The scientists and clinical investigators in the Division of Hematology Oncology focus on understanding the molecular basis of cancer, with the overall goal of developing novel and improved cancer treatments. The Division of Hematology and Oncology interacts closely with the University of Cincinnati Cancer Center scientific and clinical programs.
Current research interests of the faculty include oncogene-depended intracellular signaling, leukemia targeted therapy, cancer metabolism, immuno-oncology, the role of tissue factor in pancreatic cancer, nanoparticle delivered therapeutics, and the design and execution of early phase clinical trials
Our current key research activities are briefly outlined below.
Experimental Therapeutics Program:
Director: Davendra Sohal, MD; Physicians: Trisha Wise-Draper, Emily Curran, MD, Shuchi Gulati, MD.
The Division offers a wide portfolio of clinical trials that bring new cancer drugs to the clinic. The Experimental Therapeutics Program conducts phase-1 and early phase clinical trials at the University of Cincinnati Cancer Center. These types of trials are the first step in moving new pharmaceutical compounds, often developed by UC scientists, and are intended to evaluate safe dosages, method of administration and potential anti-tumor effects. In addition, the Experimental Therapeutic Program co-ordinates the execution of later phase clinical trials that are sponsored by federal agencies, private foundations, pharmaceutical companies, and private entities. These trials are conducted to determine whether a new drug is efficacious.
Cancer Signaling and Lipidomics:
The laboratory of Dr. Scaglioni, MD, integrates the use of mouse cancer models, cancer cell lines, small molecule inhibitors, RNAi, and CRISPR technologies to identify cancer networks that represent novel targets for therapy. The focus of research is the KRAS and MYC oncogenes, which play a pivotal role in cancer. Current efforts focus on the role of lipid metabolism in the regulation of ferroptosis, response to targeted cancer therapy, and emergence of drug resistance. The lab has identified several cellular networks that represent novel therapeutic targets in lung cancer, such as focal adhesion kinase, the XPOI nuclear export receptor the SUMO E3 ligase PIAS1 is a critical regular of MYC and of the PML-RARA oncogenes. These findings led to several clinical trials (NCI identifiers NCT01951690, NCT03095612).
Overcoming Immunotherapy Resistance:
The laboratory of Drs. Wise-Draper and Takiar primarily focuses on mechanisms that mediate therapeutic resistance in Head and Neck Squamous Cell Carcinoma and Adenoid Cystic Carcinoma. Using patient samples including blood and tumor tissue from clinical trials before and after therapy (radiation, targeted drugs, immunotherapy, etc.) allows for a unique opportunity to study the positive and negative effects of treatment on tumor cell signaling, molecular changes, genomics as well as impact on the cancer microenvironment. Proper handling of clinical trial specimens for downstream analysis is a particular focus funded by a current U01. The laboratory utilizes patient derived organoids (PDO) combined with autologous peripheral and/or tumor derived immune cells to study possible therapies to overcome resistance identified in patient samples. Specific projects include B cell contribution to immunotherapy response, B7-H3 mediated T cell inhibition, and natural killer cell mediated IL-9 regulation. Several clinical trials for which samples are obtained are ongoing and new trials have been developed from these preclinical findings (NCI identifiers NCT02641093, NCT03122197, NCT03355560, NCT02325401, NCT04414540, NCT04313504, NCT05074940).
Leukemia and Drug Development Laboratory
The laboratory of Dr. John C. Byrd and Dr. Erin Hertlein is working collaboratively to understand the molecular underpinnings of development and progression of chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and their precursor diseases (MBL, MDS, and clonal hematopoiesis). With access to primary tumor cells and spontaneous mouse models of these diseases, we also investigate the interplay of leukemia with the immune system and microenvironment. Areas of mechanistic focus include the role of select genes that drive resistance to targeted therapy, and strategies to enhance immune activation while eliminating leukemia immune evasion. We are also developing pharmacological strategies to exploit hematopoietic differentiation and tumor metabolism to enhance targeted therapy. Finally, our laboratory is highly active in drug discovery, pre-clinical screening, and early clinical translation of biologics (antibodies, cytokines, cell therapy) and small molecules for the treatment of leukemia. We have directly contributed to the development of 7 drugs now FDA approved for blood cancers (rituximab, alemtuzumab, azacitidine, idelilisib, ibrutinib, acalabrutinib, and tafasifamab). As a team, we value close collaboration with industry partners to bring forth impactful therapeutics and diagnostics that improve the lives of patients with leukemia and related blood diseases.
Energy Metabolism in Cancer:
To decode the cellular dynamics and energy metabolism altered in cancers for developing new therapeutics, the laboratory of Atsuo Sasaki, Ph.D. Add links to faculty profile and lab is investigating the cellular mechanisms that detect and control GTP levels, an energy source critical to support rapid cancer growth. His team identified PI5P4Kβ as the culprit, establishing it as the first GTP energy-sensing kinase ever discovered (Sumita et al., 2016, Mol Cell). Also, his team has discovered tumor-promoting reprogram of GTP metabolism in brain tumors and the other metastatic solid tumors (Kofuji et al., 2019, Nat Cell Biol). The team is now exploring potential therapeutic applications by targeting the GTP-metabolic reprogramming associated with cancers while continuing to investigate the molecular pathways that PI5P4Kβ uses to gauge and manipulate GTP levels.
Theragnostic Drug and Biomarker Discovery:
The laboratory of Xiaoyang Qi, PhD, focuses on cell membrane phosphatidylserine (PS) as a unique and specific target for cancer therapy and diagnosis. The lab has demonstrated: 1. cancer cell surface PS is critical for creating the TLR2/6-dependent immune-deficient environment that allows tumors to grow and metastasize and to induce drug- and radio-resistance; 2. tumor cells with higher surface PS are more sensitive to the cytotoxicity of various saposin C (SapC)-based lipid nanovesicles, especially SapC-DOPS (BXQ-350, Bexion Pharmaceuticals), a drug composed of the natural protein, SapC and dioleoylphosphatidylserine (DOPS), which is a PS-specific targeted and potent therapeutic agent in preclinical and clinical studies. This stable drug formulation was originally discovered and developed in Dr. Qi’s laboratory and multiple phase I clinical trials (NCT02859857, NCT04404569, NCT04771897, and NCT03967093) have recently been completed and opened showing a very strong safety profile.
Hemostasis Research Program:
Research in the laboratory of Vladimir Bogdanov, PhD, spans basic and translational cancer research, vascular pathobiology, and post-transcriptional regulation of gene expression. Currently, one area of focus comprises biological functions of Tissue Factor splice variants and the roles they play in the progression of solid malignancies and cancer-associated thrombotic disorders. Another area of focus comprises mechanistic contributions of erythrocytes to the propagation of systemic inflammation in diet-induced obesity – a pathological state associated with a risk of developing cardiovascular disorders, type 2 diabetes, and certain forms of cancer.
Prostate Cancer Biology:
The laboratory of Zhongyun Dong, MD, PhD, focuses on prostate cancer with the goal to further understand the molecular mechanisms underlying cancer development and progression and to develop novel therapies against this disease. The lab has shown that TGF-b-regulated IL8 expression contributes to tumor angiogenesis and cancer progression and that adenoviral vector-mediated intratumoral delivery of IFN-b, through inhibition of tumor angiogenesis, could be an effective therapy for advanced prostate cancer. The lab also identified several novel small molecule compounds targeting androgen receptor, microtubule, and proliferating cell nuclear antigen, and demonstrated the therapeutic effects of the compounds in mouse models of human prostate cancers.