Priya Sivaramakrishnan, MSc., PhD.

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Assistant Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
Colket Translational Research Building
Room 9022 (Office), 9200 (Lab)
3501 Civic Center Blvd
Philadelphia, PA 19104
BSc. (Zoology)
Stella Maris College (University of Madras), 2006.
MSc. (Human Genetics )
Sri Ramachandra University , 2008.
PhD. (Molecular and Human Genetics )
Baylor College of Medicine , 2017.
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Description of Research Expertise

Research Interests

We are interested in understanding how the dynamics of fundamental cellular processes are fine-tuned in developing cells; and apply single-cell imaging and sequencing approaches to uncover principles that drive cell identity establishment and how these can be dysregulated in disease states.


Gene regulation, development, cell fate programming, transcriptomics, single-cell imaging

Research Details

In rapidly growing and dividing cells, precise spatio-temporal coordination of basic processes such as transcription and DNA replication is essential for cellular decision making. We use the C. elegans embryo as a model to capture and quantify the dynamics of these processes during developmental cell fate programming. C. elegans embryonic development is invariant, proceeding through highly reproducible division patterns, resulting in an identical set of 558 terminal cells at the time of hatching. We can track the development of each individual cell, identify lineage trajectories, and characterize detailed fate changes in mutant and perturbed individuals, allowing us to directly link molecular dysregulation with developmental defects.

Gene expression programs that control when genes are turned ON are central to cellular programing. The steps involved in these programs are complex and dynamic, occurring in a crowded nuclear space. We are working towards systematically investigating each step and examining their impact on cellular fate decisions in individual cells. Current projects include looking at how the spatial organization and the different stages of transcription contribute to overall dynamics and mRNA accumulation, studying the patterns of replication origin firing and its role in preventing replication-transcription conflicts, connecting mechanisms that buffer transcription noise to invariant fate decisions, and generating humanized C. elegans to investigate the molecular basis of transcription-associated developmental disorders.

Rotation Projects

(1) Contributions of different transcription steps to total RNA dynamics. Test the impact of initiation (using CRISPR, synthetic arrays), elongation (DRB-seq, mutants) and spatial organization (imaging) to mRNA output and developmental outcomes

(2) Can we connect noisy transcription to specific fate defects? Developing combined live RNA imaging (MS2 or RNAi-based) and lineage tracing methods (confocal imaging followed by automated lineage analysis) to investigate mechanisms that buffer transcription noise and promote high-fidelity fate decisions

(3) Coupling cell size to transcription dynamics. Test the hypothesis that cell size might control transcription rates of cell fate regulators using RNAi and degron alleles to manipulate cell size and characterize transcriptome changes by single-cell RNA sequencing and single molecule FISH.

(4) Understanding variable expressivity and penetrance using worm models of human transcription-associated developmental disorders. Mutations in gene associated with general transcription factors show a range of phenotypes, but the molecular mechanisms are not known. By generating humanized worms and knocking-in a human variant of interest, we can connect transcriptome changes with cell fate defects.

(5) Examining replication-transcription conflicts in the rapidly dividing embryo. Mapping the dynamics of replication origin firing in connection with high-rate transcription of cell fate regulators.

Selected Publications

Sivaramakrishnan, P., Watkins, C., Murray, J.I.: Transcript accumulation rates in the early Caenorhabditis elegans embryo. Science Advances 9(eadi1270), 2023.

Sivaramakrishnan, P., Sepúlveda, L.A., Halliday, J.A., Núñez, M.A.B., Liu, J., Golding, I., Rosenberg, S.M. and Herman, C.: The transcription fidelity factor GreA impedes DNA break repair in Escherichia coli. Nature 550(214-218), 2017.

Packer J.S., Zhu, Q., Huynh, C., Sivaramakrishnan, P., Preston, E., Dueck, H., Stefanik, D., Tan, K., Trapnell, C., Kim, J., Waterston, R.H., Murray, J.I.: A lineage-resolved molecular atlas of C. elegans embryogenesis at single-cell resolution. Science(eaax1971), 2019.

Sivaramakrishnan, P., Bradley, C.C., Artsimovitch, I., Hagstrom, K.M., Ramirez, L.D., Wen, A.C., Cooke, M.B., Shaulsky, M., Herman, C., Halliday, J.A.: Modulation of RNA polymerase processivity affects double-strand break repair in the presence of a DNA end-binding protein. bioRxiv 2022.

Murray, J.I., Preston, E., Crawford, J.P., Rumley, J.D., Amom, P., Anderson, B.D., Sivaramakrishnan, P., Patel, S.D., et al.: The anterior Hox gene ceh-13 and elt-1/GATA activate the posterior Hox genes nob-1 and php-1 to specify posterior lineages in the C. elegans embryo. PLoS Genet 18(e1010187), 2022.

Han, B., Sivaramakrishnan, P., Lin, C.J., He, J., Tay, L.R., Sowa, J.N., Sizovs, A., Du, G., Wang, J., Herman, C. and Wang, M.C.: Microbial Genetic Composition Tunes Host Longevity. Cell 169(1249-1262), 2017.

Neve, I.A.A., Sowa, J.N., Lin, C.J., Sivaramakrishnan, P., Herman, C., Ye, Y., Han, L., Wang, M.C.: Escherichia coli Metabolite Profiling Leads to the Development of an RNA Interference Strain for Caenorhabditis elegans. G3 (Bethesda) 10: 189-198, 2020.

Poleshko A., Smith C.L., Nguyen S.C., Sivaramakrishnan, P., Wong, K.G., Murray, J.I., Lakadamyali, M., Joyce, E.F., Jain, R., Epstein, J.A.: K3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis. eLife 8(e49278), 2019.

Sivaramakrishnan, P. and Murray, J.I.: Neurogenesis: Silencing the alternative. eLife 8(e49635), 2019.

Zhang, Y., Mooney, R.A., Grass, J.A., Sivaramakrishnan, P., Herman, C., Landick, R., and Wang, J.D.: DksA guards elongating RNA polymerase against ribosome-stalling-induced arrest. Mol Cell 53(766-778), 2014.

Satory, D., Halliday, J.A., Sivaramakrishnan, P., Lua, R.C., and Herman, C.: Characterization of a novel RNA polymerase mutant that alters DksA activity. J Bacteriol 195(4187-4194), 2013.

Wimberly, H., Shee, C., Thornton, P.C., Sivaramakrishnan, P., Rosenberg, S.M., and Hastings, P.J.: R-loops and nicks initiate DNA breakage and genome instability in non-growing Escherichia coli. Nat Commun 4(2115), 2013.

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Last updated: 02/13/2024
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