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GET /v1/research/project/?format=api&offset=240&ordering=-end_planned
{ "count": 2260, "next": "https://api-test.medunigraz.at/v1/research/project/?format=api&limit=20&offset=260&ordering=-end_planned", "previous": "https://api-test.medunigraz.at/v1/research/project/?format=api&limit=20&offset=220&ordering=-end_planned", "results": [ { "id": 8537, "title": { "de": "AlveOlism: Wie Fettstoffwechsel Lungenregeneration fördert", "en": "AlveOlism: How Lipid CatabOlism fuels AlveOlar Regeneration" }, "short": "AlveOlism", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2024-04-01T02:00:00+02:00", "begin_effective": "2025-01-01T01:00:00+01:00", "end_planned": "2028-03-31T02:00:00+02:00", "end_effective": "2028-12-31T01:00:00+01:00", "assignment": "2024-12-03T09:54:10+01:00", "program": 72, "subprogram": null, "organization": 14006, "category": 10, "type": 10, "partner_function": 4, "manager": 57409, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "PAT9976323", "ethics_committee": null, "edudract_number": null, "persons": [ "8537-57409-10", "8537-112150-12" ] }, { "id": 8356, "title": { "de": "CXCR4 role in the anabolic response of teriparatide in bone ", "en": "CXCR4 role in the anabolic response of teriparatide in bone " }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2024-10-01T02:00:00+02:00", "begin_effective": "2024-10-01T02:00:00+02:00", "end_planned": "2028-03-31T02:00:00+02:00", "end_effective": "2028-03-31T02:00:00+02:00", "assignment": "2024-08-19T14:37:04+02:00", "program": 72, "subprogram": null, "organization": 14028, "category": 10, "type": 10, "partner_function": 4, "manager": 107134, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "PAT4629323", "ethics_committee": null, "edudract_number": null, "persons": [ "8356-50464-12", "8356-56571-12", "8356-107134-10", "8356-110967-12", "8356-129458-12", "8356-122433-12", "8356-124131-12" ] }, { "id": 8506, "title": { "de": "Medizinische Entscheidungen bei der Multisystematrophie: Entwicklung einer\r\npersonalisierten, bestmöglichen medizinischen Versorgung mit integrierter Telemedizin und\r\nmobiler Palliativversorgung für Personen mit Multisystematrophie- Eine monozentrische,\r\nrandomisierte, offene klinische Studie mit verblindeter Bewertung der motorischen Progression\r\nwährend des Interventionszeitraums", "en": "Medical Decision Making in Multiple System Atrophy: developing personalized best medical care with integrated telemedicine and mobile palliative care for individuals with multiple system atrophy - A monocentric, randomized, open-label clinical study with rater\u0002blinded evaluation of motor progression over the interventional period" }, "short": "MeDeMSA Care", "url": null, "abstract": { "de": "Das Lebensende stellt MSA-Patienten, ihre Betreuer und behandelnden Ärzte vor zahlreiche ethische Dilemmata: Vorenthaltung oder Entzug von Medikamenten, Nahrungsverweigerung vs. Gastrostomie, invasive Beatmung, Anordnung der Nicht-Wiederbelebung. \r\nAdvanced Care Planning (ACP) ist ein wichtiger fortlaufender Kommunikationsprozess, bei dem Patienten das klinische Team über ihre Werte, Ziele und Präferenzen bei der medizinischen Behandlung während schwerer und chronischer Krankheiten informieren können. ACP ist ein Instrument zur Förderung der Autonomie von Patienten und ihres individuellen Konzepts von Lebensqualität (QoL), aber die ethische Perspektive wurde in der besonderen Situation von Menschen, die mit MSA leben, noch nicht systematisch in den Blick genommen.\r\nDie wichtigsten Forschungsfragen in diesem Projekt sind: Welche Wünsche und Vorstellungen haben Menschen mit MSA von einem würdigen Lebensende? Wie ist es möglich, die Lebensqualität dieser Menschen und ihrer Betreuer zu verbessern?\r\nUm diese Fragen zu beantworten, werden Menschen mit MSA und ihre Betreuer, die für die Interventionsstudie MeDeMSA PA3 rekrutiert wurden, zu halbstrukturierten Interviews zu Beginn der Studie und 12 Monate nach den Interventionsmaßnahmen eingeladen (Kallio, Pietilä, Johnson, & Kangasniemi, 2016). \r\nZiel ist es, die Präferenzen der Patienten und des Pflegepersonals in Bezug auf die Beteiligung an Entscheidungen in der Gesundheitsversorgung zu bewerten, welche Art der Informationsvermittlung für ihren Entscheidungsprozess relevant ist, wie sie Telemedizin und mobile Palliativversorgung wahrnehmen, deren rechtliche und regulatorische Aspekte und schließlich ihre Sicht auf die Arzt-Patienten-Beziehung und ihr Konzept der Lebensqualität, das für die ACP wesentlich ist.\r\nUm diese Ziele zu erreichen, sind folgende Arbeitsschritte geplant: i. Eine systematische Übersicht über den ethischen und Stand der Technik in Bezug auf die gemeinsame Entscheidungsfindung, ethische Richtlinien, ACP, Gesetze und Vorschriften in Bezug auf Lebensende und Palliativversorgung bei neurodegenerativen Erkrankungen; ii. eine Umfrage zum Autonomie-Präferenz-Index bei Menschen mit MSA, die in PA3 rekrutiert wurden, und deren Betreuer; iii. ein dynamischer Beitrag zu den klinischen MeDeMSA Sitzungen des klinischen MeDeMSA-Ausschusses; iv. eine eingehende Beschäftigung mit der Telemedizin für Menschen mit MSA und die Bewertung ihrer und ethischen Aspekte und die Entwicklung eines bioethischen Rahmens und von Aufklärungsmaterial für MSA-Patienten und ihre Betreuer. In ständiger enger Zusammenarbeit mit den anderen PA der MeDeMSA RG ist es das Ziel einen bioethischen Rahmen für patientenzentrierte medizinische Entscheidungen im MeDeMSA-Versorgungskreis zu schaffen.", "en": "End of life challenges MSA patients, their caregivers and treating physicians with many ethical dilemmas: withholding or withdrawing medications, food refusal vs. gastrostomy feeding, invasive ventilation, the do\u0002not-resuscitate order. \r\nAdvanced care planning (ACP) is an important ongoing process of communication, where patients can inform the clinical team about their values, goals and preferences in medical treatment during serious and chronic illness. ACP is an instrument to promote autonomy of patients and their individual concept of quality of life (QoL), but the ethical perspective has not been systematically focused on in the peculiar setting of people living with MSA yet.\r\nThe main research questions in this PA are: what are the wishes and perceptions of a decent end-of-life for people living with MSA? How is it possible to improve the QoL of these people and their caregivers?To answer these questions, people with MSA and their care-givers recruited in the interventional trial of MeDeMSA PA3 will be invited to join semi-structured interviews at the study begin and 12 months into the interventional procedures (Kallio, Pietilä, Johnson, & Kangasniemi, 2016). \r\nThe aim is to evaluate the patients’ and caregivers’ preferences for involvement in health-care decisions, which kind of information communication is \r\nrelevant for their decision-making process, which is their perception of telemedicine and mobile palliative care, the legal and regulatory aspects thereof and, ultimately, their perspectives on the patient–physician relationship and their concept of QoL, which is essential for ACP.\r\nTo achieve these goals the following worksteps are planned: i. A systematic review of the ethical and regulatory state of the art on shared-decision making, ethical guidelines, ACP, laws and regulations related to end-of life and palliation in neurodegenerative disorders; ii. an Autonomy Preference Index survey of people with MSA recruited in PA3 and their care-givers; iii. a dynamic contribution to the clinical MeDeMSA board meetings; iv. an in-depth focus on telemedicine for people with MSA and the assessment of its regulatory and ethical aspects and v. the development of a bioethical framework and educational material for MSA patients and their caregivers. In permanent close cooperation with the other PA of the MeDeMSA RG, the aim of PA5 is to establish a bioethical framework for patient-centered medical decisions in the MeDeMSA circle of care." }, "begin_planned": "2024-10-01T02:00:00+02:00", "begin_effective": "2024-10-01T02:00:00+02:00", "end_planned": "2028-03-31T02:00:00+02:00", "end_effective": "2028-03-31T02:00:00+02:00", "assignment": "2024-11-19T16:44:54+01:00", "program": 113, "subprogram": null, "organization": 14051, "category": 10, "type": 10, "partner_function": 4, "manager": 50172, "contact": null, "status": 2, "research": 2, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "FG 2705 - B ", "ethics_committee": null, "edudract_number": null, "persons": [ "8506-50172-10" ] }, { "id": 8784, "title": { "de": "Diagnostische Herausforderungen bei der klinischen Alzheimer-Erkennung: Einsatz von blutbasiertem Phospho-Tau 217 zur Verbesserung der diagnostischen Genauigkeit in österreichischen Gedächtnisambulanzen", "en": "Addressing Challenges in Clinical Alzheimer’s Diagnosis: Blood-Based Phospho-Tau 217 to Improve Diagnostic Accuracy in Austrian Memory Clinics" }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2025-05-01T02:00:00+02:00", "begin_effective": "2025-05-01T02:00:00+02:00", "end_planned": "2028-03-31T02:00:00+02:00", "end_effective": "2028-03-31T02:00:00+02:00", "assignment": "2025-04-15T18:49:25+02:00", "program": null, "subprogram": null, "organization": 14051, "category": 10, "type": 10, "partner_function": 4, "manager": 73547, "contact": null, "status": 2, "research": 2, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 2269 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "8784-73547-10" ] }, { "id": 8066, "title": { "de": "Digitalisierung von innovativen Pflegeprozessen\r\nzur Entlastung und Befähigung von Pflegenden\r\n", "en": "Digitalisation of Innovative Care Processes\r\nto Unburden and Empower Nurses" }, "short": "N!CA", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2024-03-01T01:00:00+01:00", "begin_effective": "2024-03-01T01:00:00+01:00", "end_planned": "2028-02-29T01:00:00+01:00", "end_effective": "2028-02-29T01:00:00+01:00", "assignment": "2024-03-04T14:49:46+01:00", "program": 94, "subprogram": null, "organization": 14509, "category": 10, "type": 10, "partner_function": 2, "manager": 63683, "contact": null, "status": 2, "research": 2, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 416 ], "funder_projectcode": "FO999904895", "ethics_committee": null, "edudract_number": null, "persons": [ "8066-63683-10" ] }, { "id": 8012, "title": { "de": "Metabo-typisierung von Nahrungentzug zur Krebstherapie", "en": "Metabotyping Nutrient Deprivation Response in Cancer Therapy" }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2024-03-01T01:00:00+01:00", "begin_effective": "2024-03-01T01:00:00+01:00", "end_planned": "2028-02-28T01:00:00+01:00", "end_effective": "2028-02-28T01:00:00+01:00", "assignment": "2024-02-05T08:38:21+01:00", "program": 72, "subprogram": null, "organization": 14017, "category": 10, "type": 10, "partner_function": 4, "manager": 99151, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "PAT1744223", "ethics_committee": null, "edudract_number": null, "persons": [ "8012-85979-12", "8012-99151-10", "8012-107135-12", "8012-126115-12" ] }, { "id": 9148, "title": { "de": "Biosynthetisiertes Porphyrin-beladenes Hydrogel für die photodynamische Therapie von multiresistenter Candida albicans bei HIV-infizierten Patienten", "en": "Biosynthesised porphyrin loaded hydrogel for photodynamic\r\ntherapy of multidurg-resistant Candida albicans in HIV infected\r\npatients" }, "short": "BioPor-PDT", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2026-03-01T01:00:00+01:00", "begin_effective": "2025-12-01T01:00:00+01:00", "end_planned": "2028-02-28T01:00:00+01:00", "end_effective": "2027-11-30T01:00:00+01:00", "assignment": "2025-08-14T16:24:27+02:00", "program": 254, "subprogram": null, "organization": 14012, "category": 10, "type": 10, "partner_function": 1, "manager": 124253, "contact": null, "status": 2, "research": 2, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 20 ], "funder_projectcode": "P161", "ethics_committee": null, "edudract_number": null, "persons": [ "9148-124253-10" ] }, { "id": 9556, "title": { "de": "Österreichisch-afrikanische Forschungskooperation zur Untersuchung des toxikologischen und immunpharmakologischen Potenzials von kenianischem Khat (Catha edulis) zur Verbesserung nachhaltiger Lebensgrundlagen in Kenia\r\n", "en": "Austria-Africa Research Collaboration on Exploring the Toxicological and Immunopharmacological Potential of Kenyan Khat (Catha edulis) for Enhancing Quality Livelihoods in Kenya" }, "short": "Österr-afrikan Koop_kenianisches Khat", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2026-03-01T01:00:00+01:00", "begin_effective": "2026-03-01T01:00:00+01:00", "end_planned": "2028-02-28T01:00:00+01:00", "end_effective": "2028-02-29T01:00:00+01:00", "assignment": "2026-01-26T11:52:19+01:00", "program": 254, "subprogram": null, "organization": 14022, "category": 10, "type": 10, "partner_function": 1, "manager": 60706, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 20 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "9556-60706-10" ] }, { "id": 9226, "title": { "de": "Data Stewards für interoperables Management klinischer Daten innerhalb der Mission Cancer an der Med Uni Graz", "en": "Data stewards for interoperable clinical data management within the Cancer Mission at the Medical University of Graz" }, "short": "DS Mission Cancer", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2026-02-02T01:00:00+01:00", "begin_effective": "2026-02-02T01:00:00+01:00", "end_planned": "2028-02-01T01:00:00+01:00", "end_effective": "2028-02-01T01:00:00+01:00", "assignment": "2025-09-26T11:17:21+02:00", "program": 255, "subprogram": null, "organization": 28083, "category": 10, "type": 10, "partner_function": 4, "manager": 57544, "contact": null, "status": 2, "research": 10, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 416 ], "funder_projectcode": "FO999929811", "ethics_committee": null, "edudract_number": null, "persons": [ "9226-57544-10" ] }, { "id": 7304, "title": { "de": "Steirische Kinderkrebsforschung - Forschungseinheit für Krebserkrankungen und Störungen des Blutes und Immunsystems bei Kindern \r\n", "en": "Styrian Children's Cancer Research - Research Unit for Childhood Cancer and Inborn Errors of the Blood or Immunity" }, "short": "Steirische Kinderkrebsforschung", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2023-02-01T01:00:00+01:00", "begin_effective": "2023-01-01T01:00:00+01:00", "end_planned": "2028-01-31T01:00:00+01:00", "end_effective": "2027-12-31T01:00:00+01:00", "assignment": "2022-12-15T14:14:16+01:00", "program": null, "subprogram": null, "organization": 14092, "category": 10, "type": 10, "partner_function": 4, "manager": 85188, "contact": null, "status": 2, "research": 2, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 1550 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "7304-85188-10" ] }, { "id": 8578, "title": { "de": "OptimaMind - Verbesserung der kognitiven Funktion durch Ernährung", "en": "OptimaMind - Enhancing cognitive longevity through lifestyle and nutrition" }, "short": "OptimaMind", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2025-02-03T01:00:00+01:00", "begin_effective": "2025-02-03T01:00:00+01:00", "end_planned": "2028-01-31T01:00:00+01:00", "end_effective": "2028-01-31T01:00:00+01:00", "assignment": "2025-01-03T17:54:51+01:00", "program": 112, "subprogram": null, "organization": 28392, "category": 10, "type": 10, "partner_function": 2, "manager": 89175, "contact": null, "status": 2, "research": 2, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "PIN8074224", "ethics_committee": null, "edudract_number": null, "persons": [ "8578-89175-10" ] }, { "id": 8609, "title": { "de": "Exogene eletrische und mechanische Stimulation durch eletronische Haut stimuliert die Zellprofileration der oralen Mundschleimhaut", "en": "Exogenous electrical and mechanical motion stimulation by using an electronic skin for support oral cell proliferation." }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2025-02-01T01:00:00+01:00", "begin_effective": "2025-06-01T02:00:00+02:00", "end_planned": "2028-01-31T01:00:00+01:00", "end_effective": "2028-05-31T02:00:00+02:00", "assignment": "2025-01-21T17:58:12+01:00", "program": null, "subprogram": null, "organization": 14017, "category": 10, "type": 10, "partner_function": 4, "manager": 133140, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "ESP6372324", "ethics_committee": null, "edudract_number": null, "persons": [ "8609-133140-10" ] }, { "id": 8589, "title": { "de": "Rejuvenated yeasts for better biorefineries", "en": "Rejuvenated yeasts for better biorefineries" }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2025-01-31T01:00:00+01:00", "begin_effective": "2025-01-31T01:00:00+01:00", "end_planned": "2028-01-30T01:00:00+01:00", "end_effective": "2028-01-30T01:00:00+01:00", "assignment": "2025-01-10T10:29:19+01:00", "program": 94, "subprogram": null, "organization": 14012, "category": 10, "type": 10, "partner_function": 1, "manager": 113130, "contact": null, "status": 2, "research": 2, "grant": 10, "event": null, "study": null, "language": null, "funders": [], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "8589-113130-10", "8589-132237-12" ] }, { "id": 8142, "title": { "de": "TARgetinG disease pErsisTence and progression of\r\nMyeloProliferative Neoplasms", "en": "TARgetinG disease pErsisTence and progression of\r\nMyeloProliferative Neoplasms" }, "short": "TARGET MPN", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2024-01-01T01:00:00+01:00", "begin_effective": "2024-06-01T02:00:00+02:00", "end_planned": "2028-01-01T01:00:00+01:00", "end_effective": "2028-07-10T02:00:00+02:00", "assignment": "2024-04-18T12:35:12+02:00", "program": null, "subprogram": null, "organization": 14085, "category": 10, "type": 10, "partner_function": 4, "manager": 107132, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "I06944", "ethics_committee": null, "edudract_number": null, "persons": [ "8142-107132-10", "8142-134381-12", "8142-101484-12", "8142-126596-12" ] }, { "id": 8189, "title": { "de": "Orphan Device für pädiatrische Patienten: eine einzigartige Plattform mit innovativen Dienstleistungen", "en": "Orphan Device for paediatric patients: a unique platform providing innovative services" }, "short": "OrphaDev4kids", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2025-01-01T01:00:00+01:00", "begin_effective": "2024-07-01T02:00:00+02:00", "end_planned": "2028-01-01T01:00:00+01:00", "end_effective": "2027-06-30T02:00:00+02:00", "assignment": "2024-05-08T10:42:03+02:00", "program": null, "subprogram": "EU4H-2023-PJ", "organization": 14052, "category": 10, "type": 10, "partner_function": 2, "manager": 50785, "contact": null, "status": 2, "research": 2, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 10 ], "funder_projectcode": "101161377", "ethics_committee": null, "edudract_number": null, "persons": [ "8189-50785-10" ] }, { "id": 8362, "title": { "de": "MEK Inhibition bei RAS-mutierter/EZH2-inaktivierter CMML", "en": "MEK inhibition in RAS-mutated/EZH2-inactivated CMML" }, "short": null, "url": null, "abstract": { "de": "Forschungskontext/theoretischer Rahmen:\r\nDie chronische myelomonozytäre Leukämie (CMML) ist eine aggressive hämatopoetische Neoplasie, die häufig auf Aberrationen zurückzuführen ist, die die RAS-Onkogene verändern (RASmut). Leider sind die derzeitigen therapeutischen Ansätze für RASmut-CMML-Patienten unzureichend. Wir zeigen, dass RASmut bei CMML häufig mit inaktivierenden Aberrationen des epigenetischen Modifikators EZH2 (EZH2inact) einhergeht. In-vitro-Zellkulturstudien zeigen, dass myeloische Zellen mit RASmut/EZH2inact eine Hyperaktivierung der RAS-Signaltransduktion aufweisen und besonders stark auf eine RAS-MAPK/ERK-Inhibition mit MEK-Inhibitoren (MEKi) reagieren.\r\n\r\nHypothesen/Forschungsfragen/Zielsetzungen:\r\nForschungsfrage: \r\nWir fragen, ob unterschiedliche pharmakologische Ansätze therapeutisch auf RASmut/EZH2inact CMML abzielen können.\r\nHypothese: \r\nWir stellen die Hypothese auf, dass RASmut und EZH2inact synergistisch RAS-Signalwege in CMML aktivieren und eine erhöhte Empfindlichkeit gegenüber MEKi verleihen.\r\nZielsetzungen: \r\nDurch die strategische Einbindung unserer Biobank mit klinisch gut annotierten Patientenproben in modernste In-vitro- und In-vivo-Ansätze werden wir zunächst unser Wissen über die Auswirkungen des gemeinsamen Auftretens von RASmut/EZH2inact auf die RAS-MAPK/ERK-Signalübertragung bei CMML erweitern. Anschließend werden wir die MEKi-Therapie in diesen Modellen analysieren und nach einer bevorzugten Empfindlichkeit des RASmut/EZH2inact-Genotyps fragen. Schließlich werden wir die Auswirkungen von MEKi auf RASmut/EZH2inact CMML-Leukämie-Stammzellen (LSC) und die klonale Evolution untersuchen. \r\n\r\nHerangehensweise/Methoden:\r\nWir werden zunächst die Auswirkungen von EZH2inact auf die Aktivierung der RASmut-Signalübertragung in transgenen In-vivo-Mausmodellen, primären CMML-Patientenproben und von Patienten stammenden Xenografts (PDX) untersuchen. Diese Analysen werden die durchflusszytometrische Bewertung des RAS-signalisings in hämatopoetischen Stamm- und Vorläuferzellen (HSPC) und LSC umfassen. Anschließend werden wir diese Modelle verwenden, um die Auswirkungen des gleichzeitigen Auftretens von RASmut/EZH2inact auf MEKi zu bewerten. Letztendlich wollen wir das therapeutische Potenzial von MEKi zur Heilung von RASmut/EZH2inact CMML bewerten. Daher werden wir die Auswirkungen der MEKi-Behandlung auf RASmut/EZH2inact-HSPC-Kompartimente, CMML-LSC und die klonale Evolution der CMML untersuchen. \r\n\r\nGrad der Originalität/Innovation:\r\nDie gezielte Beeinflussung der aberranten RAS-Signalübertragung ist seit Jahrzehnten ein wichtiger Forschungsschwerpunkt. Obwohl seit kurzem direkte RAS-Inhibitoren der nächsten Generation zur Verfügung stehen, war der therapeutische Nutzen für RASmut-CMML-Patienten begrenzt. Dieses Projekt untersucht einen neuartigen Ansatz und schlägt vor, dass eine erfolgreiche molekular gesteuerte Behandlung bei RASmut CMML den Einfluss von koexistierenden und funktionell interagierenden Läsionen berücksichtigen muss.\r\n\r\nBeteiligte Hauptforscher:\r\nArmin Zebisch, der über eine langjährige Erfahrung auf dem Gebiet der RAS-Signalübertragung bei myeloischen Neoplasien verfügt, wird der Hauptforscher sein. Er wird von klinischen Hämatologen und Grundlagenforschern unterstützt, die über profunde Kenntnisse der CMML und der in diesem Projekt verwendeten Modelle verfügen. Ein Doktorand und ein Techniker werden sein Laborteam bei der Durchführung dieses Projekts unterstützen.\r\n", "en": "Wider research context/theoretical framework:\r\nChronic myelomonocytic leukemia (CMML) is an aggressive hematopoietic neoplasia and is frequently driven by aberrations modifying the RAS oncogenes (RASmut). Unfortunately, current therapeutic approaches for RASmut CMML patients are insufficient. We demonstrate that RASmut in CMML often co-occur with inactivating aberrations of the epigenetic modifier EZH2 (EZH2inact). In-vitro cell culture studies reveal that RASmut/EZH2inact myeloid cells exhibit RAS-signaling hyperactivation and might be preferentially sensitive to RAS-MAPK/ERK inhibition with MEK inhibitors (MEKi).\r\n\r\nHypotheses/research questions/objectives:\r\nResearch question: \r\nWe ask whether distinctive pharmacological approaches can therapeutically target RASmut/EZH2inact CMML.\r\nHypothesis:\r\nWe hypothesize that RASmut and EZH2inact synergistically activate RAS-signaling pathways in CMML and confer increased sensitivity to MEKi.\r\nObjectives: \r\nBy strategically incorporating our biobank with clinically well-annotated patient specimens into state-of-the-art in-vitro and in-vivo approaches, we will initially extend our knowledge on the effects of RASmut/EZH2inact co-occurrence on RAS-MAPK/ERK signaling in CMML. We will then analyze MEKi therapy within these models and ask for preferential sensitivity in the RASmut/EZH2inact genotype. Ultimately, we will assess the effects of MEKi on RASmut/EZH2inact CMML-leukemic stem cells (LSC) and clonal evolution. \r\n\r\nApproach/methods:\r\nWe will initially elaborate on the effects of EZH2inact on the activation of RASmut-signaling in transgenic murine in-vivo models, primary CMML patient specimens, and patient-derived xenografts (PDX). These analyses will include the flow-cytometry-based assessment of RAS-signaling in hematopoietic stem and progenitor cells (HSPC) and LSC. We will then use these models to assess the effects of RASmut/EZH2inact co-occurrence on MEKi. Ultimately, we will aim to assess the therapeutic potential of MEKi to cure RASmut/EZH2inact CMML. Therefore, we will study the effects of MEKi treatment on RASmut/EZH2inact HSPC compartments, CMML-LSC and clonal evolution of CMML. \r\nLevel of originality/innovation\r\nTargeting aberrant RAS signaling has been a significant focus of research for the last decades. Despite the recent advent of direct next-generation RAS inhibitors, the therapeutic benefit for RASmut CMML patients was limited. This project assesses a novel approach and proposes that successful molecular-guided treatment in RASmut CMML must consider the influence of co-existing and functionally interacting lesions.\r\nPrimary researchers involved\r\nArmin Zebisch has a strong track record on RAS-signaling in myeloid neoplasms and will be the principal investigator. He will be supported by clinical hematologists and basic researchers with profound expertise in CMML and the models used within this project. A PhD student and technician will further support his lab team in executing this project.\r\n" }, "begin_planned": "2025-01-01T01:00:00+01:00", "begin_effective": "2025-01-01T01:00:00+01:00", "end_planned": "2028-01-01T01:00:00+01:00", "end_effective": "2029-12-31T01:00:00+01:00", "assignment": "2024-08-21T15:56:58+02:00", "program": 72, "subprogram": null, "organization": 14082, "category": 10, "type": 10, "partner_function": 4, "manager": 57402, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "PAT 1753824", "ethics_committee": null, "edudract_number": null, "persons": [ "8362-57402-10", "8362-97430-12", "8362-97983-12", "8362-50116-12" ] }, { "id": 8459, "title": { "de": "Succinat als Signalmolekül in der menschlichen Plazenta", "en": "Succinate as Signaling Molecule in the human Placenta" }, "short": "Succinat_Signalmolekül_menschlPlazenta", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2025-01-01T01:00:00+01:00", "begin_effective": "2024-12-01T01:00:00+01:00", "end_planned": "2027-12-31T01:00:00+01:00", "end_effective": "2028-11-30T01:00:00+01:00", "assignment": "2024-10-21T11:54:18+02:00", "program": 72, "subprogram": null, "organization": 14022, "category": 10, "type": 10, "partner_function": 4, "manager": 51756, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "PAT8808224", "ethics_committee": null, "edudract_number": null, "persons": [ "8459-51756-10", "8459-100879-11", "8459-106867-12", "8459-111587-12", "8459-132258-12" ] }, { "id": 7719, "title": { "de": "MSc in Entrepreneurship in Digital Health", "en": "MSc in Entrepreneurship in Digital Health" }, "short": "EDITH", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2023-02-01T01:00:00+01:00", "begin_effective": "2023-01-01T01:00:00+01:00", "end_planned": "2027-12-31T01:00:00+01:00", "end_effective": "2027-12-31T01:00:00+01:00", "assignment": "2023-08-11T14:38:26+02:00", "program": 211, "subprogram": null, "organization": 14076, "category": 10, "type": 10, "partner_function": 3, "manager": 54332, "contact": null, "status": 2, "research": 10, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 3059 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "7719-54332-10" ] }, { "id": 9299, "title": { "de": "Prädiktive Marker und Pathomechanismen der Krankheitsprogression bei Mycosis fungoides", "en": "Predictive markers and pathomechanisms of mycosis fungoides disease progression: Integrating Spatial Transcriptomics and In Situ Analysis of archived FFPE samples" }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2025-10-01T02:00:00+02:00", "begin_effective": "2025-10-01T02:00:00+02:00", "end_planned": "2027-12-31T01:00:00+01:00", "end_effective": "2027-09-30T02:00:00+02:00", "assignment": "2025-11-06T09:08:00+01:00", "program": null, "subprogram": null, "organization": 14047, "category": 10, "type": 10, "partner_function": 4, "manager": 118468, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 1161 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "9299-118468-10" ] }, { "id": 8761, "title": { "de": "Innovative Ansätze für die Implantationsforschung in Gesundheit und Krankheit", "en": "Innovative approaches to implantation research in health and disease" }, "short": "IMPLANTEU", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2025-01-01T01:00:00+01:00", "begin_effective": "2024-10-01T02:00:00+02:00", "end_planned": "2027-12-31T01:00:00+01:00", "end_effective": "2028-09-30T02:00:00+02:00", "assignment": "2025-04-09T16:15:10+02:00", "program": 209, "subprogram": null, "organization": 14017, "category": 10, "type": 10, "partner_function": 1, "manager": 53232, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 10 ], "funder_projectcode": "101169308", "ethics_committee": null, "edudract_number": null, "persons": [ "8761-53232-10" ] } ] }