Cancer Biology

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:
Dali Ma
300 Pasteur Drive
Alway Building, M-105
Stanford, CA 94305-5121
(650) 723-6198
(650) 725-3867 (fax)
dalima@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 L. Cleary. The role of onco-proteins in cancer and development. Molecular and cellular biology of lymphoid malignancies; role of lymphoid oncogenes in development.

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.

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.

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.

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.

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.

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.

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.

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.