Our Advisory Board

Research in the Subramaniam laboratory spans several areas of bioinformatics, systems biology and medicine. In bioinformatics, he is involved in developing novel strategies for identifying protein interaction networks, intracellular localization of proteins and identification of functional networks in cells. In systems biology, he is involved in deciphering mammalian cellular networks from high throughput and phenotypic data and in developing strategies for modeling cellular signaling networks. In systems medicine, he collaborates with biomedical scientists towards understanding diseases associated with insulin resistance and inflammation. His laboratory is interested in mapping the circuitry of cells to mechanisms and phenotypes in physiology and pathology and to develop quantitative models of cellular pathways.

The human brain contains around 100 billion neurons. Their genesis, development and degeneration are all governed by underlying gene regulatory networks (GRNs). These fundamental biological processes represent a nexus where basic and translational neurobiology converge; the same processes that orchestrate normal neuronal development, maturation and death are those that malfunction in neurodevelopmental and neurodegenerative disorders. We aim to identify these networks and uncover how they vary across individuals, thereby causing errors of neurodevelopment or susceptibility to neurodegeneration. This overarching goal is as much about developing a basic understanding of how neuronal phenotype emerges from interactions among the genes of the network as it is about translating this understanding into identification of novel therapeutic targets. All of our work is guided by a credo that understanding basic biological mechanisms and identifying targets for therapeutic intervention are inextricably intertwined. To implement this vision, we work collaboratively with basic, clinical and translational neuroscientists, molecular biologists, stem cell biologists and computational biologists.

The major research thrusts in the Mali laboratory can be categorized as follows: one, development of genome and transcriptome engineering toolsets and their application to systematic genome interpretation and gene therapy applications; and two, study and engineering of gene regulatory networks and cellular niches governing cell fate specification during development utilizing human pluripotent stem cells as the core model system. Given the parallels in phenotypes (such as self-renewal and tumor forming ability) between pluripotent stem cells and cancer cells, a key research thrust is also in dissecting aberrant cellular transformation processes such as during tumorigenesis. As such, the research program lies at the interface of technology development and basic science, and combines core expertise in synthetic biology and regenerative medicine, with instrumentation and materials engineering.