Dr Darryl Russell

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

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 [IF 2.8, Citations ]

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  May 14. [Epub ahead of print]

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
Bioogy of Reproduction 2011 In Press

Entry last updated: Wednesday, 19 Sep 2012