Discovery and Developmental Therapeutics
Physician scientists and researchers in the DDT program identify key targets for effective personalized therapeutic intervention and to develop novel therapeutic approaches for detecting and treating cancer. Members have expertise in novel drug discovery, state-of-the-art cancer imaging, immunotherapy, genomics, epigenomics, bioinformatics, transplantation, and innovative clinical trials.
William Drobyski, MD
Professor of Medicine, Pediatrics, Microbiology & Immunology
MCW Eminent Scholar
- Program Leader, 2010
- Research focus, pathophysiology of GVHD
- Federally funded for over 20 years
1) Identify novel therapeutic targets and agents based on new knowledge of signaling pathways, metabolic programs, and tumor microenvironment relevant to cancer initiation, progression, and therapeutic resistance. DDT investigators continue to identify signaling cascades, metabolic pathways, and tumor microenvironment alterations in solid tumors for developing targeted therapeutics and important biomarkers/imaging modalities for diagnostic, prognosis as well as selection and response to therapy.
2) Discover new immunological agents that enhance the effectiveness of cancer therapy and strategies to suppress unwanted immune responses in bone marrow transplantation patients. Discover new immunotherapeutic agents that enhance the effectiveness of cancer therapy and strategies to suppress unwanted or off target immune responses in bone marrow transplantation patients. DDT members work to elucidate mechanisms of malignant hematopoiesis, to enhance understanding of the proinflammatory pathways that compromise the efficacy of allogeneic hematopoietic stem cell transplantation (HSCT), and to develop immune therapies for hematological malignancies.
3) Use advanced genomics, epigenomics, and bioinformatics to stratify tumor subtypes with the goal of gaining insight into novel therapeutic approaches. In collaboration with the newly form Genomics and Individualized Medicine Program, DDT members are rapidly embracing the disciplines of genomics, epigenomics, and bioinformatics to gain mechanistic insights underlying the development and malignant behavior of both hematological malignancies and solid tumors. More importantly, these efforts are identifying new therapeutic targets as well as new prognostic markers. Through these efforts, the development and use of genomics and epigenomics panels seeks to improve the personalized treatment of cancer subtypes. New drugs that target either mutated genomic pathways or altered epigenomic regulators are being tested either alone or in combination in preclinical trials with the goal of building the rationale to initiate clinical trials in the near future.
Selected NIH Funded Centers and Projects, DDT Program
Mary Horowitz, MD, MS
Center for International Blood and Marrow Transplant Research
The Center for International Blood and Marrow Transplant Research (CIBMTR) is the international leader, and only of its kind resource, in blood and marrow transplant research. Dr. Horowitz is the founder and leader of this collaboration of the National Marrow Donor Program/Be the Match and MCW. Her revolutionary and cooperative work with the global scientific community has advanced hematopoietic cell transplantation (HCT) and cellular therapy worldwide to increase survival and enrich quality of life for patients. The CIBMTR facilitates critical observational and interventional research through scientific and statistical expertise, a large network of transplant centers, and a unique and extensive clinical outcomes database. Research from CIBMTR investigators has been published in many high-impact journals including Nature and the New England Journal of Medicine. Several major policy and CMS coverage changes have resulted from data published by CIBMTR scientists, including securing Medicare coverage for HCT in patients over 65 years of age.
Ehab Atallah, MD and Kathryn Flynn, PhD (CPO Program)
Stopping Tyrosine Kinase Inhibitors in CML Patients (Stop-TKIs)
The current recommendation for chronic myeloid leukemia (CML) patients is to continue Tyrosine kinase inhibitors (TKIs) therapy indefinitely, despite high costs and significant side effects that decrease patients' health-related quality of life. This study discontinues TKI therapy in 170 willing and eligible CML patients and monitors them closely for 3 years in order to characterize:
- Factors associated with CML recurrence
- Patient-reported health status changes after TKI discontinuation
- Patient decision making regarding TKI discontinuation with monitoring
William Drobyski, MD
Cannabinoid-Mediated Mitigation of Graft Versus Host Disease: Roles of CB2 Receptors and Adenosine Signaling
Regulatory T Cell Populations in Graft versus Host Disease
Role of Interleukin 23 in Gastrointestinal Graft versus Host Disease
MCWCC is regionally and nationally known for the research-driven treatment of hematological cancers, including transplantation, and for research into the prevention and treatment of graft vs. host disease, which is the major side effect of transplant. The research-led transplantation program at the Froedtert and Medical College of Wisconsin Cancer Center is ranked a 1+ by the National Marrow Donor Program, meaning that transplant outcomes are well above the national average. Dr. Drobyski plays a major role in these excellent outcomes. A nationally renowned physician scientist who is an expert in graft vs. host disease, he has been NIH funded for over 20 years and continues to improve outcomes for those patients who develop graft vs. host disease after transplantation.
Adriano Marchese, PhD
GPCR Regulation of AKT Signaling
Mechanisms governing G protein-coupled receptor (GPCR) signaling play a critical role in many human diseases, including cancers. Dr. Marchese is working to characterize and explain the molecular mechanisms specific to chemokine receptor CXCR4, the GPCR over-expressed in many metastatic cancers. Understanding CXCR4 mechanisms can lead to new and innovative therapeutic targets to treat and prevent metastatic disease.
Bin Ren, MD, PhD
Epigenetic and Transcriptional Regulation of Angiogenic Regulator CD36 and Transformation of Capillaries into Small Arteries
Dr. Ren is working on this comprehensive evaluation of arteriolar differentiation and capillary arterialization. This work is among the first to illuminate several poorly explored and poorly understood aspects of vascular biology, including those critical in tumor growth and metastasis.
Vera Tarakanova, PhD
IRF-1: A Brake to Limit Gammaherpesvirus Infection and Pathogenesis
Continuing her groundbreaking work on the role of viruses in the development of cancer, in this project Dr. Tarakanova is specifically researching gammaherpesviruses, which infect a majority of adults and can lead to virus-driven B cell lymphomas. Preliminary studies identified a host transcription factor that is likely to oppose the formation of virus-driven lymphomas, and her current work revolves around determining how this host transcription factor opposes viral processes to restrict virus infection and, possibly, virus-driven cancer.