Targeted genome engineering technologies have emerged as a genetic tool for biological research and as a new class of therapies in biomedicine. Using the RNA-guided CRISPR/Cas9 system, zinc-finger nucleases (ZFNs), or TAL effector nucleases (TALENs), several labs are using genome engineering to study the functions of protein-coding and noncoding genes and to develop novel therapeutics for genetic and acquired diseases.
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
One project focuses on genetic influences in the incidence of Marek’s T-cell lymphoma. Another is centered on chicken MR1 polymorphism and microbiota that may cause disease in humans.
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.