Division of Hematology Oncology
The core of our basic science research occurs within the Department of Cancer and Cell Biology, where scientists focus on understanding the molecular basis of cancer, with the overall goal of developing new and better treatments for the disease.
Interests of the research faculty include molecular biology of red cell differentiation, genetic epidemiology of lung cancer and the relationship between cancer and metabolic diseases such as diabetes and obesity.
The Division of Hematology Oncology is directly involved with UC cancer clinical trials. In addition, the division is involved in a number of programs and research projects. Key research activities include:
Experimental Therapeutics Program:
The Experimental Therapeutics Program is a phase-1 clinical trial unit based at the University of Cincinnati Cancer Institute. Led by John C. Morris, MD, the program offers discovery-driven new cancer treatment options only available in an experimental (phase-1) clinical trial setting.
Phase-1 clinical research trials are the first step in moving tested scientific concepts from the laboratory bench to bedside. Phase-1 trials are intended to evaluate safe dosages, method of administration (oral or injection) and treatment frequency. Trials typically include less than 50 people and therapy is administered in both an inpatient and outpatient setting.
Gene Therapy Strategies for Cancer:
John C. Morris, MD, and Jason C. Steel, PhD, focus on the development of therapeutic strategies for lung cancer and the use of immune stimulating cytokines and vaccines to stimulate the immune system to prevent or destroy cancer. They have focused on targeting lung cancer stem cells.
Theragnostic Drug and Biomarker Discovery and Development:
Xiaoyang Qi, PhD, focuses his research on developing a new saposin C coupled dioleoylphosphatidylserine (DOPS) nanovesicle which has the potential to offer a targeted, potent, broad and safe therapeutic agent for cancer patients. Sap C-DOPS nanovesicles preferentially induce apoptotic cell dealth in cancerous cells via a ceramide and caspase mediated pathway.
In preclinical studies, these nanovesicles have shown tumor-specific targeting activity and cancer-selective killing efficacy with significant inhibition of tumor growth in various animal tumor models. SapC-DOPS has striking absence of toxicity and adverse side effects in animals.
Red Cell Physiology:
The research of Robert Franco, PhD, focuses on the importance of red cell lifespan in diabetes and sickle cell disease, time-dependent in vivo red cell changes in sickle cell disease, mechanism of phosphatidylserine externalization is sickle cell disease and cancer.
In the Translational Research Core, Hassana Fathallah, PhD, focuses on developing biochemical, molecular or cellular assays that are tailored to a specific translational research question associated with a specific clinical trial. Her research encourages, supports and facilitates the interactions between biomedical investigators, surgeons and clinicians by collaborating and data sharing in order to accelerate the process of applying discoveries generated during research in the laboratory, and in preclinical studies, to the development of trials and studies in humans.
Led by Hassana Fathallah, PhD, the Cancer Institute Tumor Bank (CITB) at the University of Cincinnati is a response to an expressed need of scientific investigators for better access to human specimen samples needed in their research efforts. Our tumor banking operations include more than 3000 specimen.
CITB operates in a highly standardized manner to achieve uniformity of the performance and high quality. CITB enforces ethics and tissue usage requirements. Pertinent information about patients with cancer and their disease are also compiled. In an effort to establish a centralized, world class cancer tissue resource, CITB collaborates with different groups to ensure state-of-the-art banking operations.
Gene Regulation/Sickle Cell Disease:
The lab of Hassana Fathallah, PhD, focuses on the regulation of globin gene expression. In patients with sickle cell disease and beta-thalassemia, the adult hemoglobin is defective and inducing the expression of fetal hemoglobin by pharmaceutical agents will benefit these patients. Their research goals are better understanding of the mechanism of switching from fetal to adult hemoglobin and identification of new therapeutic targets for the treatment of patients with sickle cell disease and beta-thalassemia.
In the laboratory, they develop and apply new approaches to study the role of epigenetics, post-translational and post-transcriptional modifications in gene regulation.
The laboratory of Zhongyun Dong, PhD, focuses on the following areas:
- Prostate cancer biology: They determined and demonstrated that TGF-b-regulated IL8 expression may contribute to prostate cancer progression.
- Angiogenesis: they showed that adenoviral vector-mediated intratumoral delivery of IFN-b gene could significantly inhibit angiogenesis in animal model of human prostate cancer and that IFN-b or its gene could be an effective therapy for advanced prostate cancer.
- Prostate cancer therapy: a) they identified a novel androgen receptor antagonist that may serve as a lead compound for developing novel therapeutic drugs for advanced prostate cancer; b) they identified a series of the first-in-class and the only small molecule PCNA inhibitors which may be useful for studying PCNA function and the lead compounds for development of PCNA-targeting cancer therapy.
Hemostasis Research Program:
In the laboratory of Vladimir Bogdanov, PhD, the research currently under way focuses on two major areas spanning the fields of vascular biology, cancer research, and post-transcriptional regulation of Tissue Factor (TF) expression.
The first area comprises the studies examining the functions of TF splice variants in the vasculature and role they play in such disease states as thrombosis, cancer progression, and their combination – a common occurrence in certain malignancies. The second area comprises the studies of post-transcriptional regulation of TF expression in several cell types including monocytes/macrophages, known to extensively utilize alternative splicing to carry out a large variety of functions.
Cancer Drug Resistance:
In the laboratory of El Mustapha Bahassi, PhD, the focus is using genetic principles to understand cancer biology and then use the information to change the way patients are treated. He uses synthetic lethality and other genetic principles such as oncogene addition and genetic interaction mapping to identify novel mechanisms of cancer drug resistance, as well as identifying novel drug targets for therapy. The technologies he employs are diverse and include genome wide RNAi screens, chemical screens and whole genome sequencing.
Proteasome-based Therapies in Hematologic and Solid Tumors:
Currently, in the laboratory of James Driscoll, PhD, the focus of research is to:
- identify novel targets for the treatment of hematologic malignancies
- identify gene signatures that predict response to therapy
- to design novel therapeutic agents and translate our findings from the bench to the bedside.
With regard to the role of the mTOR/S6K pathway in diabetes, the laboratory of Sara Kozma, PhD, and Carol Mercer, PhD, has demonstrated that S6K1 is involved in regulating pancreatic beta cell development. Studies in Embryonic Stem Cells and in S6K1 knockout mice revealed the importance of S6K1 in controlling the commitment phase of adipogenesis in vivo. Her group is currently studying the role of mTOR signaling in hepatocellular carcinogenesis.
The results they obtained by using the therapeutic combination of RAD001 and BEZ235, targeting mTOR, in a mouse model of hepatocellular carcinoma, have triggered the initiation of a Phase 1B dose escalation trial with RAD001 combined with BEZ235 in patients with advanced solid tumors, performed at University of Cincinnati Cancer Institute.