City of Hope Division of Biology

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Biology

The Division of Biology, one of the first basic science divisions established at the Beckman Research Institute, focuses on understanding the basic biological processes of genetics, gene expression and function, epigenetic mechanisms and DNA repair systems. Aided by the resources of the parent Department of Cancer Biology, and with a strong foundation in basic research methodology, division scientists are working to bring to light new insights that one day could produce novel therapies for a wide range of genetic diseases.

Independent investigators within the division study subjects ranging from molecular mechanisms of cancer to DNA repair and chromatin structure. At present, there are two major areas of investigation in the Division of Biology.

One active area of research in the division is the study of DNA damage, DNA repair and mutagenesis, which researchers use to assess links to the molecular epidemiology of cancer and therapeutic implications of those aspects. Gerd P. Pfeifer, Ph.D., Lester M. and Irene C. Finkelstein Chair in Biology, and Timothy R. O’Connor, Ph.D., each study DNA damage and repair mechanisms elicited by different chemical and physical carcinogens and drugs targeting DNA.

A second dynamic research area in the division focuses on epigenetics, or the study of heritable differences that do not depend on changes in primary nucleotide sequence. Epigenetics is an exciting, developing area of mammalian genetics research. Recently, researchers firmly established that epigenetic mechanisms are essential for normal mammalian development and play a role in several human genetic diseases and in cancer progression. Judith Singer-Sam, Ph.D., investigates allelic exclusion in the mouse nervous system, a phenomenon that results in expression from only one of the two alleles of a gene in a cell, although both alleles may be normal and have the same nucleotide sequence. Wen Yong Chen, Ph.D., is studying how epigenetic regulation controls mammalian longevity and cancer development. Arthur Riggs, Ph.D., studies DNA methylation and X chromosome inactivation, which involves the epigenetic silencing of all genes on one of the two X chromosomes in mammalian cells. Dr. Pfeifer also investigates mechanisms of epigenetic changes in cancer. Dustin E Schones, Ph.D., is investigating the role of chromatin organization in gene regulation and how this contributes to development and disease progression.

Additional studies delve further into the molecular origins of disease and maintain a clear focus on revealing the underpinnings of cancer and other life-threatening illnesses as well as potential pathways to new therapies.

Laboratory Research

Judith Singer-Sam, Ph.D. – Monoallelic Expression in the Central Nervous System
This laboratory has been using state-of-the-art screening techniques to identify genes that are expressed from only one allele in the central nervous system. A major focus is to further characterize a subset of candidate genes linked to human diseases including CNS developmental disorders. Understanding how these genes are regulated is relevant to the field of cancer epigenetics.

Wen Yong Chen, Ph.D. – Epigenetics, Cancer and Aging
The laboratory explores how a family of mammalian histone and protein deacetylases, sirtuins, are involved in regulation of aging and cancer development. These proteins can lead to novel approaches to address aging and to develop anticancer therapies.

Timothy R. O’Connor, Ph.D. – DNA Repair
The laboratory investigates DNA repair mechanisms to understand the protection of the genome from DNA damage and the origins of mutations leading to cancer. The research addresses how DNA damage is eliminated by DNA repair proteins and their accessory proteins, carcinogenesis, and exploiting DNA repair proteins as therapeutic targets. Interests in this area include the development of new models for carcinogenesis and the role of DNA repair in genomic stability of different cell types including those in the embryonic state.

Gerd P. Pfeifer, Ph.D. – Epigenetics and Genetics of Cancer
The laboratory explores genetic and epigenetic alterations in cancer and how they contribute to the origin of cancer cells. A major interest has been on defining basic molecular pathways that promote the formation of lung cancer by cigarette smoke components and skin cancer by sunlight ultraviolet radiation. The tumor suppressor RASSF1A was discovered in this laboratory and functional studies are underway to determine its molecular role.

Arthur D. Riggs, Ph.D. – DNA Methylation; X-Chromosome Inactivation
The laboratory studies gene regulation and mammalian development, X-chromosome inactivation, DNA methylation and epigenetic mechanisms. These mechanisms affect normal development as well as cancer development.

Dustin E. Schones, Ph.D. – Computational Biology and Genomics
This laboratory develops and applies computational methods with the overarching goal of understanding the complex architecture of gene regulation in development and disease progression. There is a current focus on utilizing genomic and epigenomic approaches to investigate how chromatin states interact with other regulatory elements to influence gene regulation.

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Beckman Research Institute

Recognized nationwide for its innovative biomedical research, City of Hope's Beckman Research Institute is home to some of the most tenacious and creative minds in science.