The uterine tissue lined by luminal epithelial cells undergoes periodic remodeling in response to female reproductive phases. This is necessary for the proper embryo/blastocyst implantation in the uterus subsequently pregnancy. Failure at this junction leads to loss of pregnancy. Preparation of receptive endometrium is a big obstacle in assisted reproduction. This uterine endometrium undergo various modifications, i.e. proliferation, migration, differentiation and death which are regulated by ovarian steroids while, in other cell systems, by the TGF-Β. Uterine epithelial originated TGF-Β is known to involve in stromal decidualization in a paracrine manner, at least in part .Moreover, endometrial stromal cells show proliferation, motility, and contractivity by TGF-Β in vitro, which might also be regulated by progesterone hormone. However, in spite of knowledge of the above-mentioned effects of TGF-Β, its signaling is not explored properly in the uterine tissue remodeling phases. Therefore, I have focused its signaling mechanism evaluation during uterine tissue remodeling through proteomics tools using mice model. This study will enlighten TGF- Β upstream signaling activators, which will provide its detail information in receptive uterus preparation for embryo implantation.

Despite many advances in assisted reproductive technologies (ART), implantation rates are still low. Embryo attachment and implantation is accompanied by dramatic cellular and functional changes in the endometrium, the control and mechanisms of which are not clearly understood. Transcription factors provide nodes of information integration by serving as nuclear effectors of multiple signalling cascades, and thus elaborate layers of regulation, often involving post-translational modifications, modulating and coordinating activities. Such modifications can rapidly and reversibly regulate virtually all transcription factor functions, including sub-cellular localization, stability, interactions with cofactors, other post-translational modifications and transcriptional activities. The process of embryo implantation requires a large number of molecules that intervenes the process. One such family that has been reported to implement its role is the ETS family of transcription factors. Our studies are focused mainly on the role of ETS family transcription factors in modulating the molecular mechanism of embryo implantation.

Pregnancy is an ´immunological paradox´ where the lowered immune response of the mother´s uterus favors the invasion of the embryo bearing the paternal set of genes and the successful development of the latter inside the uterine milieu. My research thrust is to understand the mechanisms involved in the regulation of immune response during pregnancy with special emphasis to embryo implantation. The study aims at identification and functional analysis of the molecules that are involved in the signaling pathways that regulate immunity at genetic as well as proteomic levels. The preliminary data generated in the lab throws some light into the non-classical function of some molecules, especially the nuclear presence of some cytosolic and membrane proteins. I am interested in elucidating these novel pathways.

Blastocyst implantation is dependent on the intrinsic embryonic program operating in conjunction with extrinsic signals emanating from the female reproductive tract. Along with the extrinsic signaling that helps the implantation of the blastocyst; there are intracellular molecules that are active at the time of implantation. The signaling molecules downstream of integrin receptor help in nuclear translocation of certain known transcription factors leading to the transcription of crucial gene products required for blastocyst implantation. My work centers around the protein moieties that help in translocation of cargo into the nucleus and to decipher the functional signature of this molecule in the nucleus. Elucidating the protein- protein interaction & the modus operandi of the nuclear translocation mediated by these signaling molecules at the window of implantation would add a new dimension to its possible mode of action and function.

Steroid hormones are one of the key regulators in the successful progression of embryo implantation. Hence their receptors also mediate crucial roles in the same. The two major receptors known are the progesterone receptors and the estrogen receptors. My arena of work is to isolate the interacting partners of Estrogen receptors alpha during embryo implantation using immunoprecipitation followed by Maldi-TOF analysis. I intend to characterize the nature of the novel proteins identified. I also wish to understand the roles of these interacting partners during embryo implantation and there impact on modulating estrogen receptor alpha action.

During early embryo development, acquisition of pluripotent nature by embryonic cells is characterized by the presence of certain proteins distinguished as stem cell markers. I would look into the defining possible factors which can act as stem cell markers and would delve into exploring whether these factors are critical for maintaining stem-cellness. My further interest is in elucidating the pathways that lead to differentiation of stem cells into committed cell types, especially the molecular mechanism leading to transition of embryonic stem cells to germ cell lineage which could provide further insights into the causes of infertility.

Polycystic ovary syndrome is a common heterogeneous, endocrine disorder found in 5% to 10% women of reproductive age. It is the first component of the metabolic-syndrome to be detected in many women. The aetiology of the syndrome still remains unclear. My work focuses on profiling the genomic & proteomic changes due to differential expression of miRNAs resulting in the manifestation of the disorder. Understanding the heterogeneity in PCOS aetiology is important in developing definitive diagnostic testing, preventive and therapeutic strategies. Future studies will provide important insight for a better understanding of the pathogenetic mechanisms underlying this clinical disorder and in turn its therapy.

In a gravid uterus there occurs a tight regulation of the immune system at the maternal and fetal interface so that the semi-allogenic embryo can survive. Embryo is semi-allogenic as it bears certain gene products as a result of parental gene expression and this represents a strong antigenic insult which would lead to immunological response. During the process of pregnancy it has been observed that there is increased infiltration of CD25+CD4+FOXP3+T-reg cells within the gravid uterus, these T-reg (FOXP3+) cells are known to suppress the activities of T-effector cells and bring in the effect commonly known as immune-tolerance. My work centers on understanding the mechanism of immune tolerance during embryo implantation and its regulation by steroid hormones.

The process of embryo implantation involves the undisputed role of reactive oxygen species as shown by our lab. Earlier work from our lab has shown that a high level of superoxide anion radical generated in the Mus musculus uterus at the window of implantation could be mediating the increased vascular permeability & other membrane reorganizations at this critical time-point. Later work from our lab established the involvement of an estrogen regulated NAD(P)H oxidase system to be responsible for superoxide generation using time lapse ESR Spectroscopy. My work centres around amplifying & cloning NOX variant of the uterus. I would also delve into understanding the impact of ROS triggered STAT signaling pathway.

The process of implantation requires immense extra-cellular matrix signaling and cytoskeletal reorganizations. Transmission of extracellular signal is mediated by ligand binding to receptor (integrins, cadherens) which activates diverse cascades and play important role during implantation. We aim to explore the cellular components of integrin signaling pathway which eventually culminates in invasion of the embryo in the the uterine invasion of the embryo. The work is mainly concentrated around the downstream integrin signaling involving cytoskeletal reorganization at the window of implantation.