A5027343683- Multiple Myeloma Research and Treatments
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Sperm and Testicular Function
- Extracellular vesicles in disease
- Acute Myeloid Leukemia Research
- Ubiquitin and proteasome pathways
- Renal and related cancers
- Cancer therapeutics and mechanisms
- Reproductive Biology and Fertility
- HIV/AIDS drug development and treatment
- Reproductive Health and Technologies
- Assisted Reproductive Technology and Twin Pregnancy
- Cell Adhesion Molecules Research
- Chronic Lymphocytic Leukemia Research
- Testicular diseases and treatments
- Hepatocellular Carcinoma Treatment and Prognosis
- Renal Transplantation Outcomes and Treatments
- Epigenetics and DNA Methylation
- Cholinesterase and Neurodegenerative Diseases
- Quinazolinone synthesis and applications
Monash University
2016-2025
Alfred Health
2015-2025
Australian Centre for HIV and Hepatitis Virology Research
2014-2024
The Alfred Hospital
2014-2024
Monash Alfred Psychiatry Research centre
2012-2023
Australian Regenerative Medicine Institute
2014
Monash Institute of Medical Research
2008-2009
Hudson Institute
2008
Histone deacetylases (HDAC) control gene expression through their ability to acetylate proteins, thereby influencing a diverse range of cellular functions. Class I HDAC (HDAC1-3 and 8) HDAC6 are predominantly upregulated in malignancies altered some cancers has significant prognostic implication. The consequence dysregulated HDAC6, key players multiple myeloma (MM), unknown. This study hypothesized that MM patients with high have significantly poorer outcomes. Quantitative PCR for 11 (Class...
Abstract Therapeutic options are limited for elderly patients with acute myeloid leukemia (AML). A phase Ib/II study was undertaken to evaluate the maximum-tolerated dose (MTD) and preliminary efficacy of pan-histone deacetylase inhibitor panobinostat (LBH589) in combination azacitidine AML or high-risk myelodysplastic syndrome (MDS) naïve intensive chemotherapy. Thirty-nine (AML=29, MDS=10) received 75 mg/m 2 subcutaneously (days 1–5) oral (starting on day 5, thrice weekly seven doses)...
The transforming growth factor beta superfamily ligand activin A controls juvenile testis by stimulating Sertoli cell proliferation. Testicular levels are highest in the first postnatal week, when cells proliferating and spermatogonial stem form. Levels decrease sharply as proliferation ceases spermatogenic differentiation begins. We hypothesized that changing also affect germ maturation. detected an acute developmentally regulated impact of on Kit mRNA cocultures from Day 8, but not 4,...
The diagnosis of sperm DNA integrity is increasingly recognized as being crucial to inform the clinical course in infertile couples. An internationally accepted fragmentation assay that determines proportion and degree broken nuclear with recognised thresholds for identifying men at risk infertility Sperm Chromatin Structure Assay (SCSA®). In this study, SCSA® test was utilised evaluate relevance male age on quality total 6881 males Indian origin. Analysis proportions index (%DFI) high...
Mutational characterisation in extramedullary multiple myeloma (EM-MM) patients is challenging due to inaccessible EM plasmacytomas, unsafe nature of biopsies and the spatial temporal genomic heterogeneity apparent MM (Graphical abstract). Conventional monitoring disease burden through serum markers PET-CT, however these modalities are sometimes inadequate (serum markers), not performed a timely manner (PET-CT) uninformative for identifying mutations driving progression. DNA released into...
Germ cell testicular cancer is understood to arise during embryogenesis, based on the persistence of embryonic germ markers in carcinoma situ and seminoma. In this study, we examine potential seminoma-derived TCam-2 line be used as representative functional analyses We demonstrate expression several early markers, including BLIMP1, OCT3/4, AP2γ, NANOG KIT. Many TGF-beta superfamily receptors downstream transcription factors are also present these cells normally foetal ACTRIIA receptor,...
Abstract Histone deacetylase inhibitors (HDACi) are novel chemotherapeutics undergoing evaluation in clinical trials for the potential treatment of patients with multiple myeloma (MM). Although HDACi have demonstrable synergy when combined proteasome (PIs), recent evidence indicates that combination and PI is beneficial only a subset advanced MM, clearly indicating other rational combinations should be explored. In this context we hypothesized understanding molecular signature associated...
Antibody Secreting Cells (ASCs) are a fundamental component of humoral immunity, however, deregulated or excessive antibody production contributes to the pathology autoimmune diseases, while transformation ASCs results in malignancy Multiple Myeloma (MM). Despite substantial recent improvements treating these conditions, there is as yet no widely used ASC-specific therapeutic approach, highlighting critical need identify novel methods targeting normal and malignant ASCs. Surface molecules...
In this study, we evaluated the utility of extracellular RNA (exRNA) derived from plasma multiple myeloma (MM) patients for whole transcriptome characterization. exRNA 10 healthy controls (HC), five newly diagnosed (NDMM), and 12 relapsed refractory (RRMM) MM were analyzed compared. We showed that ~45% genes protein-coding ~85% identified covered >70%. Compared to HC, 632 differentially expressed (DEGs) in patients, which 26 common NDMM RRMM. further 54 191 specific RRMM, respectively, these...
Mutational characterisation utilising plasma (PL)-derived circulating tumour DNA (ctDNA) in multiple myeloma (MM) has been recently described. analyses of paired bone marrow (BM) MM cell and ctDNA from 76 patients (n = 24, new diagnosis (ND), n 52, relapsed/refractory (RR)) for (ras/raf signaling pathway) protein p53 (TP53) mutations using the OnTarget™ Mutation Detection (OMD) platform was performed. The total number proportions each compartments (BM-specific, PL-specific or shared)...
Circulating small extracellular vesicles (sEV) represent promising non-invasive biomarkers that may aid in the diagnosis and risk-stratification of multiple myeloma (MM), an incurable blood cancer. Here, we comprehensively isolated characterized sEV from human MM cell lines (HMCL) patient-derived plasma (psEV) by specific EV-marker enrichment morphology. Importantly, demonstrate HMCL-sEV are readily internalised stromal cells to functionally modulate proliferation. psEV were using various...
Over the last three decades changes in treatment paradigm for newly diagnosed multiple myeloma (MM) have led to a significant increase overall survival. Despite this, majority of patients relapse after one or more lines while acquiring resistance available therapies. Panobinostat, pan-histone deacetylase inhibitor, was approved by FDA 2015 with relapsed MM but how incorporate panobinostat most effectively into everyday practice remains unclear. Dysregulation Wnt canonical pathway, and its...
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In preclinical studies, oral azacitidine (CC-486), a hypomethylating agent, has been shown to have direct anti-MM effect and in vitro synergism when combined with lenalidomide (LEN). We present phase 1b, single center, 3 × dose escalation study planned expansion at maximum tolerated (MTD), which assessed the safety efficacy of combining CC-486 LEN (25 mg d1-21/28) dexamethasone (DEX) (40 weekly) patients relapsed/refractory MM who had previously failed LEN. Twenty-four were enrolled. The MTD...
To assess reduction in heavy menstrual bleeding and dysmenorrhea following MRI guided Focused Ultrasound Surgery (MRgFUS) of focal diffuse adenomyosis up to 12 months post-treatment a retrospective cohort study was done at tertiary care academic medical center for obstetrics, gynecology infertility.MRgFUS uterus thirty-seven patients presenting with symptoms MRI-suspected adenomyosis. The main outcome measure, bleeding, Symptom Severity Scoring (SSS) over 3, 6 month period. Secondary...
Summary Panobinostat is a pan‐deacetylase inhibitor that modulates the expression of oncogenic and immune‐mediating genes involved in tumour cell growth survival. We evaluated panobinostat‐induced post‐transplant responses identified correlative biomarkers patients with multiple myeloma who had failed to achieve complete response after autologous transplantation. Patients received panobinostat 45 mg administered three‐times weekly (TIW) on alternate weeks 28‐day cycles commencing 8–12...