Cancer Biology
Contact Information
Faculty and their Research Interests
Established in 1978, the Cancer Biology Program at Stanford University is an interdisciplinary program leading to the Ph.D. degree. During the past 30 years, our understanding of cancer has increased dramatically with the discovery of oncogenes, tumor suppressor genes, pathways of DNA damage and repair, cell cycle regulation, angiogenesis and responses to hypoxia, and recent glimpses into the molecular basis of metastasis and cancer stem cells. In addition, methods of parallel analysis including gene expression arrays, protein arrays, and tissue arrays have begun to refine and redefine the taxonomy of cancer diagnosis. This explosion of basic and clinical science has in turn resulted in the first successful cancer chemotherapies and immunotherapies based on a knowledge of specific molecular targets. With the newly established NCI designated Cancer Center, Stanford presents an excellent environment to pursue interdisciplinary cancer research.
The goal of the Cancer Biology Ph.D. Program is to provide our students with education and training that will enable them to make significant contributions to this remarkable field. Coursework during the first year is designed to provide a broad understanding of the molecular, genetic, cell biological, and pathobiological aspects of cancer. Students also learn about the current state of clinical diagnosis and treatment of human cancers. Each student is required to conduct a series of three laboratory rotations in the first year. By the beginning of the second year, each student will have chosen his/her research advisor and will have begun work on his/her dissertation project. A qualifying examination must be completed by the end of the second year. An annual Cancer Biology Conference at Asilomar on the Pacific Ocean provides our students with an opportunity to present their research to one another and to the faculty. The expected time to degree is four to five years.
For more information contact:
Grace Kolar
Cancer Biology Program Administrator
269 Campus Drive
CCSR 4325A
Stanford, CA 94305-5173
(650) 723-6198
(650) 721-1905 (fax)
gracebk@stanford.edu
http://www.stanford.edu/group/cancerbio
Faculty and their Research Interests
Steven Artandi. Cellular and genetic responses to telomere dysfunction and the biochemical role of telomerase, with the goal of better understanding human breast cancer.
Laura Attardi. p53-mediated apoptosis and tumor suppression, using biochemical, cell biological, and mouse genetic approaches.
Jeffrey D. Axelrod. Genetic and cell biological analyses of signals controlling cell polarity. Frizzled signaling and cytoskeletal organization.
Helen M. Blau. Stem cell biology. Cancer stem cells. Microenvironmental control of cell proliferation rates. Human lymphoma. Embryonic stem cells. Adult stem cells including muscle, blood and pancreas. In vivo imaging. Bioengineered cellular microenvironments. Nuclear reprogramming.
Matthew Bogyo. Functional studies of protease networks using chemical tools; design and synthesis of small molecules probes of proteases; dissection of proteases pathways involved in host cell invasion by the human parasites, Plasmodium falciprum and Toxoplasma gondii; imaging of protease activity during tumorigenesis.
Martin Brown. Yeast genomic approaches to understand gene function, drug mechanism of action and identification of new cancer susceptibility genes. In addition we use human tumor cells in vitro and as xenografts to develop new small molecule anticancer drugs that exploit the unique hypoxia of solid cancers.
Anne Brunet. Molecular mechanisms of aging and age-related diseases.
Bill Burkholder. We focus on identifying and characterizing signal transduction pathways used by the bacterium Bacillus subtilis to regulate cell cycle progression and development in response to chromosome status. Our goal is to understand the mechanisms of these pathways and how they contribute to normal growth, development, and genome stability.
Michele P. Calos. Development of novel vectors and strategies for gene therapy. Both extrachromosomal vectors and vectors that integrate in a site-specific manner are being developed.
Christine A. Cartwright. Molecular mechanisms of oncogene activation in colon cancer.
Chingpin Chang. We focus on understanding the mechanisms of cardiovascular development, particularly how the interactions among the major types of cardiac cells and neural crest cells generate heart tissues. We study the transcriptional and signaling events that coordinate such interactions and assembly into heart tissues.
Howard Y. Chang. Genomic studies of a wound response program in human cancers. Mechanisms of stromal cell specialization in normal and disease states.
James Chen. Understanding embryonic development and oncogenesis at the molecular level, including biochemical events within the Hedgehog and Wnt pathways. Chemical approaches to the study of embryonic patterning.
Gilbert Chu. Recognition and response to DNA damage; role of proteins in biochemical pathways for DNA repair.
Katrin F. Chua. Mammalian Sir2 proteins in cancer and aging; cellular senescence responses to genotoxic stress; chromatin regulation of genomic instability.
Karlene A. Cimprich. DNA damage-induced cell cycle checkpoints and the processes that contribute to maintenance of genomic stability.
Michael Clarke. Dr. Michael F. Clarke is the Associate Director of the Stanford Institute for Stem Cell and Regenerative Medicine. In addition to his clinical duties in the division of Oncology, Dr. Clarke maintains a laboratory focused on two areas of research: i) the control of self-renewal of normal stem cells and their malignant counterparts; and ii) the identification and characterization of cancer stem cells. A central issue in stem cell biology is to understand the mechanisms that regulate self-renewal of hematopoietic stem cells, which are required for hematopoiesis to persist for the lifetime of the animal. Until recently, the molecular mechanisms that regulate adult stem cell self-renewal were not known. His laboratory recently found that the proto-oncogene Bmi-1 regulates stem cell self-renewal via an epigenetic mechanism. By investigating the pathways upstream and downstream of Bmi1, the laboratory is actively investigating the molecular pathways that regulate self-renewal.
Michael L. Cleary. The role of onco-proteins in cancer and development. Molecular and cellular biology of lymphoid malignancies; role of lymphoid oncogenes in development.
Jennifer Cochran. The Cochran laboratory uses interdisciplinary approaches in chemistry, engineering, and biophysics to study complex biological systems. Our main goals are to develop new technologies for basic science and biomedical applications. Clinical applications of our research involve bone and wound healing, biomimetic corneas, neural cell regeneration, and cancer imaging and therapy. Our research is driven by the philosophy that in order to control physiological processes it is necessary to understand the molecular mechanisms that drive these processes. We are interested in elucidating molecular details of receptor-mediated cell signaling events; at the same time developing protein and polymer-based tools that will allow us to manipulate cellular processes on a molecular level. For biomedical applications, we are combining rational design and combinatorial methods to create designer protein therapeutics and diagnostic agents. One such example is highlighted in a recent press release:
http://news-service.stanford.edu/news/2006/may24/cochran-052406.html.
Stanley N. Cohen. Regulation of gene expression in prokaryotes and eukaryotes; cell cycle studies; RNA decay; plasmid biology.
Marco Conti. Cyclic nucleotide signaling and regulation of the meiotic cell cycle; kinases, phosphodiesterases, and phosphatases involved in the regulation of G2/M transition.
Gerald R. Crabtree. Regulation in cell proliferation and differentiation. Genetic regulatory mechanisms in T-lymphocyte activation; lymphoid development.
Martha S. Cyert. Mechanisms of Ca2+ dependent signal transduction and role of the conserved protein phosphatase, calcineurin. Genetic, genomic, biochemical and cell biological are applied to study the response of yeast to environmental stress.
Nicholas Denko. Tumor biology, especially the effects of the tumor microenvironment (such as hypoxia), hypoxic gene regulation, hypoxia effector genes, apoptosis.
Guo Wei Fang. Ubiquitin-dependent proteolysis controls intracellular protein abundance and serves a central regulatory function in many biological and pathological processes, such as cell cycle control, signal transduction, transcriptional regulation, protein trafficking, apoptosis, development, immune response, neuro-degeneration and tumorigenesis.
Dean Felsher. How oncogenes induce and sustain tumorigenesis, in particular how MYC proto-oncogene can contribute to tumorigenesis by causing genomic destabilization.
James Ferrell, Jr. Regulation of entry into and progression through mitosis and meiosis; understanding the basic logic of signaling cascades and loops.
Andrew Z. Fire. Cellular responses to foreign nucleic acids; RNA interference; roles of RNA-guided gene silencing in normal development and in disease.
James M. Ford. Mammalian DNA repair and DNA damage inducible responses; p53 tumor suppressor gene; transcription in nucleotide excision repair and mutagenesis; genetic determinants of cancer cell sensitivity to DNA damage.
Judith Frydman. Mechanism of protein folding and protein degradation in eukaryotic cells. Mechanism and function of molecular chaperones. Role of folding defects in cancer and other diseases.
Amato J. Giaccia. Cellular response to hypoxia and ionizing radiation; cell-cycle control, apoptosis and angiogenesis in transformed cells.
Or Gozani. Chromatin modification and cancer; Molecular mechanisms of signaling at chromatin during DNA damage responses; ING proteins in tumor suppression and apoptosis.
Isabella Graef. We study neuronal development and function using a combination of genetic, cell biological, biochemical, and chemical approaches. The two main foci of our lab are: (1) the interface of signaling and gene regulation in neuronal development, specifically calcineurin-NFAT signaling; and (2) the development of small molecules to modulate protein-protein interactions.
Ted Grave. I am is interested in applications of emerging functional and molecular imaging techniques in radiation therapy of cancer. In order to integrate these novel imaging procedures with state-of-the-art radiation therapy, a number of issues must be addressed. First, what are the molecular targets that hold the most promise for targeting and monitoring response to radiation therapy, and how can they best be visualized in vivo? Second, what are the limitations of novel imaging techniques that may bear on their application in radiation oncology? Third, how can one display, analyze, and segment multiple three-dimensional datasets to generate target volumes for radiotherapy? And finally, how will the information contained in imaging results of different modalities be integrated into the selection of a treatment course for a patient and subsequently, where appropriate, the specification of an optimized radiation target? These questions comprise my research. Projects that address these topics include the implementation and evaluation of clinical PET/CT imaging for radiation treatment planning, development and validation of novel PET tracers for preclinical and clinical imaging of tumor radiosensitivity and radiation response, development of software for multimodal image analysis, and study of tumor hypoxia and radioresistance in small animal models using a multimodality molecular imaging approach.
Samira Guccione. The focus of our laboratory is translational research leading to agents for clinical use in detection, diagnosis, treatment, monitoring, and prognosis of clinical pathologies. We use high-throughput genomic and proteomic analysis on clinical tissue samples to identify molecular targets of cancer. We have developed multimodality probes for MRI, gamma, fluorescence, and CT imaging. We are designing therapeutic approaches including delivery of targeted chemotherapeutic or radioactive agents or of non-viral-based genes for gene therapy.
Andrew Hoffman. The laboratory is interested in examining the role of insulin-like growth factors (IGF) in normal physiology and in oncogenesis. We are studying the molecular biology and physiology of IGF with an emphasis on the following areas:
1) We have shown that the IGF2 gene is parentally imprinted in most normal tissues, but that in some malignant neoplasms, the gene is biallelically expressed. Our inital work has concentrated on IGF2 gene expression in normal and neoplastic liver, kidney, uterine and breast tissues, where we have shown that the gene is overexpressed. Moreover, in nearly half of these tumors, IGF2 genomic imprinting is relaxed, leading to biallelic expression of the autocrine growth factor.
2) During our investigation of the mechanism for IGF2 imprinting, we have discovered that the imprinting process is promoter-specific, i.e., transcripts derived from promoters P2-P4 are imprinted while transcripts from promoter P1 are not imprinted. We are actively investigating the role of DNA and histone methylation in genomic imprinting.
3) Our group has actively studied the role of GH and IGF-I on body composition and exercise tolerance. We now plan to investigate the efficacy and safety of testosterone replacement in elderly men.
Paul A. Khavari. Epithelial growth, differentiation and cancer: studies of the genetic regulatory mechanisms controlling these process and development of new molecular therapies for cancer.
Susan J. Knox. Bcl-2, apoptotic signaling pathways (membrane and mitochondrial-mediated events), development of novel therapeutic strategies to sensitize tumor cells to cytotoxic therapies.
Albert Koong. My laboratory focuses on understanding hypoxia regulated signaling pathways and their relevance to pancreatic cancer.
Calvin Jay Kuo. Anti-angiogenic gene therapy, mechanisms of arterial endothelial specification, characterization of a novel mitogen encoded trimerized collagen XVIII endostatin domain.
Quynh Le. We focus on the identification of novel secreted-protein markers for hypoxia and prognosis in head and neck cancers. We aim to understand the role of osteopontin (OPN) in tumor progression in head and neck squamous-cell carcinoma (HNSCC); we investigate the effect of OPN on tumor-cell growth and metastasis in HNSCC; and we explore the possibility of using anti-OPN antibodies as a novel anticancer therapy. We also aim to understand how Galectin-1, a newly discovered hypoxia-regulated gene, serves as a link between tumor hypoxia and the modulation of tumor immune privilege.
Ronald Levy. Immunology and molecular biology of lymphoid malignancy; molecular vaccines for cancer.
Joseph S. Lipsick. Cell cycle regulation in vertebrates and Drosophila; molecular mechanisms regulating normal and malignant hematopoiesis; transcriptional regulation and cancer; evolutionary studies of the myb oncogene.
Anson W. Lowe. Regulated secretion and epithelial polarity in exocrine pancreatic cells; cellular precursors of pancreatic cancer.
M. Peter Marinkovich. Our lab is focused on studying how interactions among a number of basement-membrane-associated molecules drive tumorigenesis through activation of PI3-kinase, GTPases, and other signaling pathways. In turn, we are studying how these extracellular-derived signals are promoting changes in cell polarity, matrix deposition, proteinase expression, tumor invasion, and protection from cell death. Many of these interactions are proving amenable to antibody-mediated tumor inhibition and hold promise as future cancer therapies.
Ravindra Majeti. Dr. Majeti is a newly appointed Assistant Professor in the Department of Internal Medicine, Division of Hematology, and Institute for Stem Cell Biology and Regenerative Medicine at Stanford University. He was an undergraduate at Harvard, earned his MD and PhD from UCSF, and trained in Internal Medicine at Brigham and Women’s Hospital. Dr. Majeti completed his Hematology Fellowship at Stanford University and is a practicing board-certified hematologist. While at Stanford, he completed post-doctoral training in the laboratory of Irving Weissman, where he investigated early human hematopoietic stem cell development and characterized human acute myeloid leukemia (AML) stem cells. Dr. Majeti’s research is focused on investigation of the pathogenesis of human AML stem cells, as well as the targeting of such leukemia stem cells with therapeutic monoclonal antibodies. Dr. Majeti is a recipient of the Burroughs Wellcome Fund Career Award for Medical Scientists.
Beverly Mitchell. Our lab focuses on the development of new therapies for hematologic malignancies. We have long been interested in inosine monophosphate dehydrogenase (IMPDH) as a therapeutic target and have studied extensively the regulation of this enzyme and the potential role of inhibitors in the treatment of leukemia in preclinical and clinical investigations. We are also interested in the role of the protein Pso4 in DNA repair and in nucleolar proteins as possible targets for cancer treatment.
W. James Nelson. Mechanisms involved in the establishment and maintenance of epithelial cell polarity particularly E-cadherin. Organization and function of the spectrin-membrane skeleton associated with the Golgi complex.
Roeland Nusse. Role of the Wnt gene family in intercellular signaling during embryogenesis and tumorigenesis. We work on two Drosophila Wnt genes: wingless and DWnt-2.
Anthony E. Oro. Role of Sonic hedgehog (Shh) signaling system in the pathogenesis of basal cell carcinoma (BCCs) of the skin.
Donna Peehl. Prostate cancer and benign prostatic hyperplasia (BPH) are major medical problems. We have developed techniques with which we can establish primary cultures of epithelial or stromal cells from normal, BPH or malignant prostatic tissues. We have used these cultures to investigate many aspects of molecular and cellular biology of the prostate. Our overall goal is to characterize growth regulatory processes that occur in the normal prostate, then to identify aberrations that may occur in cancer or BPH. With this knowledge, we may develop new approaches for prevention,diagnosis or therapy of prostate cancer or BPH. One growth-regulatory factor of current interest in our laboratory is vitamin D. Our studies with prostatic cell cultures have shown that prostate cells have vitamin D receptors and are targets of growth-inhibitory and differentiating activities of vitamin D. Our pre-clinical studies have led to pilot clinical studies to explore the efficacy of vitamin D as a therapeutic agent against prostate cancer. Techniques used in our laboratory include cell culture of primary tissues in serum-free medium, three-dimensional cultures, tissue slice cultures, immunochemistry, immunoblots, and transfection.
Jonathan R. Pollack. Cancer genomics; microarray comparative genomic hybridization and expression profiling studies of cancer; genomic instability; novel cancer genes and diagnostic markers
Marlene Rabinovitch. Regulation of genes associated both with tumor cell proliferation and metastasis and with cardiovascular disease. How alterations in matrix-cell interactions, mRNA translation, and co-dependence of receptor signaling pathways cause malignant behavior of cancer and vascular cells.
Thomas Rando.
Associate Professor, Neurology & Neurological Sciences: Member, Bio-X
Our laboratory studies the basic molecular mechanisms of muscle stem cell activation, the effects of aging on skeletal muscle, and gene therapy for hereditary muscle diseases.
Jianghong Rao. We are interested in developing novel molecular probes for specific tumor imaging and cancer diagnostics. Our current focuses are to 1) synthesize nanoparticle-based biosensors, and 2) engineer trans-splicing ribozymes for tumor targeting and imaging.
Glenn D. Rosen. Characterization of apoptotic and growth stimulatory pathways in tumor cells. Regulation of the jun kinase pathway in tumor cells.
Julien Sage. Cell cycle control and tumor suppression mediated by Rb family members using cell biological and mouse genetic approaches.
Matthew Scott. Genetic regulation of animal development and human disease. We use mice and flies to study Hedgehog/Patched signaling and its links to brain cancer, development of the neural tube and cerebellum, planar cell polarity genes, a neurodegenerative disease called Niemann-Pick syndrome that affects intracellular organelle movements, chromatin proteins in embryonic stem cells, and genetic control of body size.
Tim Stearns. We study the organization and regulation of the microtubule cytoskeleton, and the relationship between the cell cycle and the cytoskeleton.
Zijie Sun. The role of nuclear hormone receptors in human malignancy.
Alejandro Sweet-Cordero. Our laboratory is devoted to the analysis of pathways involved in the initiation, progression, and maintenance of cancer. Utilizing both human and mouse model systems, we study aberrant oncogenic signaling, the role of the tumor microenvironment, and the mechanisms involved in chemotherapy response and resistance at the molecular, cellular, and organismal levels. We use functional-genomic approaches to identify genes that are relevant to cancer pathogenesis and treatment. Currently, our research focuses on the biology of sarcomas as well as on lung cancer pathogenesis and treatment.
Virginia Walbot. Developmental regulation of Mutator transposons and the development of anthers in maize.
Teresa Wang. Biochemistry and genetics of genomic instability induced by aberrant DNA replication and cell cycle checkpoint defects.
William Weis. Molecular basis of cell adhesion, Wnt signaling, and intracellular vesicle trafficking.
Irving L. Weissman. Development of T and B lymphocytes; cell-surface receptors for oncornaviruses in leukemia. Hematopoietic stem cells; lymphocyte homing, lymphoma invasiveness and metastasis.
Marius Wernig. Assistant Professor, Pathology - Stem Cell Institute. Epigenetic Reprogramming, Pluripotent Stem Cells, Neural Differentiation: implications in development and regenerative medicine.
Albert Wong. The goal of our laboratory is to define targets for cancer therapeutics by identifying alterations in signal-transduction proteins. Our lab first identified a spontaneously occurring mutant epidermal-growth-factor receptor (EGFRvIII) in glioblastoma. Basic studies on the signal-transduction pathways initiated by EGFRvIII have uncovered two other critical targets, the c-Jun N-terminal kinase (JNK) and Gab1. Our translational work has created diagnostic tools for EGFRvIII and a vaccine therapy currently in Phase II clinical trials.