Precision Medicine: Computational and Structural Biology
The human genome contains functional elements and protein encoding genes that are translated into proteins. Regulation of gene expression by functional elements produces specific patterns of expression in different tissues and cell types making each individual unique. It is however not currently possible to assess the impact of mutations or environmental changes that affect these genes or DNA elements that control them. Molecular Medicine investigators use a wide array of genetic, biochemical, biophysics, X ray crystallography, cryo-EM and systems biology techniques to dissect the complex regulatory networks associated with disease states like cancer, diabetes, infectious diseases and neurodevelopmental disorders.
A unique resource, Darwin’s Dogs (http://darwinsdogs.org), provides genomic data combined with behavioral data to unravel complex neurodevelopmental disorders shared between people and dogs.
Manuel Garber, PhD, associate professor of molecular medicine and bioinformatics and integrative biology, and director of the Bioinformatics Core. Dr. Garber’s methods have been critical to the discovery and characterization of a novel set of large intergenic non-coding RNAs (lincRNAs) and to our understanding of the immune transcriptional response to pathogens. In September 2012, Dr. Garber moved to the University of Massachusetts Medical School to establish his laboratory and direct the Bioinformatics core. (Garber profile)
My research uses evolution as a tool for understanding how the human genome works. By combining signals of natural selection with genome-wide association studies, I aim to identify genes, pathways, and the functional variants underlying polygenic diseases, and translate these discoveries into advances in human health care. I am currently applying these methods to understand infectious disease resistance in humans, such as cholera resistance in Bangladesh, as well as behavioral genetics in dogs. (Karlsson profile)
Crystallographic, biophysical, biochemical, and cell biological approaches are used to investigate mechanisms of membrane trafficking and cell signaling. Defects in these fundamental regulatory mechanisms play critical roles in genetically linked disorders and complex disease states including cancer and diabetes. (Lambright profile)
Treatment of many human diseases, including cancer, typically involves modulation of signal transduction pathways. These pathways are functionally integrated, very plastic, and incredibly sensitive to environmental context. Our group uses a combination of experimental and computational approaches to study the organization and function of signaling networks controlling the growth, survival, and death of cancer cells. We are particularly interested in understanding the adaptive properties that cells engage when faced with anti-cancer drugs, as well as identifying genetic, non-genetic, and contextual factors that contribute to the therapeutic variability seen in cancer patients. (Lee profile)
Type 1 Diabetes (T1D) is the result of an autoimmune destruction of insulin producing, pancreatic beta cells. The events leading to the disease have usually occurred long before diagnosis and are based on complex interactions between genes and the environment. The currently available rodent models for T1D can only represent a limited number of patients leaving open the question how many different types of T1D exist. To overcome these difficulties and expand our understanding of T1D and other diseases targeting the immune system we are building in vitro models using human pluripotent stem cells. In those stem cell-based model systems genetic and developmental aspects of the disease can be elucidated. The long-term goal is to recapitulate the disease in a patient-specific manner and to identify novel treatment strategies. (Maehr profile)