Laboratory of Sinisa Dovat, MD, PhD
Sinisa Dovat, MD, PhD, Director of Translational Research for both the Four Diamonds Pediatric Oncology Research Center and the Pediatric Oncology Experimental Therapeutics Program, focuses on the following projects:
- Biology and Treatment of Leukemia – this project studies the mechanism by which Ikaros, a tumor suppressor gene, controls the growth of leukemia cells in order to design a new treatment for this disease.
- Molecular Mechanisms of Cellular Immortalization and Senescence – this project dissects epigenomic events that control cellular immortalization and senescence in order to design a new class of drugs that regulate this process.
- Accelerated Drug Discovery – this project uses functional genomics and system biology approaches to accelerate the discovery of new drugs and drug combinations for childhood cancer.
Dr. Dovat's research is patient-oriented and translational with an emphasis on understanding basic mechanisms of disease in order to integrate the latest research achievements into clinical practice.
In addition to the Four Diamonds Endowment, Dr. Dovat's research has been supported by the National Institute of Health, and Hyundai Hope on Wheels.
Laboratory of Wei Li, PhD
The laboratory of Wei Li, PhD, is studying intercellular interactions during tissue homeostasis and determining how de-regulated interactions among cells promote cell transformation and tumor progression.
The goal of his research is to find molecular targets and biomarkers for cancer therapy. His laboratory integrates molecular, cellular and biochemical approaches in combination with mouse tumorigenesis models.
Currently, one of his major focuses is elucidating the regulation and function of the Hippo tumor suppressor pathway in brain tumors. He also uses in vitro and in vivo models to dissect biological interactions between heterogeneous malignant cells, and to study functional consequences of intra-tumor heterogeneity. He is also using functional screens, including genetic screens and small molecular screens, to search for oncogenic genes, which can promote brain tumor growth.
Dr. Li’s research is supported by National Institutes of Health (NIH), American Association for Cancer Research, American Cancer Society, and Pediatric Cancer Research Foundation.
Laboratory of Barbara A. Miller, MD
The laboratory of Barbara A. Miller, MD, Chief of the Division of Pediatric Hematology/Oncology, focuses on the role of ion channels in cell proliferation and differentiation and in regulation of bioenergetics.
Dr. Miller's laboratory is studying the function of members of the TRP superfamily of cation channels in malignant cell proliferation in leukemia and neuroblastoma. Members of this channel family have aberrant expression, usually high, in many cancers and may contribute to development of the malignant phenotype as well as chemotherapy resistance. One of these channels, TRPM2, has an important role in cell survival in oxidative stress and modulates mitochondrial function and bioenergetics. Because these channels are located on the cell surface, they have tremendous potential as future targets for drug therapy.
In work funded by the National Institutes of Health (NIH), Hyundai Hope on Wheels, and St. Baldrick’s, her laboratory is exploring the role of these channels in malignant cell growth and as novel therapeutic targets.
Laboratory of Vladimir Spiegelman, M.D., PhD
The laboratory of Vladimir Spiegelman, MD, PhD, is focused on the understanding of molecular pathways and environmental factors that lead to development of human malignancies, and employment of newly acquired knowledge for eradication of cancer.
This research focuses on the mechanisms that govern the turnover of short-lived mRNAs that encode important regulators of cell proliferation, death and differentiation and the implications of this turnover for tumor development. The mechanisms regulating mRNA degradation, its alterations in human cancers and its potential ability of therapeutic modality are of primary interest.
In the series of recent manuscripts published in Nature (2006), and Oncogene (2008), Molecular Cell (2009), Cancer Research (2009), Genes and Cancer (2010), Journal of Cell Science (2012), J. Biol. Chem. (2015) and others, Dr. Spiegelman’s group established the role and mechanism of RNA-binding protein CRD-BP in the regulation of expression of several important regulators of tumorigenesis including ßTrCP1, c-myc, Gli1, and MITF. CRD-BP is a novel transcriptional target gene of Wnt/ß-catenin/Tcf and c-myc. CRD-BP protein is essential for induction of mRNA of ßTrCP1, c-myc, Gli1, and MITF by ß-catenin signaling in several human cancers. Furthermore, high levels of CRD-BP that are found in primary tumors exhibiting active ß-catenin/Tcf signaling implicates CRD-BP induction in up-regulation of ßTrCP1, activation of NF-¿B suppression of apoptosis and resistance to chemotherapeutic agents in these diseases. Dr Spiegelman’s lab continues to analyze the role that CRD-BP plays in the pathogenesis of variety of malignancies using in vitro and in vivo models, aims to identify novel mRNA targets of CRD-BP that are important for tumor progression, and look for the potential therapeutic ways of inhibiting the function of CRD-BP.
The laboratory of Hong-Gang Wang, PhD, aims to better understand the fundamental mechanisms that control apoptosis (a cell self-killing mechanism) and autophagy (a cell self-eating process) in the context of oncogenesis. In addition, targeting of these two closely related, but distinct self-destructive processes for anticancer drug discovery and development is another major interest of his research group.
The ultimate goal of Dr. Wang’s research is to translate basic science discoveries to the development of new approaches for the treatment and prevention of childhood cancer. This laboratory is funded by the National Institutes of Health, Hyundai Hope on Wheels, Four Diamonds, and Lois High Berstler and provides an excellent training environment for students and fellows who are interested in basic and translational cancer research.