A5060810486- Acute Myeloid Leukemia Research
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Cancer Immunotherapy and Biomarkers
- Histone Deacetylase Inhibitors Research
- Advanced Biosensing Techniques and Applications
- Computational Drug Discovery Methods
- Cancer Cells and Metastasis
- 3D Printing in Biomedical Research
- Chronic Myeloid Leukemia Treatments
- Bioinformatics and Genomic Networks
- Single-cell and spatial transcriptomics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Microfluidic and Bio-sensing Technologies
- SARS-CoV-2 and COVID-19 Research
- Radiomics and Machine Learning in Medical Imaging
- Cancer therapeutics and mechanisms
- Cancer-related Molecular Pathways
- HIV/AIDS drug development and treatment
- Immune cells in cancer
- Cell Adhesion Molecules Research
- Microfluidic and Capillary Electrophoresis Applications
- AI in cancer detection
- Cell death mechanisms and regulation
Institute for Molecular Medicine Finland
2015-2024
University of Helsinki
2015-2024
Finland University
2013-2014
University of Turku
2013
University of Bergen
2013
Haukeland University Hospital
2013
Tampere University Hospital
2013
Tampere University
2013
Helsinki University Hospital
2013
Turku University Hospital
2013
We present an individualized systems medicine (ISM) approach to optimize cancer drug therapies one patient at a time. ISM is based on (i) molecular profiling and ex vivo sensitivity resistance testing (DSRT) of patients' cells 187 oncology drugs, (ii) clinical implementation predicted be effective, (iii) studying consecutive samples from the treated patients understand basis resistance. Here, application 28 with acute myeloid leukemia (AML) uncovered five major taxonomic drug-response...
Abstract We generated ex vivo drug-response and multiomics profiling data for a prospective series of 252 samples from 186 patients with acute myeloid leukemia (AML). A functional precision medicine tumor board (FPMTB) integrated clinical, molecular, application in clinical treatment decisions. Actionable drugs were found 97% AML, the recommendations clinically implemented 37 relapsed or refractory patients. report 59% objective response rate individually tailored therapies, including 13...
Viral diseases remain serious threats to public health because of the shortage effective means control. To combat surge viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced premature death cells infected with different RNA or DNA viruses, whereas, at same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited replication and spread....
Machine learning and single-cell data inform personalized drug combinations that selectively co-inhibit cancer cell populations.
The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using library of 75-78 clinically relevant drugs. included 132 viable tumor samples from 35 centers in seven countries. DSP was conducted on multicellular fresh tissue spheroid cultures 384-well plates with an overall mean processing time three weeks. In 89 cases...
Antibody phage display technology is well established and widely used for selecting specific antibodies against desired targets. Using conventional manual methods, it laborious to perform multiple selections with different antigens simultaneously. Furthermore, screening of the positive clones requires much effort. The authors describe optimized automated procedures these processes using a magnetic bead processor selection robotic station step. Both steps are performed in 96-well microplate...
The coronavirus disease 2019 (COVID-19) pandemic has heavily challenged the global healthcare system. Despite vaccination programs, new virus variants are circulating. Further research is required for understanding of biology severe acute respiratory syndrome 2 (SARS-CoV-2) infection and discovery therapeutic agents against virus. Here, we took advantage drug repurposing to identify if existing drugs could inhibit SARS-CoV-2 infection. We established an open high-throughput platform in vitro...
Central to the success of functional precision medicine solid tumors is perform drug testing patient-derived cancer cells (PDCs) in tumor-mimicking ex vivo conditions. While high throughput (HT) screening methods have been well-established for cultured two-dimensional (2D) format, this approach may limited value predicting clinical responses. Here, we describe results optimization sensitivity and resistance (DSRT) three-dimensional (3D) growth supporting matrices a HT mode (3D-DSRT) using...
Cancer therapy is increasingly becoming individualized, but there are also big gaps between the molecular knowledge of individual cancers we can generate today and what be applied in clinic. In an attempt to bridge this gap cancer genetic profiling clinically useful information, individualized systems medicine program has been established at Institute for Molecular Medicine Finland (FIMM), University Helsinki, Helsinki Hospital. Central drug sensitivity resistance testing (DSRT), which...
In vitro cancer drug testing carries a low predictive value. We developed the human leiomyoma–derived matrix “Myogel” to better mimic tumor microenvironment (TME). hypothesized that Myogel could provide an appropriate for cells, thereby allowing more in vivo–relevant testing. screened 19 anticancer compounds, targeting epidermal growth factor receptor (EGFR), MEK, and PI3K/mTOR on 12 head neck squamous cell carcinoma (HNSCC) lines cultured plastic, mouse sarcoma–derived Matrigel (MSDM),...
High throughput screening methods, measuring the sensitivity and resistance of tumor cells to drug treatments have been rapidly evolving. Not only do these screens allow correlating response profiles genomic features for developing novel predictors treatment response, but they can also add evidence therapy decision making in precision oncology. Recent analysis methods developed either assessing single agents or combination efficacies enable quantification dose-response curves with restricted...
Abstract Conventional chemotherapeutic agents are nonselective, often resulting in severe side effects and the development of resistance. Therefore, new molecular-targeted therapies urgently needed to be integrated into existing treatment regimens. Here, we performed a high-throughput compound screen identify synergistic interaction between ionizing radiation 396 anticancer compounds. The assay was run using five human papillomavirus (HPV)-negative head neck squamous cell carcinoma (HNSCC)...
We present a miniaturized immunofluorescence assay (mini-IFA) for measuring antibody response in patient blood samples. The method utilizes machine learning-guided image analysis and enables simultaneous measurement of immunoglobulin M (IgM), IgA, IgG responses against different viral antigens an automated high-throughput manner. relies on expressed through transfection, enabling use at low biosafety level fast adaptation to emerging pathogens. Using severe acute respiratory syndrome...
Establishment of drug testing patient-derived cancer cells (PDCs) in physiologically relevant 3-dimensional (3D) culture is central for discovery and research, as well functional precision medicine. Here, we describe the detailed protocol allowing 3D PDCs – or any type interest Matrigel 384-well plate format using automation. We also provide an alternative protocol, which does not require supporting matrices. The tissue obtained directly from clinics (after surgery biopsy) processed into...
The Rho family of Ras superfamily small GTPases regulates a broad range biological processes such as migration, differentiation, cell growth and survival. Therefore, the availability molecule modulators tool compounds could greatly enhance research on these proteins their function. To this end, we designed biochemical, high throughput screening assay with complementary follow-up assays to identify inhibiting MgcRacGAP, GTPase activating protein involved in cytokinesis transcriptionally...
The High Throughput Biomedicine (HTB) unit at the Institute for Molecular Medicine Finland FIMM was established in 2010 to serve as a national and international academic screening providing access state of art instrumentation chemical RNAi-based high throughput screening. initial focus multiwell plate based content microarray-based siRNA However, over first four years operation, has moved more flexible service platform where both is performed different scales primarily plate-based assays...
Abstract Gene products or pathways that are aberrantly activated in cancer but not normal tissue hold great promises for being effective and safe anticancer therapeutic targets. Many targeted drugs have entered clinical trials so far showed limited efficacy mostly due to variability treatment responses often rapidly emerging resistance. Towards more options, we will critically need multi-targeted drug combinations, which selectively inhibit the cells block distinct escape mechanisms become...
The epigenome plays a key role in cancer heterogeneity and drug resistance. Hence, number of epigenetic inhibitors have been developed tested cancers. major focus most studies so far has on the cytotoxic effect these compounds, only few investigated ability to revert resistant phenotype cells. there is need for systematic methodology unravel mechanisms behind sensitization. We high-throughput protocol screen non-simultaneous combinations, used it investigate reprogramming potential...
Head and neck squamous cell carcinoma (HNSCC) is a common cancer with five-year survival rate around 60%, indicating need for new treatments. BH3 mimetics are small molecules that inhibit anti-apoptotic Bcl-2 family proteins, resulting in apoptosis induction. We performed high-throughput screen using Myogel matrix to identify the synergy between irradiation novel A-1155463, A-1331852, navitoclax 12 HNSCC lines, normal (NOF) cancer-associated fibroblasts (CAF), dysplastic keratinocytes (ODA)....
Abstract Ovarian cancer (OvCa) is the sixth most common in women and a leading cause of death from gynecologic diseases. Poor prognosis OvCa due to late diagnosis acquired resistance conventional therapy. A significant setback for treatment lack reliable biomarkers effective targeted therapies. Our aim discover novel therapeutic opportunities with approved emerging drugs then translate actionable drug efficacies combinations as personalized therapy suggestions clinic. We have previously...