Associate Professor Pradeep Tanwar
NHMRC Career Development Fellow
School of Biomedical Sciences and Pharmacy (Medical Biochemistry)
- Phone:(02) 4921 5148
Tackling Silent Killers
By investigating the pathogenesis of female reproductive tract cancers, Dr Pradeep Tanwar aims to develop targeted therapies to improve clinical outcomes.
Dr Pradeep Tanwar and his team are methodically investigating questions surrounding female reproductive tract cancers from several different angles.
An investigator of the Hunter Cancer Research Alliance, the potential massive impact of Pradeep’s work has been recognized by his appointment as an ARC Future Fellow and a Cancer Institute NSW Career Development Fellow.
“We work on female reproductive tract cancers,” Pradeep explains.
“We mainly focus on two cancers - ovarian cancer, the most deadly of gynecological cancers in women, and endometrial cancer or cancer of the uterus, which is the most common gynecological cancer in females.”
“What we are interested in is how the cancer develops to start with, and once it has developed, how does it progress to a stage where it spreads to other organs,” he says.
“And when it spreads, how can we control it. So we are interested in both how we can control the development or initiation, and how we can control the spread, of these cancers.”
A needle in a haystack
Pradeep explains that genetics, lifestyle factors, and age, are all risk factors for reproductive tract cancers.
“But having a genetic predisposition does not mean these cancers will develop, so lifestyle factors play a role”, Pradeep explains.
“You will find two thousand factors that are different between a patient that has cancer and a patient who does not have cancer, a patient who has metastasis versus a patient who does not have it.”
“So, what are those differences? What combination of factors result in the actual development of the disease? We are looking for a needle in a haystack. But that might be the key.”
Breakdown in cell communication has been identified as a factor in increased incidence of cancers as has been patient’s age, so this communication process is also being studied.
“Cancer is basically excessive production of cell types,” Pradeep says.
“Every day billions of cells are regenerated in the body, and a number of cells need to die to keep everything in perfect harmony. The signals that keep this system in harmony are sometimes disrupted. We hope to discover a way to correct that disruption.”
With lack of population-wide screening program, symptoms that can mimic other conditions, and diagnostic procedures that are difficult and non-conclusive, cancers of the reproductive tract are notoriously illusive and are most often diagnosed in later stages.
Pradeep’s group use genetically modified animal models, cancer patient-derived xenograft models and primary human tissue samples to define the molecular and cellular events involved in carcinogenesis.
The Hunter Cancer Biobank (HCB) at the Hunter Medical Research Institute (HMRI) collects affected patient tissue, which is then provided to researchers. In this important way, many cancer patients through the Hunter and surrounding areas have contributed to this and other cancer research.
Utilising animal models allows researchers to target early stages of the disease and investigate possible markers that may be identified through existing pathology test processes, ultimately facilitating more timely diagnosis.
Working with these models also allows the team in the lab to bombard tumorous tissue with combinations of off-label medications. Pradeep is hoping to find a medication, already approved and mass produced, or combination of such, that can be repurposed to aid in the fight against these cancers.
Working with a former Harvard colleague, Pradeep has already made a major breakthrough in identifying a protein that can act as a tumour suppressor when treating chemo-resistant ovarian cancer.
He has recently published a paper showing that in animal models and human ovarian cancer cells, progesterone suppresses and oestrogen promotes the growth of cancer cells.
“We were able to find that the initial lesions of ovarian cancers had receptors for oestrogen and progesterone. So if you have too much estrogen, those lesions will develop into cancer.”
As a result of this work, his team including clinicians are exploring the use of hormonal treatments in combination with chemotherapy for reproductive tracts cancers.
“The incidence of cancer in patients is much higher for those who have never used oral contraception than in patients who have used oral contraception,” Pradeep asserts.
“If you take the Pill it suppresses your ovaries and you are less likely to develop ovarian cancer, all reproductive tract cancers.”
“This is vital information for women who may be at high risk due to family history, and women who are postponing pregnancies until later in life.”
The path to here
Pradeep is originally trained in veterinary medicine and animals first ignited his passion for discovering disease prevention strategies.
Frustrated by the amount of animals being put down due to prohibitive treatment costs, Pradeep reasoned that facilitating the maintenance of animal health and worth removed the necessity for large treatment costs, long recovery periods or euthanasia.
“One of the things I also learnt as a veterinarian is that the underlying principle of animal domestication seems to be production. Without reproduction, there is no production. If a cow is not breeding, a farmer is going to get rid of her.”
This principle lead Pradeep to become invested in the study of reproductive systems. A PhD at the University of New England furthered his study of this system in women. A post-doctoral stint at Harvard followed.
“At Harvard, you are embedded in a hospital, so you have oncologists, surgeons, gynecologists, obstetricians, and researchers, all having lunch at the same time,” Pradeep recalls.
“They were discussing their patients and we were discussing our research. I became more and more interested in ovarian and uterine cancers, and learnt a great deal.”
These experiences have resulted in Pradeep establishing a lab environment which comprises of both systemic and specialized approaches in addressing a research problem. Pradeep’s lab also addresses fundamental questions regarding the normal functioning of the female reproductive tract, such as the cellular dynamics. Often answers to these questions helps in understanding what is going wrong with the system leading to disease development.
When reflecting on the many challenges to the diagnosis and treatment of female reproductive cancers, Pradeep cites the increased incidence of obesity amongst women as a major hurdle.
Pradeep and his team have spent four years investigating the role of fat cells in the growth of cancer cells. By providing accessible fuel, fat deposits in the body can accelerate and feed cancers. This process is particularly relevant to ovarian cancer, which metastasizes first to the omentum (a fatty tissue).
“These cancer cells have free food and a free supply of energy,” Pradeep explains.
“But if we can find ways to destruct that communication, then it is possible that cancer cells might be starved to death.”
Another challenge is translating research directly into practice, with Pradeep seeing opportunities for women, and their clinicians, to make informed female reproductive health choices but lacking the information to do so.
“Female reproductive health and fitness is still a taboo topic, although it is a very important part of female biology, and essential to women's health and survival,” Pradeep says.
“So not only do we need to continue searching for answers regarding these cancers, but we need to raise awareness about what we find which translates directly to saving lives.”
Associate Professor Pradeep Tanwar is an NHMRC Career Development Fellow. Throughout his research career,
1. Role of Microenvironment in Endometrial cancer 2. Wnt-PI3K-mTOR signaling axis, EMT (
Course coordinator for HUBS2107: Mammalian Growth and Development
- Cancer biology
- Cancer stem cells
- Endometrial cancer
- Genitourinary cancers
- Gynecologic oncology
- ovarian cancer
- English (Fluent)
Fields of Research
|060403||Developmental Genetics (incl. Sex Determination)||20|
|111201||Cancer Cell Biology||50|
|Title||Organisation / Department|
|Associate Professor||University of Newcastle
School of Biomedical Sciences and Pharmacy
|Dates||Title||Organisation / Department|
|1/08/2012 - 13/12/2014||Lecturer||University of Newcastle
School of Biomedical Sciences and Pharmacy
For publications that are currently unpublished or in-press, details are shown in italics.
Journal article (43 outputs)
Jamaluddin MFB, Nagendra PB, Nahar P, Oldmeadow C, Tanwar PS, 'Proteomic Analysis Identifies Tenascin-C Expression Is Upregulated in Uterine Fibroids.', Reproductive sciences (Thousand Oaks, Calif.), 26 476-486 (2019)
Brown Y, Hua S, Tanwar PS, 'Extracellular matrix-mediated regulation of cancer stem cells and chemoresistance', International Journal of Biochemistry and Cell Biology, 109 90-104 (2019) [C1]
© 2019 Elsevier Ltd The identity of cancer stem cells (CSCs) remains an enigma, with the question outstanding of whether CSCs are fixed entities or plastic cell states in response... [more]
© 2019 Elsevier Ltd The identity of cancer stem cells (CSCs) remains an enigma, with the question outstanding of whether CSCs are fixed entities or plastic cell states in response to microenvironmental cues. Recent evidence highlights the power of the tumor microenvironment to dictate CSC functionality and spatiotemporal regulation that gives rise to tumor heterogeneity. This microenvironmental regulation of CSCs parallels that of normal tissues, whereby resident stem cells reside within specialized microenvironments or ¿niches¿, which provide the cellular and molecular signals that wire every aspect of stem cell behavior and fate. The extracellular matrix (ECM), along with its sequestered growth factors, is a fundamental component of the stem cell niche. Pathological ECM remodeling is an established hallmark of cancer, with the ECM a key mediator of metastasis and drug resistance. In this review, we discuss the controversial identity of CSCs and new understanding of the impact of tumor microenvironment on CSC function and phenotype. We outline parallels between development, wound repair and cancer to discuss how changes in ECM dynamics influence stem cell function during normal physiological processes and pathological states, as well as the transition between the two in the form of precancerous lesions. We then explore examples illustrating the molecular circuits partnering cancer cells with stromal cells and how this communication involving ECM imparts a CSC phenotype and promotes chemoresistance. Understanding the mechanisms underlying CSC functionality and chemoresistance, along with mathematical modeling approaches and advancing technologies for targeting the undruggable proteome, should open opportunities for cancer breakthroughs in the future.
Al-Juboori AAA, Ghosh A, Jamaluddin MFB, Kumar M, Sahoo SS, Syed SM, et al., 'Proteomic Analysis of Stromal and Epithelial Cell Communications in Human Endometrial Cancer Using a Unique 3D Co-Culture Model.', Proteomics, e1800448 (2019)
Goad J, Ko Y-A, Kumar M, Jamaluddin MFB, Tanwar PS, 'Oestrogen fuels the growth of endometrial hyperplastic lesions initiated by overactive Wnt/ß-catenin signalling.', Carcinogenesis, 39 1105-1116 (2018) [C1]
Sahoo SS, Lombard JM, Ius Y, O'Sullivan R, Wood LG, Nahar P, et al., 'Adipose-Derived VEGF¿mTOR Signaling Promotes Endometrial Hyperplasia and Cancer: Implications for Obese Women', Molecular Cancer Research, 16 309-321 (2018) [C1]
2017 American Association for Cancer Research. Obesity is responsible for increased morbidity and mortality in endometrial cancer. Despite the positive correlation of body mass in... [more]
2017 American Association for Cancer Research. Obesity is responsible for increased morbidity and mortality in endometrial cancer. Despite the positive correlation of body mass index (BMI) or obesity in endometrial carcinogenesis, the contribution of adipose tissue to the pathogenesis of endometrial hyperplasia and cancer is unclear. This study clarifies the role of adipocytes in the pathogenesis of endometrial cancer by demonstrating that adipocyte-conditioned medium (ACM) increases proliferation, migration, and survival of endometrial cancer cells compared with preadipocyte-conditioned medium (PACM). Comparative cytokine array analysis of ACM and PACM reveal upregulation of a group of cytokines belonging to the VEGF signaling pathway in ACM. VEGF protein expression is upregulated in visceral adipose tissue (VAT) in obese patients, which is correlated with increased tumor growth in an in vivo xenograft model. The increased tumor size is mechanistically associated with the activation of the PI3K/AKT/mTOR pathway, a downstream target of VEGF signaling, and its suppression decreased the growth-promoting effects of VAT on endometrial cancer cells. Similar to the human model systems, pathologic changes in endometrial cells in a hyperphagic obese mouse model are associated with increased body weight and hyperactive mTOR signaling. Analysis of human tissue specimens depicts increased in tumor vasculature and VEGF-mTOR activity in obese endometrial cancer patients compared with nonobese patients. Collectively, these results provide evidence that VEGF-mTOR signaling drives endometrial cell growth leading to hyperplasia and cancer. Implications: Adipocyte-derived VEGF¿mTOR signaling may be an attractive therapeutic target against endometrial cancer in obese women.
Ko YA, Jamaluddin MFB, Adebayo M, Bajwa P, Scott RJ, Dharmarajan AM, et al., 'Extracellular matrix (ECM) activates ß-catenin signaling in uterine fibroids', Reproduction, 155 61-71 (2018) [C1]
© 2018 Society for Reproduction and Fertility. Recent studies showed that genetic aberrations in the MED12 gene, probably through the canonical WNT/ß-catenin pathway, lead to the ... [more]
© 2018 Society for Reproduction and Fertility. Recent studies showed that genetic aberrations in the MED12 gene, probably through the canonical WNT/ß-catenin pathway, lead to the pathogenesis of uterine fibroids. However, a comprehensive analysis of the WNT pathway in MED12-mutated and MED12-wildtype fibroids has not been performed. The objective of this study was to determine the status of the WNT pathway in human fibroids. We performed Sanger sequencing to define the MED12 mutational status of fibroids and normal myometrium samples. qPCR arrays were carried out to determine the status of the WNT signaling pathway in MED12-mutated and MED12-wild-type fibroids. Liquid chromatography-mass spectrometry (LC-MS), Western blotting and immunohistochemistry were used to monitor the expression of ß-catenin. We showed that ß-catenin expression was increased in fibroids compared to the adjacent myometrium samples. However, ß-catenin expression showed no correlation with MED12 mutation status. Of all the WNT signaling components, WNT inhibitors showed the greatest differences in expression between fibroids and controls. WIF1, a WNT inhibitor, was identified as the most significantly upregulated gene in fibroids. We cultured primary fibroid cells on hydrogels of known stiffness to decipher the influence of biomechanical cues on ß-catenin expression and revealed increased levels of ß-catenin when cells were cultured on a stiffer surface. In conclusion, our data showed that ß-catenin expression in fibroids occurs independently of MED12 mutations. Biomechanical changes upregulate ß-catenin expression in fibroids, providing an attractive avenue for developing new treatments for this disease.
Jamaluddin MFB, Nahar P, Tanwar PS, 'Proteomic characterization of the extracellular matrix of human uterine fibroids', Endocrinology, 159 2656-2669 (2018) [C1]
© 2018 Endocrine Society. Uterine leiomyomas (fibroids) are the most common benign tumors that are associated with increased production of extracellular matrix (ECM). Excessive EC... [more]
© 2018 Endocrine Society. Uterine leiomyomas (fibroids) are the most common benign tumors that are associated with increased production of extracellular matrix (ECM). Excessive ECM deposition plays a major role in the enlargement and stiffness of these tumors and contributes to clinical symptoms, such as abnormal bleeding and abdominal pain. However, no study so far has explored the global composition of the ECM of fibroids and normal myometrium. In this study, we performed a systematic ECM enrichment procedure and comparative proteomic analyses to profile the ECM composition of genetically annotated different-sized fibroids (small, medium, and large) and adjacent normal myometrium (ANM). Our matrisome analysis identified a combined total of 108, 126, 126, and 130 unique ECM and ECM-associated proteins with a confidence corresponding to a false discovery rate,1%inANM and in small, medium, and large fibroids, respectively. The majority of fibroid ECM proteins belong to the core matrisome that includes glycoproteins, collagens, and proteoglycans. Considering that the small-sized fibroids represent the initial stages of leiomyogenesis, we highlighted some of the most abundant and important upregulated ECM proteins in small fibroids (i.e., POSTN, TNC, COL3A1, COL24A1, and ASPN). Furthermore, we revealed 30 unique ECM proteins that exist only in fibroids but that are not present in ANM regardless of MED12 mutation. We propose that some of the proteins identified represent potential novel ECM drug targets that may change the paradigm of fibroid treatment.
Sahoo SS, Zhang XD, Hondermarck H, Tanwar PS, 'The Emerging Role of the Microenvironment in Endometrial Cancer', CANCERS, 10 (2018) [C1]
Jamaluddin MFB, Ko YA, Kumar M, Brown Y, Bajwa P, Nagendra PB, et al., 'Proteomic profiling of human uterine fibroids reveals upregulation of the extracellular matrix protein periostin', Endocrinology, 159 1106-1118 (2018) [C1]
Copyright © 2018 Endocrine Society The central characteristic of uterine fibroids is excessive deposition of extracellular matrix (ECM), which contributes to fibroid growth and bu... [more]
Copyright © 2018 Endocrine Society The central characteristic of uterine fibroids is excessive deposition of extracellular matrix (ECM), which contributes to fibroid growth and bulk-type symptoms. Despite this, very little is known about patterns of ECM protein expression in fibroids and whether these are influenced by the most common genetic anomalies, which relate to MED12. We performed extensive genetic and proteomic analyses of clinically annotated fibroids and adjacent normal myometrium to identify the composition and expression patterns of ECM proteins in MED12 mutation-positive and mutation-negative uterine fibroids. Genetic sequencing of tissue samples revealed MED12 alterations in 39 of 65 fibroids (60%) from 14 patients. Using isobaric tagged-based quantitative mass spectrometry on three selected patients (n = 9 fibroids), we observed a common set of upregulated (.1.5-fold) and downregulated (,0.66-fold) proteins in small, medium, and large fibroid samples of annotated MED12 status. These two sets of upregulated and downregulated proteins were the same in all patients, regardless of variations in fibroid size and MED12 status. We then focused on one of the significant upregulated ECM proteins and confirmed the differential expression of periostin using western blotting and immunohistochemical analysis. Our study defined the proteome of uterine fibroids and identified that increased ECM protein expression, in particular periostin, is a hallmark of uterine fibroids regardless of MED12 mutation status. This study sets the foundation for further investigations to analyze the mechanisms regulating ECM overexpression and the functional role of upregulated ECM proteins in leiomyogenesis.
George JW, Patterson AL, Tanwar PS, Kajdacsy-Balla A, Prins GS, Teixeira JM, 'Specific deletion of LKB1/Stk11 in the Müllerian duct mesenchyme drives hyperplasia of the periurethral stroma and tumorigenesis in male mice', Proceedings of the National Academy of Sciences of the United States of America, 114 3445-3450 (2017) [C1]
Kumar M, Tanwar PS, 'Canonical Wnt/ß-catenin signaling regulates postnatal mouse epididymal development but does not affect epithelial cell differentiation.', Endocrinology, 158 4286-4299 (2017) [C1]
Sahoo SS, Quah MY, Nielsen S, Atkins J, Au GG, Cairns MJ, et al., 'Inhibition of extracellular matrix mediated TGF-ß signalling suppresses endometrial cancer metastasis.', Oncotarget, 8 (2017) [C1]
Goad J, Ko YA, Kumar M, Syed SM, Tanwar PS, 'Differential Wnt signaling activity limits epithelial gland development to the anti-mesometrial side of the mouse uterus', Developmental Biology, 423 138-151 (2017) [C1]
Ghosh A, Syed SM, Tanwar PS, 'In vivo genetic cell lineage tracing reveals that oviductal secretory cells self-renew and give rise to ciliated cells', Development (Cambridge), 144 3031-3041 (2017) [C1]
© 2017. Published by The Company of Biologists Ltd. The epithelial lining of the fallopian tube is vital for fertility, providing nutrition to gametes and facilitating their trans... [more]
© 2017. Published by The Company of Biologists Ltd. The epithelial lining of the fallopian tube is vital for fertility, providing nutrition to gametes and facilitating their transport. It is composed of two major cell types: secretory cells and ciliated cells. Interestingly, human ovarian cancer precursor lesions primarily consist of secretory cells. It is unclear why secretory cells are the dominant cell type in these lesions. Additionally, the underlying mechanisms governing fallopian tube epithelial homoeostasis are unknown. In the present study, we showed that across the different developmental stages of mouse oviduct, secretory cells are the most frequently dividing cells of the oviductal epithelium. In vivo genetic cell lineage tracing showed that secretory cells not only self-renew, but also give rise to ciliated cells. Analysis of a Wnt reporter mouse model and various Wnt target genes showed that the Wnt signaling pathway is involved in oviductal epithelial homoeostasis. By developing two triple-transgenic mouse models, we showed that Wnt/ ß-catenin signaling is essential for self-renewal as well as the differentiation of secretory cells. In summary, our results provide mechanistic insight into oviductal epithelial homoeostasis.
Kumar M, Tanwar P, 'Organ Culture and Whole Mount Immunofluorescence Staining of Mouse Wolffian Ducts', JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, (2017) [C1]
Bajwa P, Nielsen S, Lombard JM, Rassam L, Nahar P, Rueda BR, et al., 'Overactive mTOR signaling leads to endometrial hyperplasia in aged women and mice', Oncotarget, 8 7265-7275 (2017) [C1]
Kumar M, Atkins J, Cairns M, Ali A, Tanwar PS, 'Germ cell-specific sustained activation of Wnt signalling perturbs spermatogenesis in aged mice, Possibly through non-coding RNAs', Oncotarget, 7 85709-85727 (2016) [C1]
Dysregulated Wnt signalling is associated with human infertility and testicular cancer. However, the role of Wnt signalling in male germ cells remains poorly understood. In this s... [more]
Dysregulated Wnt signalling is associated with human infertility and testicular cancer. However, the role of Wnt signalling in male germ cells remains poorly understood. In this study, we first confirmed the activity of Wnt signalling in mouse, dog and human testes. To determine the physiological importance of the Wnt pathway, we developed a mouse model with germ cell-specific constitutive activation of ßcatenin. In young mutants, similar to controls, germ cell development was normal. However, with age, mutant testes showed defective spermatogenesis, progressive germ cell loss, and flawed meiotic entry of spermatogonial cells. Flow sorting confirmed reduced germ cell populations at the leptotene/zygotene stages of meiosis in mutant group. Using thymidine analogues-based DNA double labelling technique, we further established decline in germ cell proliferation and differentiation. Overactivation of Wnt/ßcatenin signalling in a spermatogonial cell line resulted in reduced cell proliferation, viability and colony formation. RNA sequencing analysis of testes revealed significant alterations in the non-coding regions of mutant mouse genome. One of the novel non-coding RNAs was switched on in mutant testes compared to controls. QPCR analysis confirmed upregulation of this unique noncoding RNA in mutant testis. In summary, our results highlight the significance of Wnt signalling in male germ cells.
Nagendra PB, Goad J, Nielsen S, Rassam L, Lombard JM, Nahar P, Tanwar PS, 'Ovarian hormones through Wnt signalling regulate the growth of human and mouse ovarian cancer initiating lesions', Oncotarget, 7 64836-64853 (2016) [C1]
Bajwa P, Nagendra PB, Nielsen S, Sahoo SS, Bielanowicz A, Lombard JM, et al., 'Age related increase in mTOR activity contributes to the pathological changes in ovarian surface epithelium', Oncotarget, 7 19214-19227 (2016) [C1]
Ovarian cancer is a disease of older women. However, the molecular mechanisms of ovarian aging and their contribution to the pathogenesis of ovarian cancer are currently unclear. ... [more]
Ovarian cancer is a disease of older women. However, the molecular mechanisms of ovarian aging and their contribution to the pathogenesis of ovarian cancer are currently unclear. mTOR signalling is a major regulator of aging as suppression of this pathway extends lifespan in model organisms. Overactive mTOR signalling is present in up to 80% of ovarian cancer samples and is associated with poor prognosis. This study examined the role of mTOR signalling in age-associated changes in ovarian surface epithelium (OSE). Histological examination of ovaries from both aged mice and women revealed OSE cell hyperplasia, papillary growth and inclusion cysts. These pathological lesions expressed bonafide markers of ovarian cancer precursor lesions, Pax8 and Stathmin 1, and were presented with elevated mTOR signalling. To understand whether overactive mTOR signalling is responsible for the development of these pathological changes, we analysed ovaries of the Pten trangenic mice and found significant reduction in OSE lesions compared to controls. Furthermore, pharmacological suppression of mTOR signalling significantly decreased OSE hyperplasia in aged mice. Treatment with mTOR inhibitors reduced human ovarian cancer cell viability, proliferation and colony forming ability. Collectively, we have established the role of mTOR signalling in age-related OSE pathologies and initiation of ovarian cancer.
Kumar M, Syed SM, Taketo MM, Tanwar PS, 'Epithelial Wnt/ßcatenin signalling is essential for epididymal coiling', Developmental Biology, 412 234-249 (2016) [C1]
© 2016 Elsevier Inc. Organ shape and size are important determinants of their physiological functions. Epithelial tubes are anlagen of many complex organs. How these tubes acquire... [more]
© 2016 Elsevier Inc. Organ shape and size are important determinants of their physiological functions. Epithelial tubes are anlagen of many complex organs. How these tubes acquire their complex shape and size is a fundamental question in biology. In male mice, the Wolffian duct (WD; postnatally known as epididymis) undergoes an astonishing transformation, where a straight tube only a few millimetres long elongates to over 1000 times its original length and fits into a very small space, due to extensive coiling of epithelium, to perform the highly specialized function of sperm maturation. Defective coiling disrupts sperm maturation and leads to male infertility. Recent work has shown that epithelial cell proliferation is a major driver of WD coiling. Still, very little is known about the molecular signals involved in this process. Testicular androgens are known regulators of WD development. However, epithelial androgen receptor signalling is dispensable for WD coiling. In this study, we have shown that Wnt signalling is highly active in the entire WD epithelium during its coiling, and is limited to only a few segments of the epididymis in later life. Pharmacological and genetic suppression of Wnt signalling inhibited WD coiling by decreasing cell proliferation and promoting apoptosis. Comparative gene expression analysis identified Fibroblast growth factor 7 (Fgf7) as a prime Wnt target gene involved in WD coiling and in vitro treatment with Fgf7 protein increased coiling of WDs. In summary, our work has established that epithelial canonical Wnt signalling is a critical regulator of WD coiling and its precise regulation is essential for WD/epididymal differentiation.
Kumar M, Camlin NJ, Holt JE, Teixeira JM, McLaughlin EA, Tanwar PS, 'Germ cell specific overactivation of WNT/beta catenin signalling has no effect on folliculogenesis but causes fertility defects due to abnormal foetal development', SCIENTIFIC REPORTS, 6 (2016) [C1]
Tanwar PS, Mohapatra G, Chiang S, Engler DA, Zhang L, Kaneko-Tarui T, et al., 'Loss of LKB1 and PTEN tumor suppressor genes in the ovarian surface epithelium induces papillary serous ovarian cancer', CARCINOGENESIS, 35 546-553 (2014) [C1]
Tanwar PS, Kaneko-Tarui T, Lee HJ, Zhang LH, Teixeira JM, 'PTEN loss and HOXA10 expression are associated with ovarian endometrioid adenocarcinoma differentiation and progression', Carcinogenesis, 34 893-901 (2013) [C1]
Epithelial ovarian cancer is a heterogeneous disease that is subdivided into five major histotypes but the mechanisms driving their differentiation are not clear. Mutations in ade... [more]
Epithelial ovarian cancer is a heterogeneous disease that is subdivided into five major histotypes but the mechanisms driving their differentiation are not clear. Mutations in adenomatous polyposis coli (APC) and ß-catenin are commonly observed in the human ovarian endometrioid adenocarcinoma (OEA) patients. However, the mechanisms subsequent to APC deletion in ovarian tumorigenesis have not been well characterized. We have conditionally deleted APC in the murine ovarian surface epithelium (OSE) and showed that its loss leads to development of epithelial inclusion cysts. High-grade OEAs with tightly packed villoglandular histology were observed in older APC-deleted mice. Phosphatase and tensin homolog (PTEN) expression was elevated in the early lesions but lost after progression to the more advanced tumors. Knockdown of APC or expression of a gain-of-function ß-catenin similarly induced human OSE cells to develop tumors with endometrioid histology in xenografts. Expression of HOXA10 was induced in both the advanced APC-deleted murine tumors and in the tumor xenografts of human OSE cells with knocked-down APC. These results show that reduced APC activity is sufficient to induce formation of epithelial inclusion cysts and support OEA development and suggest that induced HOXA10 expression and loss of PTEN are key mechanisms driving endometrioid histotype differentiation and progression. © The Author 2012.Published by Oxford University Press. All rights reserved.
Tanwar PS, Kaneko-Tarui T, Zhang L, Teixeira JM, 'Altered LKB1/AMPK/TSC1/TSC2/mTOR signaling causes disruption of sertoli cell polarity and spermatogenesis', Human Molecular Genetics, 21 4394-4405 (2012) [C1]
Tanwar PS, Kaneko-Tarui T, Zhang L, Tanaka Y, Crum CP, Teixeira JM, 'Stromal liver kinase B1 STK11 signaling loss induces oviductal adenomas and endometrial cancer by activating mammalian target of Rapamycin Complex 1', PLOS Genetics, 8 1-14 (2012) [C1]
|Show 40 more journal articles|
Conference (50 outputs)
Brown Y, Jamaluddin MFB, Ghosh A, Mellick AS, Murtha L, Boyle A, Tanwar PS, 'The Glue of Cancer Cell Life: Characterization of the Acellular Component of High Grade Serous Ovarian Cancer Identifies Potential Novel Drug Targets', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2018)
Jamaluddin MFB, Ko Y-A, Ius Y, O'Sullivan R, Nahar P, Jaaback K, Tanwar PS, 'Why Targeted Therapies Don't Work?: Proteomic Characterization of Intratumor Heterogeneity of Human Endometrial Cancer', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2018)
|2017||Ghosh A, Tanwar PS, 'Looking through the tube: Secretory cells act as the oviductal epithelial stem/progenitor cells', Perth (2017)|
|2016||Jhamb M, Syed SM, Tanwar PS, 'Developing shapes: Epithelial Wnt signaling is required for epididymal coiling', Newcastle (2016)|
|2016||Bajwa P, Tanwar PS, 'mTOR signaling in the initiation and progression of ovarian cancer', Sydney (2016)|
Sahoo SS, Tanwar PS, 'Inhibition of extracellular matrix mediated TGFß signalling suppress endometrial cancer metastasis', Sydney (2016)
|2016||Nagendra PB, Goad J, Nielsen S, Rassam L, Lombard JM, Nahar P, Tanwar PS, 'Serous Ovarian Cancer: A synchrony of mutations and hormones', Sydney (2016)|
|2015||Kumar M, Goad J, Syed S, Tanwar PS, 'Twists and Turns: Balanced Wnt signalling is essential for epididymal coiling', Adelaide, SA, Australia (2015) [E3]|
|2015||Bajwa P, Tanwar PS, 'Age related increase in mTOR activity contributes to the pathogenesis of ovarian cancer', Lorne, Vic, Australia (2015) [E3]|
|2015||Tanwar PS, Sahoo S, 'Extracellular matrix mediated TGFß signalling supports endometrial cancer metastasis', Lorne, Vic, Australia (2015) [E3]|
|2015||Goad J, Kumar M, Syed S, Tanwar PS, 'Gone with the Wnt: Unopposed oestrogen leads to endometrial cancer by regulating Wnt signaling', Adelaide, SA, Australia (2015) [E3]|
|2015||Sercombe L, Sahoo S, Tanwar PS, 'mTORC1 hyperactivation induces the ovarian phenotype of PCOS', Adelaide, SA, Australia (2015) [E3]|
|2015||Goad J, Syed S, Tanwar PS, 'Synergistic effect of unopposed oestrogen and overactive Wnt signalling in endometrial cancer', Newcastle, NSW, Australia (2015) [E3]|
|2015||Syed S, Goad J, Sahoo S, Cardona J, Kumar J, Tanwar P, 'Endometrial hyperplasia and cancer: Side effects of miscommunication', Adelaide, SA, Australia (2015) [E3]|
|2015||Syed S, Goad J, Sahoo S, Cardona J, Tanwar PS, 'Influence of bad neighborhood: Stromal contribution to endometrial cancer development', Newcastle, NSW, Australia (2015) [E3]|
|2014||Kumar M, Sahoo SS, Tanwar P, 'MTOR: A NOVEL TARGET FOR TESTICULAR CANCER', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Newcastle, NSW (2014) [E3]|
|2014||Tanwar PS, Kaneko-Tarui T, Teixeira JM, 'Constitutive Wnt/B-Catenin Signaling in Mice in the Absence of Mullerian Inhibiting Substance/AntiMulleiran Hormone Signaling Leads to the Development of a Polycystic Ovary Phenotype', REPRODUCTIVE SCIENCES, Florence, ITALY (2014) [E3]|
|2013||Tanwar PS, 'Frequent alterations in mTOR signaling in human ovarian serous carcinomas', 25th Lorne Cancer Conference, Lorne, Victoria, Australia (2013) [E3]|
|2013||Tanwar PS, 'The Müllerian Inhibiting Substance type 2 receptor is an endogenous tumor suppressor and its loss phenocopies PTEN loss or activation of Kras in testes with sustained ßcatenin signaling', Society of Reproductive Biology Endocrine Society of Australia Annual Scientific Meeting, Sydney, NSW, Australia (2013) [E3]|
|2013||Tanwar PS, 'Preclinical models of ovarian cancer: PI3K-mTOR signalling axis', Translational Cancer Research Conference, Newcastle, NSW, Australia (2013) [E3]|
|Show 47 more conferences|
Grants and Funding
|Number of grants||1|
Click on a grant title below to expand the full details for that specific grant.
20191 grants / $483,404
Funding body: NHMRC (National Health & Medical Research Council)
|Funding body||NHMRC (National Health & Medical Research Council)|
|Project Team||Associate Professor Pradeep Tanwar|
|Scheme||Career Development Fellowships|
|Type Of Funding||Aust Competitive - Commonwealth|
Number of supervisions
|Commenced||Level of Study||Research Title||Program||Supervisor Type|
|2018||PhD||Rapamycin in Nanoparticles: A Possible Therapy for Ovarian Cancer||PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2017||PhD||Neurotrophic growth factors and their receptors as biomarkers and therapeutic targets in human cancers||PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle||Co-Supervisor|
|2017||PhD||A Neuronal Biomarker for Aggressive Prostate Cancer||PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle||Co-Supervisor|
|2017||PhD||Nerve Dependence in Human Cancers||PhD (Medicine), Faculty of Health and Medicine, The University of Newcastle||Co-Supervisor|
|2016||PhD||The Role of Tumour Microenvironment in Ovarian Cancer||PhD (Pharmacy), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2015||PhD||The Role of mTOR Hyperactivation in the Pathogenesis of PCOS||PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2015||PhD||Early serous ovarian carcinogenesis : Understanding the genetic and lifestyle factors||PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2015||Masters||Investigating the Role of Microenvironment and Matrix Stiffness in Ovarian Cancer Development||M Philosophy (Medical Biochem), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2015||PhD||Levels of Steroids and Endometrial Proteins as an Infertility Indicators Markers in Women with Reproductive Pathologies of Immune Origin.||PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2014||PhD||To Study the Female Lower Reproductive Tract Cell Dynamics, Homeostasis and Cancer||PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|Year||Level of Study||Research Title||Program||Supervisor Type|
|2019||PhD||Genesis of Ovarian Cancer: Understanding the Mechanisms of Oviductal Epithelial Cell Homoeostasis||PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2018||PhD||Role of WNT Signalling in Endometrial Homeostasis and Cancer||PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2018||PhD||Endometrial Stem/Progenitor Cells in Endometrial Regeneration, Carcinogenesis and Aging||PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2018||PhD||Age-related mTOR in Ovarian and Endometrial Cancers||PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2018||PhD||Role of Microenvironment in Endometrial Cancer Progression, Metastasis, and Drug Resistance||PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2018||Honours||The role of epithelial Wnt/β-Catenin signalling in uterine development||Biochemistry & Cell Biology, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle||Principal Supervisor|
|2017||PhD||Wnt Signalling in Germ Cells and Reproductive Tract Development||PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2017||Honours||OVARIAN SOMATIC STEM/PROGENITOR CELLS AND THEIR ROLE IN OVARIAN FUNCTIONS AND DISEASES||Biological Sciences, Faculty of Health and Medicine, University of Newcastle||Principal Supervisor|
|2015||Honours||The Role of mTOR Hyperactivation in the Pathogenesis of PCOS||Biochemistry & Cell Biology, The University of Newcastle||Principal Supervisor|
|2015||Honours||Interrogating nuclear organisation and the transcription factory model using cytotrophoblast to syncytiotrophoblast differentiation||Biological Sciences, Faculty of Engineering and Built Environment - The University of Newcastle (Australia)||Co-Supervisor|
The map is a representation of a researchers co-authorship with collaborators across the globe. The map displays the number of publications against a country, where there is at least one co-author based in that country. Data is sourced from the University of Newcastle research publication management system (NURO) and may not fully represent the authors complete body of work.
|Country||Count of Publications|
August 13, 2018
August 9, 2017
September 6, 2016
September 1, 2016
March 12, 2015
November 8, 2013
Associate Professor Pradeep Tanwar
NHMRC Career Development Fellow
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine
|Phone||(02) 4921 5148|
|Building||Life Sciences Building: 236|
Callaghan, NSW 2308