Institute for Stem Cell & Regenerative Medicine

at the University of Washington

Cancer Stem Cells

Janis Abkowitz (Hematology, Medicine)
Dr. Abkowitz studies the in vivo behavior of hematopoietic stem cells (HSC) in transplantation models and in parabiotic mice. She has shown that the divergent patterns of clonal contribution in individual animals following limiting dilution transplantation can be explained by the stochastic differentiation of HSC and has investigated the mechanism by which neoplastic HSC dominate in the myeloproliferative disorders. She also studies the pathogenesis and therapy of erythroid marrow failure and the role of heme export in this process.

Qinghua Feng (Pathology)
The main interest of the lab is to investigate epigenetic mechanism of carcinogenesis. Currently, we are focusing on two projects that are related to stem or progenitor cell biology. The first project involves circulating tumor cells (CTCs) and breast cancer biology. It is hypothesized that a small fraction of CTCs are tumor stem cells which have the ability to generate distant metastases. We have isolated and cultured CTCs from metastatic breast cancer patients, and are in the process to characterize markers expressed by these in vitro cultured CTCs to determine whether they express breast cancer stem cell markers through quantitative RT-PCR analysis. The second project involves hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC). HCV infection can induce tumor stem-cell like signature. We have shown that specific epigenetic changes, such as p16 methylation, are associated with HCV infection caused HCC, and the polycomb histone methyltransferase EZH2 is overexpressed in HCC tissues compared to uninfected normal liver tissues. We are testing the hypothesis that HCV infection downregulates p16 via epigenetic mechanism, alleviate senescence regulation, increase hepatic progenitor cells proliferation, which subsequently contribute to hepatocarcinogenesis.

Marshall Horwitz, MD, PhD (Pathology)
The Horwitz laboratory has a longstanding interest in genes and mechanisms leading to hematological malignancy. More recently, the lab has focused attention on using somatic mutations to infer cell lineage in order to better understand how stem cells contribute to development, tissue regeneration, and cancer.

André Lieber, MD, PhD (Medical Genetics, Pathology)
The main objective of research in Dr. Lieber's laboratory is to develop new approaches for cancer therapy.

Edward H. Lin, MD (Medical Oncology)
My major research focus has been on translational research on colon cancer stem cells. Our goal is to develop personalized treatment strategies that will minimize the evolution tumor to the current treatment.

Alvin Liu, PhD (Urology)
Normal organ development depends on intercellular communication via diffusible factors and cell contact, without which diseases like cancer may arise. There are over 200 identifiable cell types in our body, plus many more diseased ones. To understand cell biology we need to determine what genes are expressed (transcriptome) by each cell type, and how this expression is altered in disease states. We employ cell sorting to isolate various cell types, including a possible stem cell type, from the prostate, bladder and kidney for analysis. The resultant cell transcriptomes are superior to the more common ones generated from tissues. The sorted cells are also viable and different cell types can be recombined in culture to study the molecular mechanism by which stem cells are induced to become differentiated cells (and the cancer process). Our lab developed the cell sorting strategy for cells of solid tissues and reported the first transcriptomes of individual prostate cell types and a prostate cancer cell type found in primary tumors.

Larry Loeb (Pathology)
We have developed a new methodology to measure mutation frequency in any segment of DNA with unprecedented sensitivity. We can detect in DNA, one single base substitution amongst one billion correct nucleotides. We are desirous of measuring mutation frequency in stem cells and progeny.

Ray Monnat, PhD (Pathology and Genome Sciences)
Our research focuses on human RecQ helicase deficiency syndromes such as Werner syndrome; high resolution analyses of DNA replication dynamics; and the engineering of homing endonucleases for targeted gene modification or repair in human and other animal cells.

Nephi Stella, PhD (Pharmacology)
We are interested in the molecular mechanism controlling the growth and migration of brain tumor stem cells. We are currently testing the hypothesis that pharmacological activation of cannabinoid receptors, a subclass of G protein-coupled receptor, control the growth and migration of cancer stem cells resulting in astrocytomas grade IV (as known as glioblastomas).

Larry True (Pathology)
His group works with the Liu group on the project above as well as transcriptome and proteome mediated functional differences in normal and diseased prostate and bladder.

Scott Tykodi (FHCRC)
Our research group is interested in renal cell carcinoma as a target for T cell immunotherapy. We have identified several antigens that are expressed on RCC tumor cell lines and recognized by T cells in vitro. We are now developing techniques to identify renal cell carcinoma stem cells in the laboratory using a xenogeneic transplant model in immunodeficient mice that has been applied to other human tumor types. This system will provide us the means to evaluate antigen expression on renal cell carcinoma stem cells that may in turn suggest compelling targets for the development of clinical therapy studies.

Valera Vasioukhin (FHCRC)
Our laboratory studies the mechanisms and significance of cell polarity and cell adhesion in normal mammalian development and cancer.

Alejandro Wolf-Yadlin (Genome Sciences)
The main focus of our lab is on the application of systems biology to the study of cancer. We develop proteomics tools to study cellular signaling dynamics and topology. We then apply these tools in conjunction with gene expression, epigenetic and phenotypic analyses of cellular systems to understand molecular and behavioral characteristics of cancer primary cells and cancer stem cells. The ultimate goal of our researcStemh is to identify molecular signatures of cancer progression that can illuminate potential drug targets as well as be utilized as diagnostic tools for early cancer detection.

Ray Yeung (Surgery)
Our group focuses on the pathogenesis of a pediatric hamartoma syndrome known as tuberous sclerosis complex. This proliferative disorder affects multiple pluripotent progenitor cells of the central nervous system, heart and kidney. We believe that the underlying signaling pathways (mTOR and b-catenin) play a significant role in regulating cell growth, proliferation, and differentiation of these immature cells. We use a handful of in vitro and in vivo approaches to explore the mechanism of the TSC proteins and their role in cancer and aging.

 

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