Mr Manish Kumar Jhamb

Associate Lecturer

School of Biomedical Sciences and Pharmacy

Email:manishkumar.jhamb@newcastle.edu.au
Phone:(02) 4921 6934

Career Summary

Biography

Commitment, dedication, hard work and collaboration are the pillars of my research career in the area of reproductive sciences. My work mainly focuses on reproductive tract cancers. We aim to understand the normal reproductive tract development and abnormalities resulting in reproductive malignancies.

I submitted my PhD thesis very recently on February 08, 2017. I was fortunate to be supervised by two internationally known scientists in the field of oncology, Dr Pradeep Tanwar (principal supervisor) and Dr Hubert Hondermarck (co-supervisor). My PhD program of research is achieved by four first author and three co-author publications. I manage to publish all the papers before submission of my thesis and accorded with six national research recognitions. These publications and awards subsequently laid the foundations for me to start working as Associate Lecturer in the School of Biomedical Sciences & Pharmacy at the University of Newcastle which is priority research centre for research in reproductive sciences.

My research program focused on understanding the mechanisms involved in development, progression and metastasis of gynaecological malignancies. We are also keen to understand the genetic mutations that cause unlimited growth, survival and proliferation of cancer cells. I am very fortunate to have Dr Pradeep Tanwar, as my mentor who is a leader in the area of gynaecology oncology, and has a vast national and international (5-year post-doctoral Fellowship in gynaecology oncology at the Harvard Medical School, USA) experience in the field of cancer biology. Our lab has extensive national and international collaborations with the leading scientists in the field of reproductive system cancers which provides access to state of art facilities, latest technologies and relevant patient samples. This is advantageous for me to nurture and progress in the field of gynaecology oncology and attract peer-reviewed competitive funding for continuing my research in the field of gynaecology oncology. This will aid in expanding my research program to international level, establish collaborations and take it to translational grade.

Keywords

Developmental Biology
Gynaecology Oncology
Medical Biochemistry

Fields of Research

Code	Description	Percentage
060403	Developmental Genetics (incl. Sex Determination)	20
111201	Cancer Cell Biology	50
111203	Cancer Genetics	30

Professional Experience

UON Appointment

Title	Organisation / Department
Associate Lecturer	University of Newcastle School of Biomedical Sciences and Pharmacy Australia

Teaching

Code	Course	Role	Duration
HUBS2107	Mammalian Growth and Development The University of Newcastle This course will provide students with an overview of the biomolecular, cellular, genetic, physiological and anatomical aspects of reproductive growth and development, from the creation of the germ cells in the developing embryo to reproductive senescence in the ageing adult. The course will examine how sperm and eggs (gametes) are made; fertilisation achieved; and successful pregnancy initiated, maintained and stopped at birth. Developmental principles will be studied. The course will focus only on mammals with an emphasis on humans. Current research findings and techniques will be a key focus of this course.	Tutor	27/02/2017 - 24/05/2017

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Publications

For publications that are currently unpublished or in-press, details are shown in italics.

Journal article (12 outputs)

Year

Citation

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2018

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 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 m utation-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.

DOI	10.1210/en.2017-03018
Co-authors	Hubert Hondermarck, Mark Baker, Rodney Scott, Muhammad Jamaluddin, Pradeep Tanwar, Matt Dun

2017

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]

DOI	10.1210/en.2017-00519
Co-authors	Pradeep Tanwar

2017

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]

DOI	10.1016/j.ydbio.2017.01.015
Citations	Scopus - 5Web of Science - 4
Co-authors	Pradeep Tanwar

2017

Kumar M, Tanwar P, 'Organ Culture and Whole Mount Immunofluorescence Staining of Mouse Wolffian Ducts', JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, (2017) [C1]

DOI	10.3791/55134
Co-authors	Pradeep Tanwar

2016

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.

Co-authors	Murray Cairns, Pradeep Tanwar

2016

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 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 prolifera tion 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.

DOI	10.1016/j.ydbio.2016.02.025
Citations	Scopus - 7Web of Science - 7
Co-authors	Pradeep Tanwar

2014

Kumar M, Sahoo S, Tanwar PS, 'MTOR: A NOVEL TARGET FOR TESTICULAR CANCER', Asia-Pacific Journal of Clinical Oncology, 10 2-3 (2014)

Co-authors	Pradeep Tanwar

2013

Rani T, Yadav RC, Yadav NR, Kumar M, 'Effect of explant orientation on shoot regeneration in tomato (Lycopersicon esculentum)', INDIAN JOURNAL OF AGRICULTURAL SCIENCES, 83 514-517 (2013)

2013

Kumar M, Chand P, 'Comparison of Laboratory Prepared and Commercially Procured Antigen for the Diagnosis of Brucellosis in Buffaloes using Fluorescence Polarization Assay', Environment & Ecology, 31 29-32 (2013)

2013

Kumar M, Chand P, Chhabra R, Rani T, Kumar S, 'Brucellosis: An updated review of the disease', Indian Journal of Animal Sciences, 83 3-16 (2013)

2011

Kumar M, Chand P, 'Improvement in the diagnosis of Brucella abortus infections in naturally infected water buffaloes (Bubalus bubalis) using an ELISA with a Protein-G-based indicator system', Tropical Animal Health and Production, 43 1493-1499 (2011)

DOI	10.1007/s11250-011-9831-3

2011

Kumar M, 'Comparison of OPS-FITC Antigens Prepared from Crude OPS and Partially Purified OPS for Detecting B. abortus Antibodies in Buffaloes', Environment & Ecology, 31 47-49 (2011)

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