Sumithra Sankararaman, Ph.D.
Year in Program: Second Year
Rob Mitra, Ph.D.
Alvin Goldfarb Distinguished Professor
of Computational Biology
Department of Genetics
Washington University School of Medicine
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Dr. Sumithra Sankararaman has a background in Biophysics, and is originally from India. She is working with her primary mentor, Dr. Mitra, and her primary interest over the past year has been to investigate various mechanisms involved in gene regulation at the transcriptional level and at the epigenetic level, and to develop mathematical models and associated tools that might be applied in the design of new genetic research and therapeutic interventions.
Project: Studying the effect of transcription factor dynamics on gene expression output
Cellular response to extracellular stresses is determined by the regulation of a set of target genes via different signaling pathways. Very often, information about the identity and attributes of diverse stresses are transmitted to the target genes by a small set of signaling molecules to generate an appropriate outcome. The specificity of cellular response to diverse signals is thought to be governed by the dynamics of a signaling molecule translocating into the nucleus. Thus, changing the dynamics of the nuclear translocation of a relevant transcription factor may result in changes in the expression of downstream genes that will influence cellular fate decisions.
Based on such studies, we investigated the possibility of constructing a synthetic "frequency-filter" in which the frequency modulation of the transcription factor input would lead to the differential expression of multiple target genes with different promoter characteristics. In addition to this, if the target genes expressed mutual repressor proteins, we can expect to see a dramatic effect in expression output in terms of which set of genes are expressed and which are repressed as a function of input frequency.
Project: Studies on profiling differential methylation patterns in mouse stem cells and motor neurons
Emerging evidence suggests the importance of epigenetic regulation in activity-dependent brain functions such as learning and memory, circadian rhythm, drug addiction and neurogenesis. Recent work reported in  shows that neuronal activity changes the DNA methylation activity in the adult mouse brain. This led us to investigate the possibility of studying differential methylation patterns in the early and late stages of development of motor neurons and glial cells. Such an analysis will inform about the time course of the methylation changes in the brain as neural or brain cells develop for a better understanding of stimulus-induced methylation changes due to the brain functions.
Sankararaman, S. (Oral presentation): Transcriptional control of gene expression via frequency modulation of the transcription factor input. R. Mitra Lab meeting, Washington University School of Medicine, Saint Louis, MO, 16 Aug 2013.
Sankararaman, S. (Oral presentation): How are external cellular signals transduced into transcriptional response?. NIH/NIDA Genetics Consortium Winter Meeting, Rockville, MD, Nov 2013.
Sankararaman, S. (Oral Presentation): Designing a frequency filter in a genetic system. R25 Fellowship Symposium: Statistical and Computational Innovation in Addiction Genetics, Washington University School of Medicine, Saint Louis, MO, December 2013.