Srilakshmi Srinivasan
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- MicroRNA in disease regulation
- Prostate Cancer Treatment and Research
- Molecular Biology Techniques and Applications
- Blood Coagulation and Thrombosis Mechanisms
- RNA modifications and cancer
- Genetic Associations and Epidemiology
- Epigenetics and DNA Methylation
- Peptidase Inhibition and Analysis
- Cancer-related gene regulation
- Genomics and Rare Diseases
- Cell Adhesion Molecules Research
- RNA Interference and Gene Delivery
- Nanoparticle-Based Drug Delivery
- Genetic factors in colorectal cancer
- RNA regulation and disease
- Retinal and Optic Conditions
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Pancreatic function and diabetes
- Retinal Diseases and Treatments
- Vasculitis and related conditions
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Queensland University of Technology
2016-2025
Translational Research Institute
2014-2025
Narayana Nethralaya
2023
Eye Hospital in Bangalore
2017
Abstract Prostate cancer is the second most common malignancy among men worldwide. Genome-wide association studies have identified 100 risk variants for prostate cancer, which can explain approximately 33% of familial disease. We hypothesized that a comprehensive analysis genetic variations found within 3′ untranslated region genes predicted to affect miRNA binding (miRSNP) identify additional variants. investigated between 2,169 miRSNPs and in large-scale 22,301 cases 22,320 controls...
Abstract The timing of puberty is highly variable and associated with long-term health outcomes. To date, understanding the genetic control based largely on studies in women. Here, we report a multi-trait genome-wide association study for male an effective sample size 205,354 men. We find moderately strong genomic correlation between sexes (rg = 0.68) identify 76 independent signals timing. Implicated mechanisms include unexpected link natural hair colour, possibly reflecting common effects...
Abstract Background Prostate cancer is a broad-spectrum disease, spanning from indolent to highly aggressive lethal malignancy. cell lines are essential tools understanding the basic features of this malignancy, as well in identifying novel therapeutic strategies. However, most routinely used prostate research derived metastatic disease and may not fully elucidate molecular events underlying early stages development progression. Thus, there need for new localised better span spectrum....
Abstract Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the region from 71,535 cancer cases and 52,935 controls of European ancestry to define overall contribution germline variation at risk. We identify 12 independent risk signals ( p < 4.28 × 10 −15 ), three variants that have yet be reported. From polygenic score (PRS) model, derived assess cumulative effect 8q24, men in top 1% PRS 4-fold (95%CI =...
Genetic association studies have reported single-nucleotide polymorphisms (SNPs) at chromosome 19q13.3 to be associated with prostate cancer (PCa) risk. Recently, the rs61752561 SNP (Asp84Asn substitution) in exon 3 of kallikrein-related peptidase (KLK3) gene encoding prostate-specific antigen (PSA) was strongly PCa risk (P = 2.3 × 10-8). However, biological contribution has not been elucidated.Recombinant PSA protein variants were generated assess SNP-mediated biochemical changes by...
The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours numerous studies and is suggested a potential biomarker for cancer. KLK4 may also play role cancer progression through its involvement epithelial-mesenchymal transition, more aggressive phenotype, metastases bone. It well known that genetic variation the affect gene expression and/or various protein characteristics hence we sought investigate possible of single nucleotide...
Fusion transcripts are found in many tissues and have the potential to create novel functional products. Here, we investigate genomic sequences around fusion junctions better understand transcriptional mechanisms mediating transcription/splicing. We analyzed data from prostate (cancer) cells as previous studies shown extensively that these readily undergo transcription.We used FusionMap program identify high-confidence RNAseq data. The datasets were our (N = 8) other 14) clinical tumors with...
Kallikrein‐related peptidase 14 (KLK14) is one of the several secreted KLK serine proteases involved in prostate cancer (PCa) pathogenesis. While relatively understudied, recent reports have identified KLK14 as overexpressed during PCa development. However, modulation expression progression and molecular biological functions this protease tumor microenvironment remain unknown. To determine progression, we analyzed levels patient samples using publicly available databases...
Abstract Background KLK15 over-expression is reported to be a significant predictor of reduced progression-free survival and overall in ovarian cancer. Our aim was analyse the gene for putative functional single nucleotide polymorphisms (SNPs) assess association these HapMap tag SNPs with cancer survival. Results In silico analysis performed identify regulatory elements classify potentially regions. After SNP validation identification by DNA sequencing cell lines aggressive patients, 9 were...
MicroRNAs mediate biological processes through preferential binding to the 3' untranslated region (3' UTR) of target genes. Studies have shown their association with prostate cancer (PCa) risk single-nucleotide polymorphisms (SNPs), known as miRSNPs. In a European cohort, 22 PCa risk-associated miRSNPs been identified. The most significant miRSNP in UTR Kallikrein-related peptidase 3 (KLK3) created site for miR-3162-5p. Here we investigated miR-3162-5p-KLK interaction and clinical...
Abstract Risk classification for prostate cancer (PCa) aggressiveness and underlying mechanisms remain inadequate. Interactions between single nucleotide polymorphisms (SNPs) may provide a solution to fill these gaps. To identify SNP–SNP interactions in the four pathways (the angiogenesis-, mitochondria-, miRNA-, androgen metabolism-related pathways) associated with PCa aggressiveness, we tested 8587 SNPs 20,729 cases from consortium. We identified 3 KLK3 SNPs, 1083 ( P < 3.5 × 10 –9 )...
Abstract Kallikrein 14 (KLK14) has been proposed as a useful prognostic marker in prostate cancer, with expression reported to be associated tumour characteristics such higher stage and Gleason score. KLK14 also shown the potential predict cancer patients at risk of disease recurrence after radical prostatectomy. The KLKs are remarkably hormone-responsive family genes, although detailed studies androgen regulation have not undertaken date. Using vitro studies, we demonstrated that unlike...
Short tandem repeats (STRs) are repetitive sequences of a polymorphic stretch two to six nucleotides. We hypothesized that STRs associated with prostate cancer development and/or progression. undertook RNA sequencing analysis tumors and adjacent non-malignant cells identify readily expressed in these cells. Most the clinical samples mapped intronic intergenic DNA. Our indicated three (TAAA-ACTG2, TTTTG-TRIB1, TG-PCA3) differentially compared TG-PCA3 STR expression was repressed by...
With an estimated 1.1 million men worldwide diagnosed with prostate cancer yearly, effective and more specific biomarkers for early diagnosis could lead to better treatments. As such, novel genetic markers are sought this purpose. The tribbles homologue 1 gene (TRIB1) has recently shown have a role in tumorigenesis oncomine data-mining confirmed clinical significance of TRIB1 cancer. For the first time, polymorphic microsatellite been studied its potential association risk aggressiveness....
Next-generation sequencing techniques have revolutionized over the last decade providing researchers with low cost, high-throughput alternatives compared to traditional Sanger methods.These rapidly evolved from first-generation fourth-generation very broad applications such as unraveling complexity of genome, in terms genetic variations, and having a high impact on biological field.In this review, we discuss transition second-generation third-and fourthgenerations, describe some their novel...
Abstract Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.536 T > C; Ile163Thr-substitution PSA) associated reduced risk, however, functional relevance unknown. Here, we identify that SNP variant-induced change PSA biochemical activity mediates pathogenesis. ‘Thr’ variant leads to small subcutaneous tumours, supporting risk. However, also displays higher metastatic...