Prof. Rita Singh
In residence at
Dr Pascale Crépieux
Prof Rita Singh is a Professor in University of Delhi, a teacher for master students specialising in Molecular endocrinology and Reproduction. She did her PhD from University of Delhi in 1990 and since then her scientific research involves the biochemistry of gonadotropins, their receptor signaling, the molecular and metabolic defects in polycystic ovary syndrome (PCOS). She was a member of 9th Indian expedition to Antarctica in 1989. She has past affiliations with Medical school of University of Pennsylvania, USA, Virginia commonwealth University, and NUS, Singapore. She has received several prestigious awards such as LS Ramaswami oration award and gold medal for outstanding work in Reproductive health, Crest award for study on Cancer stem cells and Young Scientist award from Ministry of Science and Technology, India. She is a task force member in Environment ministry, HRD ministry and Indian council of Medical research. Not only her work on gonadotropin receptor signaling and defects in Polycystic ovary syndrome (PCOS) are well recognized, but also her various societal awareness programs in schools and colleges on the impact of environmental endocrine disruptors like plastics on the health of children and adolescents.
Interaction between the FSH receptor and Insulin receptor substrates (IRS-1 and IRS-2) in the physiopathology of the polycystic ovary syndrome
Background: Polycystic ovary syndrome (PCOS) is a genetically complex disorder often associated with elevated luteinizing hormone (LH), arrested follicular growth and subfertility/infertility. These women with high LH have difficulty in conceiving and gestational diabetes affects 50-61% of all PCOS pregnancies. Based on our earlier data, we hypothesize that the activation of insulin signaling components like insulin receptor substrates are severely impacted when there is hypersecretion of LH in PCOS women. Novelty: To elucidate the cause of metabolic abnormalities in PCOS, the focus of this study is to unravel the defects in the cross-talk between FSHR and Insulin receptor substrates (IRS-1 and -2) in the presence of high LH /hCG
1. To examine the mechanism of interaction of Insulin receptor substrates (IRS-1 and IRS-2) with FSHR, LHR and their signaling components.
2. To understand the role of Galpha/beta-arrestin in the cross-talk between FSHR and LHR signaling pathways.
3. To explore the role of LH-stimulated Ca2+ response in the attenuation of FSH responses.
Methods: Bioluminescence Resonance Energy Transfer (BRET) measurement will be done in HEK-293 cells after co-transfection with Luc8- and Venus-labelled FSHR, LHR, or Galpha and beta-arrestin, respectively in the presence of hormones with appropriate controls. The impact of high LH on FSH- and insulin-mediated glucose uptake and glycogen level coinciding with the structural changes observed by BRET using IRS-1 and IRS-2 as probes. High LH-stimulated Ca2+ responses will be monitored in HEK293 cells co-expressing FSHR and LHR.
Expected Outcomes: This study will elucidate the mechanism by which high LH may induce abnormal structure-function changes in the FSHR on binding with FSH. Heteromerization of FSHR and LHR coinciding with a decrease in sensitivity of FSH through change in the proximity of IRS proteins is expected. This study will be the first of its kind to establish adverse molecular changes in the signaling components of FSH and their cross-talk with IRS-1 and IRS-2 in the presence high LH.
Publications in relation with the research project
Malaria is one of the most important parasitic infection in the world. Cerebral and pulmonary complications may occur after infection and are often lethal. Immune response plays an important role in controlling malaria infection; however, excessive inflammatory response can lead to severe disease. The present work aims to decipher the cellular and molecular events associated with brain and pulmonary pathology in response to blood stage Plasmodium berghei ANKA (PbA) infection. PbA infection in C57BL/6 wild-type (WT) mice induces experimental cerebral malaria (ECM), associated with strong pro-inflammatory response, brain damage, as well as paralysis, coma early death (around day 7 p.i.). Interestingly, IFNγ receptor deficient mice (IFNγR1-/-, C57BL/6 background) are resistant to ECM and died at a later time-point, due to the hyperparasitaemia and severe anemia. Here, we addressed the impact of IFNγR1 deficiency in the development of pulmonary damage during PbA infection. At day 7 post-infection, the broncho-alveolar lavage (BAL) allowed the quantitative analysis of total cells and proteins in the broncho-alveolar space of the animals. In addition, histological analysis and Western blot were performed to compare the cerebral and pulmonary compartments. As compared to PbA-infected WT mice, the histological sections confirmed a less intense accumulation of leukocytes as well as an absence of hemorrhages in the brains of IFNγR1-/- mice. In addition, the quantification of pro-apoptotic proteins (Granzyme B and cleaved caspase-3) in olfactory bulbs showed lower levels in IFNγR1-/- mice. While IFNγR1 deficient mice were fully resistant to brain pathology, those mice were partially protected for pulmonary damage, as observed by the levels of Granzyme B and cleaved caspase-3 in the lung parenchyma, leukocyte number in the broncho-alveolar space and pulmonary edema.