Andrea Califano, Ph.D. Columbia University Medical Center
We have developed network-based methodologies for the systematic identification, validation, and pharmacological targeting of a new class of therapeutic targets. These targets comprise Master Regulator proteins, whose concerted activity within a Regulatory Checkpoint module is responsible for the mechanistic implementation and maintenance of cell transcriptional state, in both transformed and non-transformed cells.
Eric Greene, Ph.D. Columbia University Medical Center
Homologous recombination (HR) is essential for maintenance of genome integrity. Rad51 paralogs fulfill a conserved but undefined role in HR, and their mutations are associated with increased cancer risk in humans. We have used single-molecule imaging to reveal that the Saccharomyces cerevisiae Rad51 paralog complex Rad55-Rad57 promotes assembly of Rad51 recombinase filament through transient interactions, providing evidence that it acts like a classical molecular chaperone. Srs2 is an ATP-dependent anti-recombinase that downregulates HR by actively dismantling Rad51 filaments.
The first approved gene therapy in the Western world, alipogene tiparvovec, gained conditional approval by the European Medicines Agency in 2012. This lecture will review the progress of gene therapy since, including currently approved products and those in late-stage testing. Hurdles to approval, including the need to build regulatory infrastructure, and in some cases, the need to develop novel endpoints for diseases never before treated, will be discussed.
The molecular pathophysiology of chronic pain is largely unknown. The genetic and molecular studies of human pain can nevertheless provide critical insights into pathophysiological mechanisms of pain “chronification,” the process of transient pain progressing into persistent pain. Genome-wide “omics” approaches allow a whole human genome scan that is hypothesis-free and permit systematic use and integration of multiple genome-wide datasets, resulting in unbiased interpretation of data. In this talk, Dr.
Key Lecture Points: Adult reproductive fitness traits can be regulated by local cell behaviour decisions during early development. No single “smoking gun” gene regulatory network regulates complex reproductive trait. Environment-sensing molecular mechanisms may link heritability and plasticity. Establishing null expectations for evolutionary changes helps focus the search for adaptive mechanisms. Nothing explains everything: broad taxon sampling is still important
Birds "sing" using a unique vocal organ called the syrinx. It is an example of the evolution of a novel structure. We have explored the genetic pathways underlying the embryonic formation of the syrinx to understand its morphogenesis and to understand how this adaptation arose.
Sangeeta Bhatia, M.D., Ph.D. Koch Institute for Integrative Cancer Research at MIT
Our laboratory studies how micro- and nanoscale systems can be deployed to understand, diagnose, and treat human disease. In this talk, I will describe our progress in two application areas: liver disease and cancer. In the area of the liver, we are developing microtechnology tools to understand how ensembles of cells coordinate to produce tissues with emergent properties in the body. We have used this understanding to fabricate human microliver tissues in both ‘2D’ and ‘3D’ formats that enable us to study the pathogenesis of relapsing malaria and liver regeneration.
In this lecture, Dr. Singleton will cover his laboratory’s work aimed at unraveling the genetics of Parkinson’s disease. This work has resulted in the identification of a large number of causal risk variants and risk loci forming the basis for much of the current mechanistic research and providing targets for therapeutic intervention. He will discuss how genetics has evolved into highly collaborative team science, and how using the capabilities and position of the Intramural Research Program has been critically important in shaping this work.
This page was last updated on Thursday, November 18, 2021
