City of Hope’s Department of Molecular and Cellular Biology, originally Molecular Genetics, was formed in 1982 under the direction of Keiichi Itakura, Ph.D., professor of molecular biology. Research interests in thedepartment include an array of biological systems and problems, but the unifying theme is mechanisms regulating expression of genetic information at both the transcriptional level (where DNA directs the synthesis of RNA) and the post-transcriptional level (meaning how genes control protein synthesis from newly-transcribed RNAs).
The department includes eight independent laboratories as well as theElectron Microscopy core facility, overseen by Marcia Miller, Ph.D. and Zhuo Li, Ph.D.
Investigators within the department actively collaborate with investigators in the medical center, making important contributions to clinical investigations at City of Hope. The faculty also collaborates with the wider academic and scientific community. Faculty members have served numerous leadership roles, including with the National Institutes of Health, American Cancer Society and the Army Breast Cancer Research Program.
Department faculty members also teach and mentor graduate students in City of Hope’sIrell & Manella Graduate School of Biological Sciences. The department offers students the opportunity to carry out research in genetics, developmental biology, molecular genetics, molecular biochemistry, cell biology, molecular virology, and molecular and cellular immunology.
John J. Rossi, Ph.D. - siRNA and ribozymes
The focus of this laboratory is the biology and therapeutic application of small RNAs, with particular emphasis on small interfering RNAs (siRNAs) and ribozymes as therapeutic agents for the treatment of HIV infection.
Adam Bailis, Ph.D. – Genetics and molecular biology
This laboratory uses genetic and molecular biological approaches to study how DNA replication and repair are coordinated in the maintenance of genome stability.
Mark Boldin, M.D., Ph.D. – Noncoding RNA control of mammalian hematopoiesis, immunity and cancer
Research in this lab is focused on the biology of noncoding RNA and the understanding of its role in the regulation of inflammation and cancer using molecular, biological and genetic approaches.
Keiichi Itakura, Ph.D. – Molecular biology
The laboratory of Keiichi Itakura, Ph.D.,studies the role of ARID transcription factors in the development and maturation of adipocytes and carcinogenesis. They also study molecular events in energy balance, as well as the functions of homeobox genes in prostate cancer.
Ren-Jang Lin, Ph.D.– RNA processing and regulatory RNA
The research objectives of this laboratory are two-fold, both centered on RNA: to decipher the molecular mechanism of RNA processing, and to reveal novel roles of RNA in regulating gene expression, with emphasis on aberrant cellular factors linked to human diseases.
Linda Malkas, Ph.D.– DNA replication/repair and human disease
The laboratory focuses on understanding the mechanisms mediating human cell DNA replication and repair and applying these discoveries to the development for new biomarkers and molecular targets for cancer.
Marcia Miller, Ph.D.– Molecular immunogenetics
Oncogenic herpesviruses disproportionately cause tumors in immunocompromised patients. This lab studies how genetic polymorphism influences the incidence of cancers caused by oncogenic herpesviruses.
Piroska Szabo, Ph.D.– Epigenetics
This laboratory investigates the epigenetic mechanisms governing genomic imprinting using methods of genetics, biochemistry and molecular biology. The group is also involved in environmental reproductive epigenetics.
Yeast genetics; post-transcriptional processing
The department maintains extensive expertise in yeast genetics and molecular biology. Studies focus on mechanisms involved in homologous recombination and post-transcriptional processing of premessenger RNAs. Research also includes the development and applications of RNA aptamers regulating diverse processes ranging from pre-mRNA splicing to receptor-mediated delivery of small interfering RNAs (siRNAs) to treat cancer and viral infections.
Defining the epigenetic mechanisms regulating gene expression is vital to understanding both normal development and carcinogenesis. Investigative efforts include determining mechanisms of genetic imprinting and the role of small RNAs in heterochromatin formation. Research on the function of small RNAs is an important program in the department. There is also strong emphasis on how microRNA functions as a post-transcriptional regulator of gene expression. Several laboratories are exploring therapeutic applications of RNA interference.
DNA replication/repair and human disease
Organisms need to safeguard genetic information to prevent the damaging effects of aging and disease. This is accomplished by accurate replication of DNA and by repair of any damage incurred as a result of endogenous or exogenous factors. New exciting details about DNA replication and repair are being discovered. These processes are proving to be highly interconnected, and could lead to treatments for various diseases and age-related disorders.
Biochemistry of DNA damage and repair
Understanding how DNA is damaged, both by mutagens and by treatments such as chemotherapy and radiotherapy, and the mechanisms governing DNA repair or the failure thereof, are essential to progress in developing better prevention and treatment strategies for a variety of cancers.
ARID transcription factors
This class of DNA-binding proteins plays multiple roles in the normal development of a variety of tissues, most prominently fat, bone and muscle. Recent discoveries suggest that these factors help to create activating "bookmarks" in genes that are crucial for establishing and maintaining the identities of these tissues. Therefore, the study of ARID transcription factors may lead to a greater understanding of medical problems ranging from obesity and diabetes to muscular injury, skeletal defects, and cancer.
Genetic influences in responses to cancer and infection
Investigations are underway to elucidate how and by what mechanisms genetic variability determines immune responses to virally-induced lymphomas.
Non-coding RNA control of mammalian hematopoiesis, immunity and cancer
Understanding the molecular mechanisms that govern immune cell development and function is key for the advance of novel therapeutic approaches to treat autoimmunity and cancer. Noncoding RNAs, in particular microRNAs, play a critical role in shaping the mammalian immune response and hematopoiesis, and are the focus of our research interest.
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