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Cell shape modulates cellular response to stimuli

Demonstrated that the cell shape can modulate the transcriptional response to external stimuli such as compressive load and inflammation.
Paper1 Paper2

Measuring the contribution of cell mechanics to the selective activation of fibroblasts by cancer

Established the existence of activation primed cell shapes using multimodal-multivariate analysis. Demonstrated a causal relationship between cell geometry and activation. In addition, our study presents a framework for studying single cell heterogeneity and highlights the importance of the geometric state of fibroblasts in the interpretation of environmental signals.
Paper Poster

publications

Nuclear Positioning and Its Translational Dynamics Are Regulated by Cell Geometry.

Radhakrishnan AV, Jokhun DS, Saradha Venkatachalapathy, and Shivashankar GV

Published in Biophysical Journal, 2017

This paper explores how the positional dynamics of the nucleus is modulated in cells of different shapes

Cell geometry dictates TNFα-induced genome response

Mitra A, Saradha Venkatachalapathy, Ratna P, Wang Y, Jokhun DS, and Shivashankar GV

Published in Proceedings of the National Academy of Sciences, 2017

In this work we demonstrate cells of different shapes respond differently to inflammatory cues Paper Science Feature

Network analysis identifies chromosome intermingling regions as regulatory hotspots for transcription.

Belyaeva A,Saradha Venkatachalapathy, Nagarajan M, Shivashankar GV, and Uhler C

Published in Proceedings of the National Academy of Sciences, 2017

This study demonstrates that the inter chromosomal contacts are crucial elements of transcription regulation.

Laterally confined growth of cells induces nuclear reprogramming in the absence of exogenous biochemical factors

Roy B, Saradha Venkatachalapathy, Ratna P, Wang Y, Jokhun DS, Nagarajan M, and Shivashankar GV

Published in Proceedings of the National Academy of Sciences, 2018

In this paper we describe a novel method of reprogramming fibroblasts to iPSC-like cells.

Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response

Damodaran K#, Saradha Venkatachalapathy#, Alisafaei, Radhakrishnan AV, Sharma Jokhun D, Shenoy VB, and Shivashankar GV (#Equal contribution)

Published in Molecular Biology of the Cell , 2018

In this work we show that when given the same compressive force stimulus, cell of different shapes have different transcriptional response

Multivariate analysis reveals activation-primed fibroblast geometric states in engineered 3D tumor microenvironments.

Saradha Venkatachalapathy, Doorgesh Sharma Jokhun, and G. V. Shivashankar

Published in Molecular Biology of the Cell, 2020

In this study, we map fibroblast cell shapes to their activation level and demontrate a causal relationship between the two.

Predicting cell lineages using autoencoders and optimal transport

Karren Dai Yang, Karthik Damodaran, Saradha Venkatachalapathy, Ali C Soylemezoglu, GV Shivashankar, Caroline Uhler

Published in PLoS computational biology, 2020

This paper presents an approach to model lineages from images:ImageAEOT.

Multi-domain translation between single-cell imaging and sequencing data using autoencoders.

Karren Dai Yang, Anastasiya Belyaeva, Saradha Venkatachalapathy, Karthik Damodaran, Abigail Katcoff, Adityanarayanan Radhakrishnan, GV Shivashankar, Caroline Uhler

Published in Nature Communications, 2021

This paper presents an approach to translate between data modalities via a shared latent space

talks

Nuclear positioning and its translation dynamics is regulated by cell geometry

Published: September 27, 2016

Poster presentation at Biophysical Society-MBI Thematic Meeting: Mechanobiology of Disease

Authors: Radhakrishnan AV,Saradha Venkatachalapathy,Shivashankar G.V.

Abstract
The collective activity of several molecular motors and other active processes generate large forces for directional motion within the cell and a background of fluctuating forces. These processes are vital for a multitude of cellular functions such as migration, division and contraction. In addition, they can also influence the transport and positioning of many cellular organelles by affecting their intracellular dynamics. This creates unique biophysical signatures which are altered in many diseases. In this study, we have used the nucleus as a probe particle to understand the micro-rheological properties of the cytoplasm by using micropatterning techniques to confine cells in two structurally and functionally extreme geometries. We find that nuclear positional dynamics is sensitive to the cytoskeletal organization by studying the effect of actin polymerization, nuclear rigidity, and TNFα cytokine stimulation on the position and diffusive behavior of the nucleus. Taken together, our results suggest that mapping nuclear positional dynamics provides important insights into biophysical properties of the cytoplasm. These biophysical signatures could also be used as an ultrasensitive single-cell assay for early disease diagnostics.

Role of 3D chromatin architecture in differential genome regulation

Published: December 11, 2017

Gave a talk at the 3rd International Symposium on Mechanobiology

Role of cell geometry and 3D chromatin structure in differential genome regulation

Published: April 17, 2018

Gave a talk at EMBO Workshop: Nuclear Mechanogenomics

Heterogeneity in cell geometric states regulate the selective activation of fibroblasts in engineered 3D tumor microenvironment

Published: November 07, 2018

Poster presentation at Mechanobiology after 10 Years: The Promise of Mechanomedicine

Authors: Saradha Venkatachalapathy,Shivashankar G.V.

teaching

Teaching experience 1

Undergraduate course, University 1, Department, 2014

This is a description of a teaching experience. You can use markdown like any other post.

Teaching experience 2

Workshop, University 1, Department, 2015