Prof Srikala Raghavan - Epithelial Homeostasis and Immune Regulation at Barrier Surfaces

Introduction

LeQuesne John

The mammalian skin is an excellent model system to functionally interrogate fundamental cell biological processes required for epithelial homeostasis. The intricate and dynamic relationship between cell adhesion, migration, and basement membrane organisation, in the context of the local immune microenvironment, is critical to normal skin development and healthy tissue function. Gaining insight into the complex interplay between these processes allows us to understand how they go awry in pathological conditions such as inflammatory skin disorders and cancer.

Our work is organized into two major research programs:

1. Epithelial-Immune Metabolic Crosstalk and Inflammatory Skin Diseases. This program focuses on understanding the crosstalk between epithelial cells, immune cells, and the extracellular matrix (ECM) in maintaining homeostasis and exploring the metabolic drivers of inflammatory skin diseases and cancer.

Epithelial Immune Metabolic Crosstalk and Inflammatory Skin Diseases Image

2. Stem Cell Homeostasis and Nuclear Mechanosensing. This program focuses on understanding the mechanical underpinning of the crosstalk between the ECM and cell junctions with the cytoskeleton and nucleus in maintaining stem cell quiescence and the role altered nuclear mechanotransduction in driving diseases such as metastatic cancers.

Stem Cell Homeostasis and Nuclear Mechanosensing Image

Lab Report

Key Publications

Kurbet A, Hegde S, Bhattacharya O, Marepally S, Vemula PK, Raghavan S. Sterile Inflammation Enhances ECM Degradation in Integrin β1 KO Embryonic Skin. Cell Reports. 2016;Sep 20;16(12):3334-47.

Bansal D, Kulkarni J, Nadahalli K, Lakshmanan V, Krishna S, Sasidharan V, Geo J, Dilipkumar S, Pasricha R, Gulyani A, Raghavan S, Palakodeti D. Cytoplasmic poly (A)-binding protein critically regulates epidermal maintenance and turnover in the planarian. Schmidtea mediterranea. 2017;Sep 1;144(17):3066-3079.

Krishna S, Yim DG, Lakshmanan V, Tirumalai V, Koh JL, Park JE, Cheong JK, Low JL, Lim MJ, Sze SK, Shivaprasad P, Gulyani A, Raghavan S*, Palakodeti D*, DasGupta R*. Dynamic expression of tRNA-derived small RNAs define cellular states. EMBO Rep. 2019;Jul;20(7):e47789. (*co-corresponding authors).

Bhattacharjee O, Ayyangar U, Kurbet AS, Ashok D, Raghavan S. Unravelling the ECM-Immune Cell Crosstalk in Skin Diseases. Front Cell Dev Biol. 2019;May 7;7:68.

Kurbet AS, Raghavan S. Isolating Immune Cells from Mouse Embryonic Skin. Methods Mol Biol. 2019;1879:299-305.

Raghavan S, Vasioukhin V. Staying connected under tension. Science. 2020;Nov 27;370(6520):1036-1037.

Krishna S, Raghavan S, DasGupta R, Palakodeti D. tRNA-derived fragments (tRFs): establishing their turf in post-transcriptional gene regulation. Cell Mol Life Sci. 2021;Jan 2.

Biswas R, Banerjee A, Lembo S, Zhao Z, Lakshmanan V, Lim R, Le S, Nakasaki M, Kutyavin V, Wright G, Palakodeti D, Ross RS, Jamora C, Vasioukhin V, Jie Y, Raghavan* S. Mechanical instability of adherens junctions overrides intrinsic quiescence of hair follicle stem cells. Dev Cell. 2021;Mar 22;56(6):761-780.e7. [*Cover Image]

Dev Cell Cover

Banerjee A, Biswas R, Lim R, Pasolli HA, Raghavan S. Scanning electron microscopy of murine skin ultrathin sections and cultured keratinocytes. STAR Protoc. 2021;Aug 17;2(3):100729.

Bhattacharjee O, Ayyangar U, Kurbet AS, Lakshmanan V, Palakodeti D, Ginhoux F, Raghavan S. Epithelial-Macrophage Crosstalk initiates Sterile Inflammation in Embryonic Skin. Frontiers in Immunology 2021;Oct 14;12:718005.

Lim R, Banerjee A, Biswas R, Chari A, Raghavan S. Mechanotransduction through adhesion molecules: Emerging roles in regulating the stem cell niche. Front Cell Dev Biol. 2022; 10 966662. 12 Sep. 2022.

Wang J, Fu Y, Huang W, et al. MicroRNA-205 promotes hair regeneration by modulating mechanical properties of hair follicle stem cells. Proc Natl Acad Sci U S A. 2023;120(22):e2220635120.

Ayyangar U, Karkhanis A, Tay H, Afandi AFB, Bhattacharjee O, Ks L, Lee SH, Chan J, Raghavan S. Metabolic rewiring of macrophages by epidermal-derived lactate promotes sterile inflammation in the murine skin. EMBO J. 2024; Apr;43(7):1113-1134. [*Cover Image]

EMBO Cover