Molecular and Cellular Biology

About Us

The research carried out in our lab is focused on 1) Understanding of factors that govern initiation and maintenance of pregnancy and 2) Genetic basis of gonadal development and infertility. The experimental approaches used in the lab include cell culture, transgenic mice and knockout mice, microscopy, live imaging and various biochemical and molecular techniques.

Endometrial functions and dysfunctions

For initiation of pregnancy, the mammalian uterus goes through series of events including implantation, decidualization, placentation and parturition. The failure to complete any of these well-orchestrated events results in implantation failure, spontaneous miscarriage or preterm birth. Our laboratory is involved in dissecting the molecular events that govern initiation of pregnancy and understanding the causes of such failures (Ashary et al 2018). Our group was the first to demonstrate that embryo implantation involves extensive cross talk with the maternal uterus which is a pre-requisite for a successful pregnancy. The current focus of the work is on the mechanisms by which the transcription factor HOXA10 signaling mediates uterine function during the establishment of pregnancy. Using human cell lines, and mouse as study models, the lab has demonstrated how endometrial HOXA10 controls stromal cell differentiation to promote placentation (Godbole et al 2017).  In addition, the laboratory has developed a transgenic mouse hypomorphic for HOXA10 where the focus is to understand the etiology of endometrial diseases like hyperplasia, endometriosis and endometrial cancers. The lab has also recently got interested in understanding how maternal infections affect the feto-maternal cross talk leading to pregnancy complications (Surve et al 2016). We hope this work will help in diagnosis and management of infertility, improve success rates of IVF and prevent preterm births.

Molecular mechanism involved in gonad development

Another area which the lab is interested is in determining how the gonads are developed and they decide to become the testis or an ovary. During development, the early embryonic gonad are bipotential and can switch to become a testis or ovary. In mammals this usually switch depends on the presence or absence of the Sry gene on Y chromosome (males are XY, females XX). Downstream of this dominant genetic switch are complex signaling pathways that determine the fate of gonadal cells, mainly the somatic cells. While our understandings of the molecular mechanisms of sex determination in the somatic cells are clear, how the germ cells decide to form the male or the female gamete is yet not understood. We are interested in determining the mechanisms involved in sex determination in the germ cells and if there exist any cross talk between the germ and somatic to govern sex determination in the gonads. This work is envisaged to help in expanding our understanding of disorders of sexual development and infertility.

Translational research       

The translational research endeavors in the laboratory are developing molecular diagnostic tools. Presently, we are in the process of developing a PCR kit to detect Yq microdeletions in infertile males. This kit is meant for use in clinics to diagnose the cause of male infertility and also counsel the men to make a rational choice in preventing the vertical transmission of the genetic defects in his male progeny (Colaco and Modi 2018).  We are also keen to develop diagnostic modalities for detection of vaginal infections related to preterm births.

Godbole et al 2017

Ashray et al

Colaco and Modi

Surve et al

People

Department Email Id: mcbl@nirrh.res.in 

Projects

1. Deciphering the role of homeobox protein HOXA10 in endometrial receptivity and decidualization (Funded by Department of Biotechnology)

2. Identification and characterization of a novel transmembrane receptor for progesterone (Funded by ICMR Medical Innovation Grant)

3. Sperm Phospho-Proteomics: Elucidating the Signal Transduction Mechanisms of Progesterone Action (Funded by Department of Biotechnology)

4. Identification and characterization of progesterone receptors in human testis and spermatozoa (Funded by ICMR-NIRRH core grant)