A5032474030- RNA and protein synthesis mechanisms
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Multiple Myeloma Research and Treatments
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Pancreatic and Hepatic Oncology Research
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Drug Transport and Resistance Mechanisms
- Cancer Mechanisms and Therapy
- RNA modifications and cancer
- Renal cell carcinoma treatment
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Bacterial Genetics and Biotechnology
- Dendrimers and Hyperbranched Polymers
- DNA and Nucleic Acid Chemistry
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Bacillus and Francisella bacterial research
- Advanced biosensing and bioanalysis techniques
- Soybean genetics and cultivation
- Cell Adhesion Molecules Research
- Chromosomal and Genetic Variations
- Genetics and Plant Breeding
- Bacteriophages and microbial interactions
Institute for Molecular Medicine Finland
2019-2024
University of Helsinki
2019-2024
University College Cork
2015-2019
National Institute of Plant Genome Research
2013-2014
Next-generation sequencing technologies provide opportunities to understand the genetic basis of phenotypic differences, such as abiotic stress response, even in closely related cultivars via identification large number DNA polymorphisms. We performed whole-genome resequencing three rice with contrasting responses drought and salinity (sensitive IR64, drought-tolerant Nagina 22 salinity-tolerant Pokkali). More than 356 million 90-bp paired-end reads were generated, which provided about 85%...
Nutrient-sensitive phosphorylation of the S6 protein 40S subunit eukaryote ribosome is highly conserved. However, despite four decades research, functional consequences this modification remain unknown. Revisiting enigma in Saccharomyces cerevisiae, we found that regulation Rps6 on Ser-232 and Ser-233 mediated by both TOR complex 1 (TORC1) TORC2. TORC1 regulates sites via poorly characterized AGC-family kinase Ypk3 PP1 phosphatase Glc7, whereas TORC2 only N-terminal phosphosite Ypk1. Cells...
DNA methylation plays a crucial role in development through inheritable gene silencing. Plants possess three types of methyltransferases (MTases), namely Methyltransferase (MET), Chromomethylase (CMT) and Domains Rearranged (DRM), which maintain at CG, CHG CHH sites. MTases have not been studied legumes so far. Here, we report the identification analysis putative five legumes, including chickpea, soybean, pigeonpea, Medicago Lotus. could be classified known MET, CMT, DRM nucleotide (DNMT2)...
Multiple myeloma (MM) is characterized by extensive immunoglobulin production leading to an excessive load on protein homeostasis in tumor cells. Aminopeptidases contribute proteolysis catalyzing the hydrolysis of amino acids from proteins or peptides and function downstream ubiquitin–proteasome pathway. Notably, aminopeptidases can be utilized delivery antibody peptide-conjugated drugs, such as melflufen, currently clinical trials. We analyzed expression 39 aminopeptidase genes MM samples...
Abstract Background Esterase enzymes differ in substrate specificity and biological function may display dysregulated expression cancer. This study evaluated the significance of esterase multiple myeloma (MM). Methods For gene profiling evaluation genomic variants Institute for Molecular Medicine Finland (FIMM) cohort, bone marrow aspirates were obtained from patients with newly diagnosed MM (NDMM) or relapsed/refractory (RRMM). CD138+ plasma cells enriched used RNA sequencing analysis, to...
The process of translation is characterized by irregularities in the local decoding rates specific mRNA codons. This includes occurrences long pauses that can take place when ribosomes decode certain peptide sequences, encounter strong RNA secondary structures, or “hungry” Examples are known where such pausing stalling used for regulating protein synthesis. be achieved at level via direct alteration ribosome progression through altering stability NoGo decay. Ribosome has also been implicated...
Despite several new therapeutic options, multiple myeloma (MM) patients experience relapses and inevitably become refractory to treatment. Insights into drug resistance mechanisms may lead the development of novel treatment strategies. The S100 family is comprised 21 calcium binding protein members with 17 genes located in 1q21 region, which commonly amplified MM. Dysregulated expression associated tumor initiation, progression inflammation. However, relationship between MM pathogenesis...
Synthesis of HIV GagPol involves a proportion ribosomes translating U6A shift site at the distal end gag gene performing programmed -1 ribosomal frameshift event to enter overlapping pol gene. In vitro studies here show that same motif reverse transcriptase generates and +1 indels with their ratio being sensitive relative concentration dNTPs specified by RNA template slippage-prone sequence its 5' adjacent base. The GGG 3' shift/slippage site, which is important for frameshifting, shown...
RNA dependent DNA-polymerases, reverse transcriptases, are key enzymes for retroviruses and retroelements. Their fidelity, including indel generation, is significant their use as reagents deep sequencing. Here, we report that certain template structures G-rich sequences, ahead of diverse transcriptases can be strong stimulators slippage at slippage-prone motif sequence 3' such 'slippage-stimulatory' structures. Where stimulated, the resulting products have one or more additional base(s)...
The role of TatD DNases as DNA repair enzymes or cell death (apoptotic) nucleases is well established in prokaryotes eukaryotes. current study aims to characterize the nuclease from Bacillus anthracis (Ba TatD) and explore its key histidine catalytic residues. Ba was found be a metal-dependent, nonspecific endonuclease which could efficiently cleave double-stranded substrates. Moreover, observed thermostable up 55°C act wide pH range indicating industrial applicability. Diethyl...
Immunoglobulin light-chain (AL) amyloidosis is a rare disease caused by clonal plasma cell secretion of misfolded light chains that assemble as toxic amyloid fibrils, depositing in vital organs including the heart and kidneys, causing organ dysfunction. Plasma cell-directed therapeutics are expected to reduce production chain eliminating amyloidogenic cells bone marrow, thereby diminishing fibril deposition providing potential for recovery. Melphalan flufenamide (melflufen) first-in-class...
Autism is a genetically complex neurobehavioral disorder with population prevalence of more than 1%. Cerebellar abnormalities, including Purkinje cell deficits in the vermis, are consistently reported and rodent models cerebellar dysfunction exhibit features analogous to human autism. We previously analysed regulation expression pseudoautosomal region 2 gene SPRY3, which adjacent X chromosome-linked TMLHE, known autism susceptibility gene. SPRY3 regulator branching morphogenesis strongly...
Abstract Many pediatric cancer patients with high-risk primary, refractory, or relapsed tumors still lack effective treatment strategies and frequently suffer from both acute delayed adverse drug effects, including secondary cancers. These are generally characterized by very few druggable molecular alterations, diminishing the advantage of genetics in defining patient-specific treatments. The purpose this study is to utilize functional precision medicine approach provide improved diagnostics...
Clear-cell renal cell carcinoma (ccRCC) is the most common origin of pancreatic metastases (PM). Distinct genomic aberrations, favorable prognosis, and clinical observations on high angiogenesis, succeeding tyrosine kinase inhibitor (TKI) sensitivity have been reported in PM-ccRCC. However, no functional or single-cell studies conducted thus far. We recruited five PM-ccRCC patients investigated genomic, transcriptomic, drug profiles their patient-derived cells (PDCs). The PM depicted both...
<title>Abstract</title> Pancreatic metastases (PM) of clear cell renal carcinoma (ccRCC) are rare, and little is known about them at patient level. The aim this study was to define the patient-specific characteristics PM-ccRCC matching patient-derived (PDC) cultures. We describe genomic single-cell transcriptomic profiles five patients with as well functional drug sensitivities their PDCs. First, patients’ tumors depicted both common novel somatic mutations copy number alterations, which...
Abstract Introduction: The esterase enzyme family is a subclass of the hydrolase superfamily that functions to split ester bonds. Several esterases have been identified, which differ in substrate specificity and biological function, expression specific may be dysregulated cancer. Limited information available regarding multiple myeloma (MM), despite potential for exploitation novel therapeutic approaches such as peptide-drug conjugates (e.g. melflufen). We evaluated significance MM. Methods:...
Background: Immunoglobulin light-chain amyloidosis (AL) is a rare disease caused by plasma cell secretion of misfolded light chains that assemble as amyloid fibrils, which deposit on vital organs causing organ dysfunction. Similar to AL, multiple myeloma (MM) also atypical (PC) expansion in the bone marrow. Although, much research has been done MM understand mechanisms and develop effective treatments, knowledge related AL still limited. Notably, there little information available regarding...