The Cancer Biology Program


Liaison: Martin Brown, Ph.D. Director

(415) 723-5881 Fax: (415) 723-7382

Introduction


Research on the basic biology of cancer has coalesced and solidified in recent years as investigators have discovered oncogenes and tumor suppressor genes, and studied their role in signal transduction and control of the cell cycle. A large interdisciplinary program, Cancer Biology includes forty faculty from nearly every department in the School of Medicine (including both basic and clinical departments) and the Department of Biological Sciences. Currently fifty-seven graduate students and eight postdoctoral students are members of the program. Our research covers a wide range of modern cellular and molecular biology. There is no specific focus on cancer per se, instead, the study of both normal and abnormal cellular processes is considered relevant to the cancer problem. The offerings for corporate members of Spectrum by this Program are listed below:

Attendance at annual Cancer Biology Retreat


Each year, all cancer biology students, both predoctoral and postdoctoral, attend a two-day retreat at the Asilomar Conference Center on the Monterey Peninsula. Each student gives a 15 minute presentation of his/her work, including discussion and questions. This retreat is also attended by many of the faculty preceptors of the students. In addition to the scientific talks, there are two socials and time for relaxation on the beach. This retreat provides a marvelous opportunity to hear the latest research underway in the laboratories of the Cancer Biology faculty, as well as to meet the students and their faculty mentors.

Spectrum members will receive:

Opportunity to lecture in and/or audit Cancer Biology Core Course


The Cancer Biology Program organizes a three-quarter, twice-weekly lecture course highlighting the molecular, cellular, and histological aspects of the cancer problem, from etiology to treatment. The lecturers in this course are chosen not only from Stanford faculty, but also from institutions throughout the United States for their world-class reputation in their field. Examples of topics covered in the core course are: · DNA damage and repair · Neoplastic transformation · Radiation and chemical carcinogenesis · Viruses and cancer · Radiotherapy and immunotherapy · Oncogenes and tumor suppressor genes · Gene therapy This overview course is given every two years. In alternate years, the department sponsors another three-quarter course that focuses in depth on three aspects of the cancer problem. Again, lectures are given by Stanford faculty and scientists from other institutions.

Spectrum members will receive:

"Molecular Biology for the Modern BusinessPERSON": A 1 1/2-hour teaching lecture.


A major impediment to understanding modern molecular biology by nonspecialists (including nonscientists and scientists not specifically trained in the techniques) is the field's often arcane terminology and techniques. This 90-minute lecture, given by the director of the Cancer Biology Program, is specifically for the nonspecialist. It deals with the terminology, techniques, and concepts of modern molecular biology. Its purpose is to increase the nonspecialist's understanding of modern biology and promote better communication between scientists and nonscientists.

Spectrum members will receive:

Recruitment possibilities from over 60 students.


Scientists who attend the annual retreat or the lecture course or the student-run Journal Club (see below) will be able to meet one-on-one with all of the graduate and postgraduate students. In addition, any job openings can be quickly brought to the attention of all students via e-mail from the Cancer Biology Program Office.

Spectrum members will receive:

Invitations to speak at student-run Journal Club


The Cancer Biology students organize a monthly Journal Club focusing on current literature. They also invite faculty speakers and/or members of local companies. Spectrum members will receive: An invitation for company scientists to attend and speak at the student-run Journal Club. Round Table workshops on selected topics The Cancer Biology faculty are pleased to hold informal round table workshops with corporate partners. Typically a small group of faculty-generally from one to four faculty members-will meet with corporate members to discuss areas of mutual interest. For example, round table topics might include: · Current work on oncogenes and tumor supressor genes. · New strategies of cancer treatment, including gene therapy. · New developments in metastasis research.

Spectrum members will receive:

Opportunities to organize an annual round table workshop with selected Cancer Biology faculty in an area of their interest.

Faculty



Abdul Matin, Associate Professor Department of Microbiology and Immunology

We are involved in molecular and physiological analysis of the biological stress response. We have identified several genes in E. coli that are expressed when bacteria are exposed to starvation. Information about these genes can be utilized to construct bacterial strains that are more resistant to stresses. Engineered bacteria may be able to maintain a high-level of productivity under conditions that hinder growth.

Helen Blau, Professor Department of Pharmacology

Our major focus is how cells become differentiated and remain so during development, and how differentiation goes awry in cancer. We are elucidating the molecular mechanisms that promote differentiation and have found that the differentiated state seems to require continuous molecular regulation. We are also analyzing the mechanisms underlying pattern formation in mammalian muscle and using myoblasts for gene therapy. We have shown that myogenic precursor cells can be isolated, engineered, reintroduced, and that they then will express recombinant proteins.

John Boothroyd, Associate Professor Department of Microbiology and Immunology

We are studying two parasitic protozoans, Trypanosoma brucei and Toxoplasma gondii, both of which are major pathogens. In T. brucei we are studying its antigenic variation and genetic regulation. In T. gondii we are investigating its ability to reproduce in almost any cell type, its genetics and possible vaccines for the microbe. Linda Boxer, Associate Professor Department of Hematology We are studying three types of cancer cells that each show deregulated expression of an oncogene, with the hope that we can discover and interfere with the mechanisms of deregulation. We are trying to determine the mechanisms of activation in c-myc in Burkitt's lymphoma, the regulation of c-myb and bcl-2 in hematologic malignancies.

J. Martin Brown, Professor Department of Radiation Oncology

Our goal is to understand the mechanisms responsible for the resistance of solid tumors to various cancer therapies and to develop strategies to overcome these resistances. We are now involved in developing drugs that kill hypoxic cells (which are usually resistant to other therapies), finding molecular predictors of tumor response to treatment, studying the radiosensitive scid mutation in mice, and studying genes that are activated by radiation.

Eugene Butcher, Associate Professor Department of Pathology

We study cell-cell adhesion in the immune system, especially in the context of interactions of white blood cells with the endothelial lining of the blood vessels. These interactions regulate immune responses by controlling leukocyte access to sites of immune action. We are exploring the importance of three adhesion molecules in a variety of disease states, including rheumatoid arthritis and lymphoid cancers.

Michele Calos, Associate Professor Department of Genetics

One goal of the lab is to discover what DNA sequences are necessary and sufficient for initiation of replication in eukaryotic cells. We have developed a unique modeling system to study this question. Another goal is to shed more light on how complex eukaryotic chromosomes work, by constructing artificial chromosomes from authentic chromosomal components, including centromeres and telomeres. Such artificial chromosomes may be attractive vectors for genetic engineering in eukaryotic organisms.

Christine Cartwright, Assistant Professor Department of Medicine

We are studying the mechanisms that regulate the oncogene c-src in intestinal epithelial cells. We are also purifying tyrosine kinase substrates from colon carcinoma cells; we plan to isolate the genes encoding the substrates and introduce mutations into major Tyr phosphorylation sites.

Michael Cleary, Associate Professor Department of Pathology

We are studying the pathogenetic role of various chromosomal aberrations in human malignancies. We have demonstrated that several of the proteins encoded by cellular oncogenes are transcription factors that fuse with cofactors. We are studying the effects and consequences of protein fusion on gene transcription and transformation. We are also concerned with devising new molecular diagnostic procedures for detecting and monitoring leukemia patients.

Gilbert Chu, Assistant Professor Department of Oncology

We are studying xeroderma pigmentosa (XP) patients for clues to how human cells recognize and repair damaged DNA. We have identified a factor that recognizes multiple forms of DNA damage and which is defective in XP group E. In a separate line of investigation, we have been studying the separation of very large DNA by pulsed-field electrophoresis. We are interested in designing new devices and applying the technology to long-range mapping of the human genome.

Carol Clayberger, Assistant Professor Department of Cardiothoracic Surgery

Our group is studying the molecular basis of class I MHC recognition, as well as investigating methods to interrupt recognition in animal models of transplantation. In addition, we are interested in the response of T cells to tumor-specific antigens presented by class I molecules, and in development of novel vaccines to treat certain types of B cell lymphomas.

Heinz Furthmayr, Professor Department of Pathology

Our group is interested in defining the role of novel cytoskeletal proteins in cell-matrix interaction, contact guidance and signal transfer. We have cloned and sequenced three closely related genes that code for a new class of cytoskeletal proteins. In addition, we are interested in defining mutations of genes involved in patients with Marfan Syndrome.

Amato Giaccia, Assistant Professor Department of Radiation Oncology

Investigating the relationship between genomic instability and DNA repair. Our results show that cell lines derived from tumors that are defective in DNA repair also show high levels of spontaneous chromosome rearrangements. We are also studying the initial signals that modulate the induction of certain cellular pathways in response to external stimuli, and the regulation of gene expression under low-oxygen conditions.

Linda Guidice, Associate Professor Department of Gynecology and Obstetrics

Our laboratory is examining insulin-like growth factors in the human uterus and ovary. We have discovered a series of IGF-binding protein proteases and we are exploring their role in leiomyosarcomata.

Harry Greenberg, Professor Department of Medicine

We are interested in pathogenic viruses that infect the GI tract and the liver. Some of the ongoing studies in our lab include: finding the rotavirus genes that code for host-range restriction and virulence, studying two rotavirus surface proteins, finding the mechanism for rotavirus neutralization and cell entry, and finding the regions of the hepatitis-C virus that are targets of neutralizing antibodies.

Andrew Hoffman, Associate Professor Department of Medicine

The laboratory is exploring the role of insulin-like growth factors (IGF) in the regulation of the central nervous system and the pituitary. We are also studying the role of growth hormone therapy in muscle growth and strength in the elderly, and evaluating the potential use of IGFs as anabolic agents.

Aaron J. W. Hsueh, Professor Department of Obstetrics and Gynecology

We are interested in the molecular and cell biology of the ovary, with special emphasis on hormonal action and gene expression. We have cloned the human genes for FSH and LH receptors and are developing in vitro bioassays to measure serum levels of FSH and LH. We are also using a mouse model to study the mechanisms of gonadal tumorigenesis.

Wray H. Huestis, Professor Department of Chemistry

My research concerns the molecular mechanisms whereby cells control their shape, motility, deformability, and the structural integrity of the their membranes. Our projects include studies of: the metabolic control of interprotein and protein-lipid interactions, the role of lipid metabolism and transport in regulating the fluid dynamics of cell suspensions and cell-cell, and cell-liposome interactions.

Patricia P. Jones, Professor Department of Biological Sciences

We are investigating the genetic, molecular, and cellular mechanisms by which MHC proteins affect immune regulation. In particular, our research focuses on how the extensive genetic polymorphism of MHC proteins affects immune responsiveness and disease susceptibility, and how the expression of MHC proteins is regulated.

Susan Knox, Assistant Professor Department of Radiation Oncology

Our group is developing a comprehensive radioimmunotherapy (RIT) program for the treatment of patients with lymphoma and solid tumors. We are also conducting a program to better understand RIT so that the therapy can be optimized.

I. Robert Lehman, Professor Department of Biochemistry

Our laboratory is involved in the analysis of DNA replication and recombination in eukaryotes. Our studies involve embryos of Drosophila melanogaster and mammalian cells infected with herpes simplex virus.

Ronald Levy, Professor Department of Medicine

Our research concentrates on the study of malignant lymphoma. We are using the tools of immunology and molecular biology to develop a better understanding of the initiation and progression of the malignant process. We are interested in cell-signaling important in cell growth, and in possible vaccines and other treatments that can be used against tumors.

Micheal Lieber, Assistant Professor Department of Pathology

Our studies focus on the regulation of three nuclear enzyme systems that conduct site-specific recombination and mutation at the antigen receptor genes. We are trying to define the protein components of V(D)J recombinase, which catalyzes the assembly of the variable-domain exon of the antigen receptor genes. We are also studying the site of the immunoglobulin class switch recombination and somatic hypermutation.

Anson Lowe, Assistant Professor Department of Medicine

We are interested in characterizing the determinants that target membrane proteins to the pancreas exocrine secretory granule, and learning the extent to which the secretory granule contributes to the biogenesis of epithelial polarity. We are also interested in diseases of the pancreas. Ongoing projects include the development of serum assays for pancreatic disease and the mechanisms underlying the pathogenesis of pancreatitis.

David McKay, Professor Department of Cell Biology

Our general area of interest is in structural and mechanistic studies of macromolecules. We are currently studying the structure and mechanisms of action of the 70 kilodalton heat-shock-related proteins, the regulatory molecules of the visual system, and catalytic RNA.

John Niederhuber, Chair Department of Surgery

I am trying to gain a clearer understanding of intracellular signal pathways, and of the molecular basis of lymphocyte activation, in order to determine the aberrant mechanisms involved in immunologic dysfunction and in the development of cancer. My research efforts over the last decade have been directed toward the development of implanted drug delivery systems and the generation of intra-arterial chemotherapy for liver tumors.

Garry Nolan, Assistant Professor Department of Pharmacology

The research in our laboratory focuses on signal transduction and gene regulation using the NF-KB/Rel and IKB/ankyrin families of transcriptional regulators.

Roeland Nusse, Associate Professor Department of Developmental Biology

Our lab is currently investigating the role of two oncogenes, Wnt-3 and Wnt-3A, in the development of the mouse central nervous system. We are also investigating the properties of the Wnt gene family in Drosophila.

Bishr Omary, Assistant Professor Department of Gastroenterology

Our research interest focuses on the function of intermediate filament (IF) proteins, the most complex and least understood of the cytoskeletal proteins. We are investigating the IF proteins that are found on single-layered "simple" epithelial cells, such as those in intestine, liver and pancreas.

Jane Parnes, Associate Professor Department of Medicine

Our laboratory studies the function and regulation of lymphocyte surface proteins, with a primary focus on the CD4 and CD8 cells. We are studying the proteins that regulate these cells during T-cell development and activation. A second area of study involves the B-cell protein CD72/Lyb-2, which disappears once a B cell differentiates into antibody-secreting plasma cells.

Frank E. Stockdale, Professor Department of Oncology

We focus on embryonic cell commitment and determination during the formation of cell lineages in vertebrate development. We are trying to discover: the cellular origin of the first skeletal muscle fibers in the embryo, the mechanism for isoform switching during embryonic development, and the functional and structural importance of myosin isoform expression in early skeletal muscle and cardiac muscle development.

Virginia Walbot, Professor Department of Biological Sciences

We recently cloned Mu9, the autonomous element of maize's most aggressive transposon, Mutator. We are analyzing the role of its two transcripts and the impact Mu transposon insertions have on gene expression.

Teresa S. F. Wang, Professor Department of Pathology

We are interested in the molecular mechanisms that regulate cell growth. We are studying the structure-function relationships of human DNA polymerase alpha and the control of DNA replication and cell division is yeast. We are also doing mutational studies of anti-HIV therapeutic drugs.

Charles Yanofsky, Professor Department of Biological Sciences

We are studying the mechanisms of gene regulation in E. coli, particularly the trp repressor, the trp operon, and the tryptophanase catabolic operon. We are also studying Neurospora crassa and the mechanisms of regulation of the gene encoding the global transcription regulator, CPC1.