Madhuri Salker

• MRSB PhD
• Group Leader at Universitätsklinikum Tübingen

Cell stiffness is regulated by dynamic interaction between ras-related C3 botulinum toxin substrate 1 (Rac1) and p21 protein-activated kinase 1 (PAK1) proteins, besides other biochemical and molecular regulators. In this study, we investigated how the Placental Growth Factor (PlGF) changes endometrial mechanics by modifying the actin cytoskeleton a...

Nuclear factor of activated T cells 5 (NFAT5) and cyclooxygenase 2 (COX2; PTGS2) both participate in diverse pathologies including cancer progression. However, the biological role of the NFAT5-COX2 signaling pathway in human endometrial cancer has remained elusive. The present study explored whether NFAT5 is expressed in endometrial tumors and if N...

Background: Braak's hypothesis states that sporadic Parkinson's disease (PD) follows a specific progression of pathology from the peripheral to the central nervous system, and this progression can be monitored by detecting the accumulation of alpha-Synuclein (α-Syn) protein. Consequently, there is growing interest in understanding how the gut (com...

COVID-19 vaccines based on a range of expression platforms have shown considerable protective efficacy, generating antibody and T cell immune responses. However, molecular pathways underpinning COVID-19 vaccine priming of immunity against the SARS-CoV-2 virus have not yet been explored extensively. This analysis is critical to optimization of futur...

COVID-19 vaccines based on a range of expression platforms have shown considerable protective efficacy, generating antibody and T cell immune responses. However, molecular pathways underpinning COVID-19 vaccine priming of immunity against the SARS-CoV-2 virus have not yet been explored extensively. This analysis is critical to optimization of futur...

Both COVID-19 mRNA or recombinant Adenovirus vector (rAdVV) based vaccines have shown great efficacy in generating humoral and cellular immune responses. Two doses of the COVID-19 vaccines generate enough antibodies and generate spike-specific T cell responses. However, after 6-8 months there is a decline in antibody production and T cell responses...

Pregnancy is a complex phenomenon during which women undergo immense immunological change throughout this period. Having an infection with the SARS-CoV-2 virus leads to an additional burden on the highly stretched immune response. Some studies suggest that age-matched pregnant women are more prone to SARS-CoV-2 infection compared with normal health...

The association between maternal COVID-19 infection, placental histomorphology and perinatal outcomes is uncertain. The published studies on how placental structure is affected after SARS-CoV-2 virus in COVID-19-infected pregnant women are lacking. We investigated the effects of maternal SARS-CoV-2 infection on placental histomorphology and pregnan...

A successful pregnancy outcome is dependent on a delicate balance between inflammatory and anti-inflammatory processes throughout the different trimesters. Interruption in this balance can lead to an adverse outcome resulting in pregnancy loss. Since late 2019, the emergence of the new SARS-CoV-2 virus has affected lives worldwide, including pregna...

Whilst scientific knowledge about SARS-CoV-2 and COVID-19 is rapidly increasing, much of the effects on pregnant women is still unknown. To accommodate pregnancy, the human endometrium must undergo a physiological transformation called decidualization. These changes encompass the remodeling of endometrial immune cells leading to immunotolerance of...

A hallmark of Parkinson’s disease (PD) is the formation of Lewy bodies in the brain. Lewy bodies are rich in the aggregated form of misfolded α-Synuclein (α-Syn). The brain from PD patients can only be analyzed after postmortem, therefore, limiting the diagnosis of PD to the manifestation of motor symptoms. In PD patients and animal models, phospho...

The SARS-CoV-2 virus is the causative agent of the global COVID-19 infectious disease outbreak, which can lead to acute respiratory distress syndrome (ARDS). However, it is still unclear how the virus interferes with immune cell and metabolic functions in the human body. In this study, we investigated the immune response in acute or convalescent CO...

A hallmark of Parkinson' disease (PD) is the formation of Lewy bodies in the brain. Lewy bodies are rich in the aggregated form of misfolded α–Synuclein (α–Syn). The brain from PD patients can only be analysed after post–mortem, limiting the diagnosis of PD to the manifestation of motor symptoms. In PD patients and animal models phosphorylated α–Sy...

Polyphenol compounds found in green tea have a great therapeutic potential to influence multiple human diseases including malignancy and inflammation. In this mini review, we describe effects of green tea and the most important component EGCG in malignancy and inflammation. We focus on cellular mechanisms involved in the modification of T cell func...

The consumption of dairy products, particularly of low fat milk, has been shown to be associated with the occurrence of Parkinson's disease. This association does not necessarily reflect a pathophysiological role of milk intake in the development of Parkinson's disease. Nevertheless, the present review discusses a potential mechanism possibly media...

Since Braak’s hypothesis stating that sporadic Parkinson’s disease follows a specific progression of the pathology from the peripheral to the central nervous system and can be monitored by detecting accumulation of the alpha-Synuclein protein. There is growing interest in understanding how the gut (commensal) microbiome can regulate alpha-Synuclein...

The serum- and glucocorticoid-inducible kinase 1 (SGK1) is subject to genetic up-regulation by diverse stimulators including glucocorticoids, mineralocorticoids, dehydration, ischemia, radiation and hyperosmotic shock. To become active, the expressed kinase requires phosphorylation, which is accomplished by PI3K/PDK1 and mTOR dependent signaling. S...

Abstract The proper communication between gut and brain is pivotal for the maintenance of health and, dysregulation of the gut-brain axis can lead to several clinical disorders. In Parkinson’s disease (PD) 85% of all patients experienced constipation many years before showing any signs of motor phenotypes. For differential diagnosis and preventive...

The SARS-CoV-2 virus is the causative agent of the global COVID-19 infectious disease outbreak, which can lead to acute respiratory distress syndrome (ARDS). However, it is still unclear how the virus interferes with immune cell and metabolic functions in the human body. In this study, we investigated the immune response in 10 acute or convalescent...

Glucose uptake into lymphocytes is accomplished by non-concentrative glucose carriers of the GLUT family (GLUT1, GLUT3, GLUT4, GLUT6) and/or by the Na+-coupled glucose carrier SGLT1. The latter accumulates glucose against glucose gradients and is still effective at very low extracellular glucose concentrations. Signaling involved in SGLT1 expressio...

Rapid and frequent screening of cytokines as immunomodulation agents is necessary for precise interventions in severe pathophysiological conditions. In addition to high-sensitivity detection of such analytes in complex biological fluids such as blood, saliva, and cell culture medium samples, it is also crucial to work out miniaturized bioanalytical...

LEFTY2 (endometrial bleeding associated factor; EBAF or LEFTYA), a cytokine released shortly before menstrual bleeding, is a negative regulator of cell proliferation and tumour growth. LEFTY2 down-regulates Na⁺/H⁺ exchanger activity with subsequent inhibition of glycolytic flux and lactate production in endometrial cancer cells. Glucose can be util...

Scope: Urolithin A (UA) is a gut-derived metabolite from ellagic acid found in pomegranates, berries and nuts can down-regulate cell proliferation and migration. Cell proliferation and cell motility require actin reorganization which is under control of ras-related C3 botulinum toxin substrate 1 (Rac1) and p21 protein-activated kinase 1 (PAK1). Th...

The proper communication between gut and brain is pivotal for the maintenance of health and dysregulation of the gut brain axis can lead to several clinical disorders. Also, in Parkinson's disease (PD) 85 percentage of all patients experienced constipation long before showing any signs of motor phenotypes. For differential diagnosis and when it com...

The gut microbiota influences several biological functions including immune responses. Inflammatory bowel disease is favorably influenced by consumption of several dietary natural plant products such as pomegranate, walnuts, and berries containing polyphenolic compounds such as ellagitannins and ellagic acid. The gut microbiota metabolizes ellagic...

The transcription factor p53 suppresses tumor growth by inducing nucleated cell apoptosis and cycle arrest. Because of its influence on primitive erythroid cell differentiation and survival, p53 is an important determinant of erythropoiesis. However, the impact of p53 on the fate of erythrocytes, cells lacking nucleus and mitochondria, during their...

Early embryo development and endometrial differentiation are initially independent processes, and synchronization, imposed by a limited window of implantation, is critical for reproductive success. A putative negative regulator of endometrial receptivity is LEFTY2, a member of the transforming growth factor (TGF)-β family. LEFTY2 is highly expresse...

35 36 The gut microbiota influences several biological functions including immune response. 37 Inflammatory bowel disease is favourably influenced by consumption of several dietary natural plant 38 products such as pomegranate, walnuts and berries containing polyphenolic compounds such as 39 ellagitannins and ellagic acid. The gut microbiota metabo...

Scientific Reports Loss of Endometrial Sodium Glucose Cotransporter SGLT1 is Detrimental to Embryo Survival and Fetal Growth in Pregnancy Close menuClose menuClose menuClose menu More detail Article | OPEN Loss of Endometrial Sodium Glucose Cotransporter SGLT1 is Detrimental to Embryo Survival and Fetal Growth in Pregnancy Madhuri S. Salker, Yoges...

The cause of death among the majority of endometrial cancer patients involves migration of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into neighbouring organs. It is, thereby, important to identify factors that mediate metastasis. Cell adhesion and migration are modified by the mesenchymal stem cell (M...

Knockdown of SUSD2 decreased LGALS1 and MKi67 transcript levels in Ishikawa cells. (A) Arithmetic means ± SEM (n = 4) of LGALS1 normalized to L19 transcript levels in Ishikawa cells. (B) Arithmetic means ± SEM (n = 4) MKi67 transcript levels normalized to L19 transcript levels in Ishikawa cells. Data of both graphs are depicted as fold induction re...

Titration and Time-course of the TGFβ effect on SUSD2+ Ishikawa cells. (A) Arithmetic means ± SEM (n = 3) of the fold change of SUSD2+ expressing Ishikawa cells. Bar graph showing the effect of increasing TGFβ concentrations (1, 5, 10, 20, 50 ng/ml) for 72h Data are depicted as fold induction relative to untreated (Control) samples. *P< 0.05, **P<0...

CD4+ T cells are key elements in immune responses and in ammation. Activation of T cell receptors in CD4+ T cells triggers cytosolic Ca2+ release with subsequent store operated Ca2+ entry (SOCE), which is accomplished by the pore forming Ca2+ release activated Ca2+ (CRAC) channel Orai1 and its regulator stromal cell-interaction molecule 2 (STIM2)....

Background: MicroRNAs (miRNAs) negatively regulate gene expression at a post-transcriptional level. Dicer, a cytoplasmic RNase III enzyme, is required for the maturation of miRNAs from precursor miRNAs. Dicer, therefore, is a critical enzyme involved in the biogenesis and processing of miRNAs. Several biological processes are controlled by miRNAs,...

Background: Cellular glucose uptake may involve either non-concentrative glucose carriers of the GLUT family or Na+-coupled glucose-carrier SGLT1, which accumulates glucose against glucose gradients and may thus accomplish cellular glucose uptake even at dramatically decreased extracellular glucose concentrations. SGLT1 is not only expressed in ep...

Background/aims: Key properties of tumor cells include enhanced glycolytic flux with excessive consumption of glucose and formation of lactate. As glycolysis is highly sensitive to cytosolic pH, maintenance of glycolysis requires export of H+ ions, which is in part accomplished by Na+/H+ exchangers, such as NHE1. The carrier is sensitive to oxidat...

Background/aims: Tumor cell proliferation is modified by 1,25-Dihydroxy-Vitamin D3 (1,25(OH)2D3), a steroid hormone predominantly known for its role in calcium and phosphorus metabolism. Key properties of tumor cells include enhanced glycolytic flux with excessive consumption of glucose and formation of lactate. As glycolysis is highly sensitive t...

Background/aims: Uterine rudiments from patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) contain all tissues typically found in the uterus. Endometrium from the rudiments predominantly exhibits basalis-like features, and endometrial proliferative capacity in patients' epithelium and stroma is significantly lower. Methods: This singl...

Background/aims: β-Klotho, a transmembrane protein expressed in several tissues including the brain and the kidney, is critically important for inhibition of 1,25(OH)2D3 formation by FGF23. The extracellular domain of Klotho protein could be cleaved off, thus being released into blood or cerebrospinal fluid. Soluble klotho is a β-glucuronidase par...

Background: Cell proliferation and motility require actin reorganization, which is under control of various signalling pathways including ras-related C3 botulinum toxin substrate 1 (RAC1), p21 protein-activated kinase 1 (PAK1) and actin related protein 2 (ARP2). Tumour cell proliferation is modified by 1α,25-Dihydroxy-Vitamin D3 (1α,25(OH)2D3), a...

Background: Serum & Glucocorticoid Regulated Kinase 1 (SGK1) plays a fundamental role in ion and solute transport processes in epithelia. In the endometrium, down-regulation of SGK1 during the window of receptivity facilitates embryo implantation whereas expression of a constitutively active mutant in the murine uterus blocks implantation. Method...

Background: Serum & Glucocorticoid Regulated Kinase 1 (SGK1) plays a fundamental role in ion and solute transport processes in epithelia. In the endometrium, down-regulation of SGK1 during the window of receptivity facilitates embryo implantation whereas expression of a constitutively active mutant in the murine uterus blocks implantation. Methods/...

CD4+ T helper 9 (Th9) cells are a newly discovered Th cell subset that produce the pleiotropic cytokine IL-9. Th9 cells can protect against tumours and provide resistance against helminth infections. Given their pivotal role in the adaptive immune system, understanding Th9 cell development and the regulation of IL-9 production could open novel immu...

Background/aims: Activation of T cell receptors (TCRs) in CD4+ T cells leads to a cascade of signalling reactions including increase of intracellular calcium (Ca2+) levels with subsequent Ca2+ dependent stimulation of gene expression, proliferation, cell motility and cytokine release. The increase of cytosolic Ca2+ results from intracellular Ca2+...

Background: Serum & glucocorticoid inducible kinase (SGK1) regulates several ion channels, including amiloride sensitive epithelial Na+ channel (ENaC). SGK1 and ENaC in the luminal endometrium epithelium, are critically involved in embryo implantation, although little is known about their regulation. The present study explored whether SGK1 and ENa...

Background: LEFTY2, a suppressor of cell proliferation, tumor growth, regulator of stemness and embryonic differentiation, is a negative regulator of cancer cell reprogramming. Malignant transformation may lead to migration requiring loss of adhesion and gain of migratory activity. Signaling involved in the orchestration of migration, proliferatio...

DJ-1/Park7 is a redox-sensitive chaperone protein counteracting oxidation and presumably contributing to the control of oxidative stress responses and thus inflammation. DJ-1 gene deletion exacerbates the progression of Parkinson's disease presumably by augmenting oxidative stress. Formation of reactive oxygen species (ROS) is paralleled by activat...

Background/aims: Regulatory T cell (Treg) is required for the maintenance of tolerance to various tissue antigens and to protect the host from autoimmune disorders. However, Treg may, indirectly, support cancer progression and bacterial infections. Therefore, a balance of Treg function is pivotal for adequate immune responses. Acid sphingomyelinas...

LeftyA, a cytokine regulating stemness and embryonic differentiation, down-regulates cell proliferation and migration. Cell proliferation and motility require actin reorganization, which is under control of ras-related C3 botulinum toxin substrate 1 (Rac1) and p21 protein-activated kinase 1 (PAK1). The present study explored whether LeftyA modifies...

Regulatory T cells (Tregs) are required for effective immune homeostasis by suppressing harmful immune responses against self-antigens. Transcription factor Foxp3 is required for the development of these cells. How Foxp3 is stabilised and affects Tregs development is still incompletely understood. Previous studies have suggested that hypoxia induci...

Parkinson's-associated protein DJ-1/Park7, is a key regulator of redox signalling in neurons and muscles by regulating reactive oxygen species (ROS) production. Defects in DJ-1 are suggested to cause autosomal recessive early-onset Parkinson's disease. Further, deregulated DJ-1 signalling has now been ascribed to other pathologies including diabete...

Fibroblast growth factor (FGF23) plasma levels are elevated in cardiac and renal failure and correlate with poor clinical prognosis of those disorders. Both disorders are associated with inflammation and activation of the inflammatory transcription factor NFκB. An excessive FGF23 level is further observed in Klotho-deficient mice. The present study...

The fibroblast growth factor (FGF23) plasma level is high in cardiac and renal failure and is associated with poor clinical prognosis of these disorders. Both diseases are paralleled with hyperaldosteronism. Excessive FGF23 levels and hyperaldosteronism are further observed in Klotho-deficient mice. The present study explored a putative aldosterone...

Background/aims: Lithium, a widely used drug for the treatment of mood disorders, has previously been shown to stimulate the release of fibroblast growth factor FGF23, a powerful regulator of 1,25(OH)2D3 formation and mineral metabolism. The cellular mechanisms involved have remained elusive. Lithium has been shown to modify Ca2+ signaling. In a w...

Regulatory T cells (Tregs) are essential for maintaining an effective immune tolerance and a homeostatic balance of various other immune cells. To manipulate the immune response during infections and autoimmune disorders, it is essential to know which genes or key molecules are involved in the development of Tregs. Transcription factor Foxp3 is req...

The mitogen- and stress-activated kinase MSK1/2 plays a decisive role in apoptosis. In analogy to apoptosis of nucleated cells, suicidal erythrocyte death called eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine (PS) externalization. Here, we explored whether MSK1/2 participates in the regulatio...

Kinases involved in the regulation of epithelial transport include SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1). SPAK and OSR1 are both regulated by WNK (with-no-K(Lys)) kinases. The present study explored whether SPAK and/or OSR1 influence the excitatory amino acid transporter EAAT3, which accompl...

The WNK-dependent STE20/SPS1-related proline/alanine-rich kinase SPAK participates in the regulation of NaCl and Na(+),K(+),2Cl(-) cotransport and thus renal salt excretion. The present study explored whether SPAK has similarly the potential to regulate the epithelial Na(+) channel (ENaC). ENaC was expressed in Xenopus oocytes with or without addit...

Anemia, a common condition in the elderly, could result from impaired formation and/or from accelerated loss of circulating erythrocytes. The latter could result from premature suicidal erythrocyte death or eryptosis characterized by phosphatidylserine (PS) exposure at the erythrocyte surface. Triggers of eryptosis include increased cytosolic Ca(2+...

LeftyA, a powerful regulator of stemness, embryonic differentiation, and reprogramming of cancer cells, counteracts cell proliferation and tumor growth. Key properties of tumor cells include enhanced glycolytic flux, which is highly sensitive to cytosolic pH and thus requires export of H(+) and lactate. H(+) extrusion is in part accomplished by Na(...

Background/aims: SPAK (STE20-related proline/alanine-rich kinase) is a powerful regulator of renal tubular ion transport and blood pressure. Moreover, SPAK contributes to the regulation of cell volume. Little is known, however, about a role of SPAK in the regulation or organic solutes. The present study thus addressed the influence of SPAK on the...

Human embryos frequently harbor large-scale complex chromosomal errors that impede normal development. Affected embryos may fail to implant although many first breach the endometrial epithelium and embed in the decidualizing stroma before being rejected via mechanisms that are poorly understood. Here we show that developmentally impaired human embr...

Reproduction in humans is unique in two major aspects. First, the incidence of chromosomally abnormal and developmentally compromised human preimplantation embryos is exceptionally high, and second, the uterus decidualizes spontaneously each cycle, a process also responsible for the menstrual shedding of the endometrium in the absence of pregnancy....

Reproduction in humans is unique in two major aspects. First, the incidence of chromosomally abnormal and developmentally compromised human preimplantation embryos is exceptionally high, and second, the uterus decidualizes spontaneously each cycle, a process also responsible for the menstrual shedding of the endometrium in the absence of pregnancy....

The actions of glucocorticoids at the feto-maternal interface are not well understood. Here, we show that decidualization of human endometrial stromal cells (HESCs) in response to progesterone and cAMP signaling is associated with a strong induction of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) expression and enzyme activity. Decidualization...

Decidualization renders the endometrium transiently receptive to an implanting blastocyst although the underlying mechanisms remain incompletely understood. Here we show that human endometrial stromal cells (HESCs) rapidly release IL-33, a key regulator of innate immune responses, upon decidualization. In parallel, differentiating HESCs upregulate...

Decidualization renders the endometrium transiently receptive to an implanting blastocyst although the underlying mechanisms remain incompletely understood. Here we show that human endometrial stromal cells (HESCs) rapidly release IL-33, a key regulator of innate immune responses, upon decidualization. In parallel, differentiating HESCs upregulate...

Il-33 knockdown in HESCs decidualized for 2 days triggers an inflammatory response akin to that seen in cells decidualized for 8 days. (A) Number of transcripts significantly up- or down-regulated in each of the indicated categories upon decidualization for 2 or 8 days (D2 and D8, respectively) compared to undifferentiated cells. (B) Number of tran...

Schematic representation. ST2 primer pairs used to amplify all Total-ST2 transcripts (T-ST2) or the transmembrane ST2L (TM-ST2) transcripts. (TIFF)