A5048961794- Sperm and Testicular Function
- Reproductive Biology and Fertility
- PARP inhibition in cancer therapy
- Renal and related cancers
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- DNA Repair Mechanisms
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Acute Myeloid Leukemia Research
- Retinoids in leukemia and cellular processes
- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
- MicroRNA in disease regulation
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- Melanoma and MAPK Pathways
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Genomics and Chromatin Dynamics
- NF-κB Signaling Pathways
- Cancer-related molecular mechanisms research
- Sarcoma Diagnosis and Treatment
- Cancer Cells and Metastasis
- Prostate Cancer Treatment and Research
Hudson Institute of Medical Research
2020-2024
Monash University
2015-2024
Australian Regenerative Medicine Institute
2013-2022
Hudson Institute
2020
Discovery Institute
2019
Beth Israel Deaconess Medical Center
2008-2015
Cancer Research Institute
2015
Cancer Genetics (United States)
2005-2012
Harvard University
2009-2012
Harvard University Press
2007-2012
A microRNA network regulates the tumor suppressor PTEN in prostate cancer.
A human renin/prorenin receptor (RER) has recently been cloned. To gain insight into the molecular function of RER, we studied its signal transduction mechanisms. Initially, found a ubiquitous and intracellular expression pattern RER. Consistently, observed several transcriptional start sites high promoter activity We could identify transcription factor promyelocytic zinc finger (PLZF) protein as direct interaction partner C-terminal domain RER by yeast 2-hybrid screening...
Some gammadelta and alphabeta T lymphocytes exhibit an "innate" phenotype associated with rapid cytokine responses. The PLZF transcription factor is essential for the innate of NKT cells. This report shows that likewise responsible innate, NKT-like Vgamma1+Vdelta6.3/Vdelta6.4+ TCR cross-linking induced expression in all polyclonal immature thymocytes, suggesting agonist selection might be required induction. Transgenic Vgamma1Vdelta6.4 was sufficient to support development large numbers...
Abstract Spermatogonial stem cells (SSCs) are at the foundation of mammalian spermatogenesis. Whereas rare Asingle spermatogonia comprise rodent SSC pool, primate spermatogenesis arises from more abundant Adark and Apale spermatogonia, identity cell is subject to debate. The fundamental differences between these models highlight need investigate biology SSCs, which have greater relevance human physiology. alkylating chemotherapeutic agent, busulfan, ablates in rodents causes infertility...
Hematopoietic stem cells in the bone marrow give rise to lymphoid progenitors, which subsequently differentiate into B and T lymphocytes. Here we show that proto-oncogene LRF plays an essential role versus cell-fate decision. We demonstrate is key for instructing early progenitors mice develop lineage by repressing cell-instructive signals produced signal protein, Notch. propose a new model commitment, acts as master regulator of cell's determination lineage.
Male mice lacking expression of Plzf, a DNA sequence-specific transcriptional repressor, show progressive germ cell depletion due to exhaustion the spermatogonial stem population. This is likely deregulated genes controlling switch between self-renewal and differentiation. Here we that Plzf directly represses transcription kit, hallmark both endogenous kit reporter gene under control promoter region. A discrete sequence promoter, required for Plzf-mediated repression, bound by in vivo vitro....
Abstract The broad-complex tramtrack and bric a brac-zinc finger transcriptional regulator(BTB-ZF), promyelocytic leukemia zinc (PLZF), was recently shown to control the development of characteristic innate T cell phenotype effector functions NK cells. Interestingly, ectopic expression PLZF push conventional cells into an activated state that seems be proinflammatory. factors normal in lymphocytes are unknown. In this study, we show is not restricted but also expressed by subset γδ cells,...
Abstract Mammalian spermatogenesis is sustained by mitotic germ cells with self-renewal potential known as undifferentiated spermatogonia. Maintenance of spermatogonia and dependent on tightly co-ordinated transcriptional post-transcriptional mechanisms. The RNA helicase DDX5 expressed but roles in are unexplored. Using an inducible knockout mouse model, we characterise essential role for spermatogonial maintenance show that Ddx5 indispensable male fertility. We demonstrate regulates...
The role of stem cells in tissue maintenance is appreciated and hierarchical models cell self-renewal differentiation often proposed. Stem activity the male germline restricted to undifferentiated A-type spermatogonia (Aundiff); however, only a fraction this population act as undisturbed testis Aundiff hierarchy remains contentious. Through newly developed compound reporter mice, here we define molecular signatures self-renewing differentiation-primed adult fractions dissect heterogeneity by...
In normal epidermis, β1 integrin expression is confined to the basal layer, whereas in hyperproliferative integrins are also expressed suprabasal layers. Transgenic mice which suprabasally via involucrin promoter have a sporadic psoriatic phenotype; however, mechanism by contribute pathogenesis of psoriasis unknown. We observed activation mitogen-activated protein kinase (MAPK) and keratinocytes human transgenic mouse lesions healing skin wounds, correlating each case with expression....
Prostate cancer is the most prevalent in males, and treatment options are limited for advanced forms of disease. Loss PTEN TP53 tumor suppressor genes commonly observed prostate cancer, whereas their compound loss often cancer. Here, we show that PARP inhibition triggers a p53-dependent cellular senescence PTEN-deficient setting prostate. Surprisingly, also find PARP-induced morphed into an apoptotic response upon p53. We further superactivation prosurvival PI3K-AKT signaling pathway limits...
Conditional inactivation of mTor has little effect in adult mouse prostate, but suppresses tumor initiation and progression.
Sustained spermatogenesis in adult males and fertility recovery following germ cell depletion are dependent on undifferentiated spermatogonia. We previously demonstrated a key role for the transcription factor SALL4 spermatogonial differentiation. However, whether has broader roles within spermatogonia remains unclear despite its ability to co-regulate genes with PLZF, required maintenance. Through development of inducible knockout models, we show that short-term integrity differentiating...