Department of Molecular Genetics
The Department of Molecular Genetics, which includes the Section of Virology, was established in 1987 with the mission to build the programmatic and methodological infrastructure of molecular biology within the Research Institute and to stimulate research on the structure, regulation and mechanisms of activity of viral and cellular genes. Since then, the Department has developed into a strong academic union of nationally recognized experts representing a broad spectrum of disciplines. It maintains the spirit of collegiality and mutual support, has a solid technical infrastructure and is efficiently run by an experienced administrative team. Ongoing research programs cover the following areas.
Understanding the molecular mechanisms of stress-, cytokine-, and oncogene-mediated signal transduction remains a major area of research within the Department. George R. Stark's and Ganes C. Sen's laboratories have a long-standing interest in deciphering mechanisms by which interferon (IFN)-mediated signaling occur in mammalian cells via activation of various signal transducers, resulting in changes in gene expression. Stark's team, in addition, is working on understanding the mechanisms of activation of NFkB by various stresses and its effects on cellular growth regulation. Sen's laboratory is involved in determining functional characteristics of several IFN-induced proteins as well as signaling initiated by double-stranded RNA. In addition, pathways involved in viral apoptosis are being delineated. Another area of interest is the analysis of specific physiological roles of different isoforms of angiotensin -converting enzymes using engineered mouse strains that express the protein in tissue specific fashions. Dennis W. Stacey's laboratory is focused on the role of oncogene ras-mediated signaling and topoisomerase II expression in control of cell cycle and cell response to chemotherapeutic drugs. The group develops and applies unique experimental approaches to the analysis of the cell cycle allowing revision of established dogmas in this highly competitive field.
The laboratories of two staff members are involved in understanding most basic mechanisms of cellular RNA synthesis and processing. Donal S. Luse leads a team that studies transcription by RNA polymerase II with specific focus on promoter clearance and regulation of initial steps of transcript elongation. Richard A. Padgett primarily focuses his studies on the molecular mechanisms of RNA splicing, including the chemistry of this process, identification of cellular factors involved in control of RNA splicing and evolution of splicing machinery.
Kurt W. Runge continues work on the replication and maintenance of telomeres, the physical ends of eukaryotic chromosomes, using budding yeast as a model organism. Besides understanding telomere structure and function, his work provides insights into the mechanisms of cellular aging, and the control of malignant transformation and is evolving towards development of new cancer treatment approaches.
Kwaku T. Dayie is an expert in biomolecular NMR spectroscopy methods development and application to analysis of RNA-RNA and RNA-protein interactions. This work complements the Department's existing strengths in RNA synthesis/processing and signal transduction research.
Jocelyn A. McDonald uses a combination of modern genetics and molecular, developmental and cell biology to identify genes that regulate cell migration during development, in the model organism, Drosophila melanogaster.
The laboratory of Peter M. Chumakov conducts active research programs in the p53 tumor suppressor field. Chumakov, a pioneer of this area of molecular oncology, is pursuing a program of development of new anti-cancer p53-targeting pharmaceuticals based on unique cellular model systems. A series of small molecules active against cervical cancer has been recently isolated, forming a solid basis for new anticancer drug development. This group is also involved in identification and functional analysis of new members of the p53 signaling pathway as potential targets for anticancer treatment.
The major advance for the past decade in science is that human genome sequence become available to the public. Constant risk from inside, such as reactive oxygen species or outside, such as ultraviolet light, endangers the integrity of our genome. One very dangerous form of damage is breakage of the genome sequence (DNA double strand break). Hisashi Tanaka's research goal is to determine how cellular mechanism protects our genome from DNA double strand break and how failure of maintaining integrity of the genome leads to cancer using our very unique genome-wide approach.
The Section on Virology is comprised of investigators who specialize in and recognize the paramount importance of investigating the molecular and immunological bases of the infectious processes of human viruses. Understanding the fundamental basis of how viruses cause the disease process still remains a colossal challenge to virologists. The laboratory of Amiya K. Banerjee is involved in understanding the biosynthetic pathways underlying how the genetic material of pathogenic viruses, e.g., vesicular stomatitis virus and human parainfluenza viruses, is expressed and regulated during their invasion of host cells. The laboratory's primary goal is to understand the molecular basis of pathogenicity of these two viruses, with an eye to developing antivirals and vaccines to combat these deadly viruses.
In summary, the Department of Molecular Genetics combines basic and translational research covering a whole range of problems, from understanding the basics of cell regulation to development of clinically useful pharmaceuticals. Our productive laboratories, led by nationally recognized principal investigators, are taking a well-defined course towards strengthening disease-oriented translational research programs in collaboration with other divisions of the Cleveland Clinic.