成人大片

• Biography/ Background

  My research group focuses broadly on intercellular communication, cell-matrix interactions and resulting morphogenesis in normal function and cancer of the reproductive organs.

   

  Coordinated structural remodelling of the ovarian follicle to promote maturation and ovulation of oocytes

  Our primary focus is on the cyclic remodelling of the ovary during folliculogenesis, atresia, ovulation and luteinisation.  Together these processes determine reproductive success and the health the oocyte and hence a healthy start to life. 

  Australia has one of the highest rates of dependence on Assisted Reproductive Technology (ART) internationally, resulting in over 4,000 births (~3%) annually.  Gamete insufficiency is the main cause of infertility and determinant of embryo health and subsequent ART success.   Our aims are; 1. To reveal the molecular mechanism of controlled tissue morphogenesis in ovaries, and understand how the changing ovarian environment promotes oocyte quality.  2. To develop diagnostic and therapeutic means to enhance the health of women and their babies in natural fertility and ART as well as to develop the technology for in vitro maturation of oocytes.

  Health risks from ovarian dysfunction.  Infertility and polycystic ovary syndrome are both extremely common in the Australian population and both associate with dysregulated ovarian tissue remodelling.  Infertility treatment carries serious risks for women due to invasive hormone stimulations, surgical procedures and multiple pregnancies.  All the above may be prevented through our work, by understanding the mechanisms of ovarian function and dysfunction and perfecting therapies to address these directly.  

  Specific Research Projects are Addressing

  ·         Identifying bioarkers of oocyte developmental competence

  ·         Molecular mechanisms of ovulation

  ·         Development and function of the ovarian lymphatic system

  ·         Molecular control of primordial ovarian follicle activation

   

  Development and progression of cancers of reproductive organs

  Extracellular matrix remodelling and tissue morphogenesis also cause metastases of reproductive organ cancers which are among the most prevalent cancers in men and women.  Cancer of the breast, prostate, ovary and female reproductive tract account for more than 40% of all cancers in the Australian population (Cancer in Australia: an overview 2006. AIHW Publications 2006;37:144).  One in eight Australian women will develop breast cancer and one in 9 men will develop prostate cancer.  Each year 3000 women die from breast cancer, and a similar number of men die from prostate cancer, Cancer that progresses to metastatic stage in breast, ovary, prostate or reproductive tracts are usually incurable and thus my work also focuses on understanding how cancers become metastatic and how this can be prevented to improve ageing productively.

  Our research seeks to understand the biological basis underlying the cause and mechanism of progression to metastatic disease.  The changes that arise in malignant tissue to endow their capacity to degrade local extracellular matrix barriers and invade local blood and/or lymphatic vessels for transport to distal sites is under investigation. From this foundation we aim to develop tests to identify patients at risk of metastatic disease as well as antimetastatic therapies that specifically target and block the capacity of tumor cells to invade local tissues, to migrate and to populate new tissues, the main processes through which metastatic spread occurs.

  Specific research projects are addressing:

  ·         The interaction of tumor cells with local non-malignant stromal tissues

  ·         Proteases of the Adamts family that facilitate degradation of peritumoral ECM

  ·         Tumor mediated angiogenesis and lymphangiogenesis

   

  Research Funding

  NHMRC Project Grants

  ARC Discovery Grant

  Prostate Cancer Foundation Grant

   

  Russell Lab Team

  Dr Darryl Russell PhD ARC Future Fellow

  Laura Watson BSc (Hons) Research Assistant

  Kathryn Gebhardt BSc (Hons) Post Doc

  Izza Tan BSc (Hons) PhD student

  Adrian Kaczmarek BSc (Hons) PhD Student

• Publications

  Selected Recent Publications

   

  Robker RL, Akison LK, Bennett BD, Thrupp P, Chura LN,  Russell DL, Lane M, Norman RN.
  Obese Women Exhibit Differences in Ovarian Metabolites, Hormones, and Gene Expression Compared with Moderate-Weight Women
  J Clin Endocrinol Metab 2009, 94(5) 1533-1540

  Ricciardelli C, Sakko AJ, Ween MP, Russell DL, Horsfall DJ
  The biological role and regulation of versican levels in cancer.
  Cancer Metastasis Rev. 2009,  28(1-2):233-45

  Dunning KR, Cashman K, Russell DL, Thompson JG, Normal RN, Robker RL
  Beta-Oxidation Is Essential for Mouse Oocyte Developmental Competence and Early Embryo Development .
  Biol Reprod: 2010; 83(6):909-918

  Wu LLY, Dunning KR, Yang X, Russell DL Lane M Norman RN Robker RL
  High-Fat Diet Causes Lipotoxicity Responses in Cumulus-Oocyte Complexes and Decreased Fertilization Rates
  Endocrinology  2010, 151(11):5438-5445

  Brown HM, Robker RL, Russell DL
  Development and Hormonal Regulation of the Ovarian Lymphatic Vasculature
  Endocrinology  2010, 151(11): 5446-5455

  Yang X, Dunning KR, Wu LLY, Hickey TE, Norman RN, Russell DL, Liang XY, Robker RL
  Identification of Perilipin-2 as a lipid droplet protein regulated in oocytes during maturation
  Reprod Fertil Dev 2010, 22(8):1262-1271

  Brown HM, Dunning KR, Robker RL, Russell DL
  ADAMTS1 Cleavage of Versican Mediates Essential Structural Remodeling of the Ovarian Follicle and Cumulus-Oocyte Matrix During Ovulation in Mice
  Biol Reprod  2010, 83(4):549-557

  Sasseville M, Ritter LJ, Nguyen TM, Liu F, MottersheadDG, Russell DL, Gilchrist RB
  Growth differentiation factor 9 signaling requires ERK1/2 activity in mouse granulosa and cumulus cells
  J Cell Sci  2010 , 123 (18): 3166-3176

  Tam KKY, Russell DL, Peet DJ, Bracken CP, Rodgers RJ, ThompsonJG, Kind KL.
  Hormonally regulated follicle differentiation and luteinization in the mouse is associated with hypoxia inducible factor activity
  Mol Cell Endocrinol 2010, 327(1-2): 47-55

  Gebhardt KM, Dunning KR, Feil D, Lane M, Russell DL. 
  Human cumulus cell gene expression as a biomarker of pregnancy outcome following single embryo transfer. 
  Fertil Steril. 2011. 96(1):47-52.

  Dunning KR, Akison LK, Russell DL, Norman RJ, Robker RL. 
  Increased beta-oxidation and improved oocyte developmental competence in response to l carnitine during ovarian in vitro follicle development in mice. 
  Biol Reprod. 2011. 85(3):548-55.

  Wu LL, Russell DL, Norman RJ, Robker RL. 
  Endoplasmic reticulum (ER) stress in cumulus-oocyte complexes impairs pentraxin-3 secretion, mitochondrial membrane potential and embryo development.
  Mol Endocrinol. 2012. 26(4):562-73.

  Akison LK, Alvino ER, Dunning KR, Robker RL, Russell DL. 
  Transient invasive migration in mouse cumulus oocyte complexes induced at ovulation by luteinizing hormone. 
  Biol Reprod. 2012. 86(4):125.

  Watson, LN, Mottershead, DG, Dunning, KR, Robker, RL, Gilchrist, RB, Russell, DL. 
  Heparan sulfate proteoglycans regulate responses to oocyte paracrine signals in ovarian follicle morphogenesis.
  Endocrinology. 2012. 153(9):4544-4555.

  Frank LA, Sutton-McDowall ML, Russell DL, Wang X, Feil DK, Gilchrist RB, Thompson JG.  
  Effect of varying glucose and glucosamine concentration in vitro on mouse oocyte maturation and developmental competence.
  Reprod Fertil Dev. 2012 Nov 7. PMID:23131421[PubMed - as supplied by publisher]

  Kind KL, Banwell KM, Gebhardt KM, Macpherson A, Gauld A, Russell DL, Thompson JG. 
  Microarray analysis of mRNA from cumulus cells following in vivo or in vitro maturation of mouse cumulus-oocyte complexes.
  Reprod Fertil Dev. 2013;25(2):426-38. doi: 10.1071/RD11305.

  Dunning KR, Watson LN, Sharkey DJ, Brown HM, Norman RJ, Thompson JG, Robker RL, Russell DL. 
  Molecular filtration properties of the mouse expanded cumulus matrix: controlled supply of metabolites and extracellular signals to cumulus cells and the oocyte.
  Biol Reprod. 2012 Oct 18;87(4):89

  de Arao Tan I, Ricciardelli C, Russell DL. 
  The metalloproteinase ADAMTS1: A comprehensive review of its role in tumorigenic and metastatic pathways.
  Int J Cancer. 2013 Nov 15;133(10):2263-76.

   

Entry last updated: Tuesday, 29 Mar 2022

To link to this page, please use the following URL:  /directory/darryl.russell