extended to the identification of new forms of non-coding RNAs and defining their scientific function, identifying germline and somatic changes in miRNA encoding genes or expression levels and defining their roles in cancer biology, identifying key regulatory pathways of non-coding RNA expression and/or cellular release, and translating that work into new diagnostics and therapeutics.
- Non-coding RNAs in cancer biology and treatment
- Genetic alternations that increase cancer risk
- Epigenetics and regulation of RNA in cancer biology
Studies using multicellular/tissue in vivo and in vitro models to enable a more complete understanding of cancer evolution from development to metastates.
This includes an understanding of tumor heterogeneity and tumor-host interactions. CB investigators have developed complex systems and used these to make fundamental discoveries identifying regulators of these processes, many of which emphasize on immune-tumor cell interactions.
- Models of cancer evolution
- Tumor microenvironment and immuno-oncology
- Cancer cell-autonomous mouse models
Identifying changes in cancer cells in response to therapeutic challenges and using this information to improve treatments through translational work with other OSUCCC programs.
There is specific focus on DNA damage repair responses to radiation and chemotherapies, cellular responses to hypoxia and response to targeted therapy, as well as cytokines in conjunction with growth in immuno-oncology.
- Resistance and response to DNA damage
- MicroRNAs and cell signaling in therapeutic response and resistance
- In vivo models and predictors of therapeutic response and resistance
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
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
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
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 immune-tumor cell interactions in cancer progression
- Cancer engineering and tissue microenvironment systems
- Collaborate across cancer centers to identify genetically homogenous subsets of cancer patients