Major Research Initiatives
Biochemistry and molecular biology is the study of the genetic and biochemical bases of cellular processes.
The faculty of the BMB department conduct research to gain new insights into the cellular and molecular mechanisms underlying normal and abnormal cellular processes, and their relevance as targets for improving health and treating disease.
Key areas of interest in the department include the study of pathways and mechanisms involved in the maintenance of genome integrity and protein homeostasis, in the response to various stresses, in reproductive and germ stem cell biology, and in aging. The biological settings in which we characterize these processes include normal physiology, bacterial and parasitic infection, cancer, neurodegenerative and other chronic diseases. Our experimental approach to these important topics is exceptionally broad, ranging from genetic engineering to live cell imaging to the study of molecules by X-ray crystallography, and likewise makes use of a range of genetically-tractable model organisms including mice, yeast, flies and worms.
Three ongoing initiatives
Quality Control in Biology: Understanding Disease Risk at a Molecular level
Quality control in biology refers to cellular mechanisms that detect and define “damage” incurred to biological macromolecules (e.g., DNA mutation or misfolded protein) and targets them for repair and recycling, or disposal. Failure of quality control pathways is at the source of many diseases including cancer, various neurodegenerative conditions, and aging. Quality control can also impact susceptibility to infection from pathogens such as plasmodium-causing malaria. We approach questions related to quality control at the structural, biochemical, molecular, cellular, tissue/organ, and organismic levels. This initiative builds on historically strong areas of research in the Department, including DNA repair mechanisms and posttranslational modifications of proteins, such as ubiquitination, sumoylation and, more recently, poly(ADP)-ribosylation.
The Reproductive and Developmental Origins of Health and Disease
We are interested in defining and characterizing the interrelationships between generic and epigenetic factors, nutrition, and the environment that influence the odds for a healthy life or, alternatively, determine the risk for childhood and adult-onset disease, and infertility. This initiative builds on the Division of Reproductive Biology’s expertise in the areas of germ stem cell biology, gametogenesis, and fertilization. Here again, questions are approached at the biochemical, molecular, cellular, tissue/organ, and organismic levels, such that efforts under this initiative mesh naturally with other initiatives on quality control in biology, and aging-related diseases.
Cancer and Other Aging-Related Chronic Diseases
Aging-related diseases are diseases that occur at a higher frequency with increasing age. Examples include cancer, arthritis, type 2-diabetes and several neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Lou Gehrig’s disease. Longer life expectancies are driving a steady rise in the overall incidence of these diseases in the US and throughout the world, thus demanding novel approaches for their prevention, diagnosis and treatment. This department has a long- standing interest in the molecular mechanisms and pathways responsible for the maintenance of tissue and cellular homeostasis in response to cytotoxic and genotoxic stress associated with aging, and in defining how the failure of these mechanisms progressively leads to overt disease. Through recent faculty recruitments, BMB has added significantly to its expertise in oxidative stress, inflammation biology, the role of noncoding RNAs and epigenetics, all of which play key roles in cancer and aging-related diseases.