https://www.stemcellsscience.info
top of page
PAX6 in neural rossettes
N CADHERIN stained neural progenitor cells
CD144 stained endothelial cells from hESCs
Phalloidin stained Actin filaments (red) in 2D cultured hESCs
Phalloidin stained Actin filaments (red) in organoids
Phalloidin stained Actin filaments (red) in 2D cultured hESCs
Epigenetic modification mechanisms
PcG regulates neuronal genes during neuronal differentiation
Effect of substrate stiffness on various mechano sensitive pathways
YAP stained (green) nuclei in hESCs in 2D culture

Funded Projects

  • Investigating the role of Polycomb group (PcG) proteins in regulating Epithelial Mesenchymal transition (EMT) & fibrotic genes in endometrium of women with stage III-IV endometriosis -  this project is on going and has been awarded Rs. 51.75 lakhs for 3 years (2024-2027) by Department of Biotechnology (DBT) project no- BT/PR43135/MED/97/609/2021.

  • Investigating the role of histone deubiquitinases in human pluripotent stem cell differentiation- this project is on going and has been awarded Rs. 33.32 lakhs for 2 years (2022-2024) by Department of Biotechnology (DBT) project no- BT/PR41465/MED/31/435/2020.

  • Investigating the osteogenic potential of extracellular vesicles loaded injectable hydrogels - this project is on-going and has been awarded Rs. 36.50 lakhs for 3 years (2021-2024) by Department of Biotechnology (DBT).

  • Understanding the activity of mechanosensors - YAP and TAZ in differentiating human pluripotent stem cells- the project was awarded Rs. 22.87 lakhs for 2 years (2019-2021) by Department of Biotechnology (DBT) project no-  BT/PR28474/MED/31/393/2018.

  • Investigating the effect of sonic hedgehog and retinoic acid signalling on polycomb group (PcGs) proteins during pancreatic lineage differentiation from pluripotent stem cells- this project was granted of Rs.40.17 lakhs for a period of 3 years (2017-2021) by Department of Science & Technology (DST) under the Early Career Researcher (ECR) scheme (ECR/2016/0051). Project no - ECR/2016/000510.

  • SVKM's NMIMS Sunandan Divatia School of Science, NMIMS (deemed to-be) University, Mumbai,  funded a one year project to understand the effect of RING1B & BMI1  inhibition on the differentiation outcome of human embryonic stem cells.

Current Project Details

Investigating the role of histone deubiquitinase BAP1 during endothelial differentiation

We are investigating the role of BAP1, a histone H2A deubiquitinase during endothelial cell differentiation from human embryonic stem cells.

We found that shRNA mediated knockdown of BAP1 resulted in reduced differentiation into endothelial cell lineage thus suggesting that BAP1 might play a role in endothelial cell differentiation

Epigenetic modifications during cell differentiation

Understanding the role of WNT Signalling in Hypertrophic Scar Formation in Post Burn Injuries

We are trying to understand how trauma injury like thermal injury alters the fibroblast cells causing them to form myofibroblasts and secrete excessive ECM.

​

We hypothesize the aberrant WNT signaling can cause conversion of fibroblasts to myofibroblasts leading to hypertrophic scar formation due to burn injury

Hypertrophic scar formation causes
Neuronal and BAP1 image.png

Investigating role of Histone H2A Deubiquitinase BAP1 during neuronal progenitor formation from human pluripotent stem cells 

​

Polycomb group proteins and other proteins catalyze various histone modifications to regulate gene expression, while other proteins remove these modifications. Our group and others have shown that H2AK119ub1 catalyzed by Polycomb Repressive Complex I (PRC1) plays a crucial role in gene regulation during neuronal lineage specification in human pluripotent stem cells. The H2AK119ub1 mark is erased by histone H2A deubiquitinases that counteract the gene repression by PRC1.

There are only about nine are histone H2A deubiquitinases namely USP3, USP12, USP16, USP21, USP22, USP44, BAP1, MYSM1 and BRCC36 and there are only few reports of these in hematopoietic stem cells. However, there are no reports of histone H2A deubiquitinases in neuronal lineage specification from human pluripotent stem cells.

We aim to study the expression of histone H2A deubiquitinases in during neuronal differentiation, as well as study the effects of shRNA-mediated knockdown of H2A- DUBs on neuronal differentiation.

EMT regulation by PcG proteins in endometriotic tissue

Epithelial to mesenchymal (EMT) transition enables endometrial tissue to move to ectopic sites. We hypothesize that Polycomb group (PcG) proteins may mis-regulate the EMT genes leading to endometriosis.

Endometriosis is a condition in which functional endometrial glands and stroma grow outside of the uterine cavity and this growth leads to complications such as dysmenorrhea, dyspareunia, chronic pelvic pain, adhesions and infertility, with fibrosis routinely observed and this further contributes to pain and infertility. However, the epigenetic mechanism that leads to EMT and fibrosis in endometriosis is poorly understood. Polycomb Group (PcG) proteins are histone modifiers that can control the expression of genes involved in EMT by catalysing histone modifications; their misexpression is reported in several cancers. We hypothesise that misregulation of PcGs could lead to overexpression of EMT related genes, which may help endometrial cells migrate and cause fibrosis ectopically.

To determine this, we plan to study if the PcGs protein occupy promoters and regulate EMT and fibrosis genes in ectopic endometrial cells as well when specific PcG (RING1B and EZH2) genes are repressed.

Summary of the research being done in specific areas
Epigenetic modifications during cell differentiation

Human Pluripotent Stem Cell Differentiation & Epigenetics

​

Polycomb group (PcG) proteins along with other epigenetic modulators catalyse histone modifications at promoters and thus they control the expression of genes essential for lineage specification.

Human pluripotent stem cells are the cells with miraculous ability to self-renew and differentiate into all three-germ lineage. Decades of research has shown that transforming pluripotent stem cells into a mature functional tissue is a difficult task. Thus it in order to decipher this intricate process, we have to understand the mechanism of cell differentiation and maturation.

Currently we are pursuing research to understand how Polycomb group (PcG) proteins respond to differentiation cues and add inhibitory histone modifications (H3K27me3 & H2AK119ub1) at the promoters of crucial genes in human pluripotent stem cells

Research questions that are to be investigated

  • How do RING1B and BAP1 crosstalk in human pluripotent stem cells?

  • What is the role of BAP1 and RING1B in formation of trophoblast cells that makes the placenta?​

  • Can epigenetic modifiers alter the 3D chromatin structure ?​​

bottom of page