Project List
List projects.
Fields
id (integer)
Primary key.
Expansions
To activate relation expansion add the desired fields as a comma separated
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The following relational fields can be expanded:
organizationcategorytypepartner_functionmanagercontactstatusgrantresearcheventstudylanguageprogramfunders
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To filter for exact value matches:
?<fieldname>=<value>
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For advanced filtering use lookups:
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Possible advanced lookups:
begin_planned:gt,gte,lt,ltebegin_effective:gt,gte,lt,lteend_planned:gt,gte,lt,lteend_effective:gt,gte,lt,lte
GET /v1/research/project/?format=api&offset=2060&ordering=begin_effective
{ "count": 2264, "next": "https://api-test.medunigraz.at/v1/research/project/?format=api&limit=20&offset=2080&ordering=begin_effective", "previous": "https://api-test.medunigraz.at/v1/research/project/?format=api&limit=20&offset=2040&ordering=begin_effective", "results": [ { "id": 8455, "title": { "de": "Multi-Omics-Analyse von pulmonalen vaskulären Phänotypen bei COPD", "en": "Multi-omics analysis of pulmonary vascular phenotypes in COPD" }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2024-05-01T02:00:00+02:00", "begin_effective": "2024-10-01T02:00:00+02:00", "end_planned": "2025-04-30T02:00:00+02:00", "end_effective": "2025-09-30T02:00:00+02:00", "assignment": "2024-10-18T10:37:03+02:00", "program": 101, "subprogram": null, "organization": 14087, "category": 10, "type": 10, "partner_function": 2, "manager": 87980, "contact": null, "status": 2, "research": 2, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 15 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "8455-87980-10" ] }, { "id": 8218, "title": { "de": "TWINNING FOR EXCELLENCE TO ADVANCE RESEARCH IN THE ACTIVATION OF\r\nANTI-TUMOR IMMUNE RESPONSE AFTER ELECTROCHEMOTHERAPY COMBINED WITH GENE\r\nELETROTRANSFER OF pDNA ENCODING ICIs", "en": "TWINNING FOR EXCELLENCE TO ADVANCE RESEARCH IN THE ACTIVATION OF\r\nANTI-TUMOR IMMUNE RESPONSE AFTER ELECTROCHEMOTHERAPY COMBINED WITH GENE\r\nELETROTRANSFER OF pDNA ENCODING ICIs" }, "short": "ZAP Cancer", "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": "2027-04-30T02:00:00+02:00", "end_effective": "2027-09-30T02:00:00+02:00", "assignment": "2024-05-17T13:23:37+02:00", "program": null, "subprogram": null, "organization": 14085, "category": 10, "type": 10, "partner_function": 4, "manager": 107132, "contact": null, "status": 2, "research": 2, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 10 ], "funder_projectcode": "101160061", "ethics_committee": null, "edudract_number": null, "persons": [ "8218-99946-12", "8218-109501-12", "8218-107132-10", "8218-109002-11" ] }, { "id": 8127, "title": { "de": "LYVE-1 Hofbauer-Zellen bei Präeklampsie", "en": "LYVE-1 Hofbauer cells in preeclampsia" }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2024-03-01T01:00:00+01:00", "begin_effective": "2024-10-01T02:00:00+02:00", "end_planned": "2027-02-28T01:00:00+01:00", "end_effective": "2027-09-30T02:00:00+02:00", "assignment": "2024-04-05T10:35:43+02:00", "program": 111, "subprogram": null, "organization": 14017, "category": 10, "type": 10, "partner_function": 4, "manager": 53232, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "I06907", "ethics_committee": null, "edudract_number": null, "persons": [ "8127-53232-10", "8127-90214-12", "8127-93683-12", "8127-98902-12", "8127-106163-12", "8127-100900-12", "8127-119494-12", "8127-126134-12", "8127-128574-12" ] }, { "id": 8426, "title": { "de": "Immunometabolic biomarkers and therapeutic targets in multiple sclerosis", "en": "Immunometabolic biomarkers and therapeutic targets in multiple sclerosis" }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2024-09-01T02:00:00+02:00", "begin_effective": "2024-10-01T02:00:00+02:00", "end_planned": "2026-08-31T02:00:00+02:00", "end_effective": "2026-09-30T02:00:00+02:00", "assignment": "2024-10-07T16:32:04+02:00", "program": null, "subprogram": null, "organization": 14014, "category": 10, "type": 10, "partner_function": 1, "manager": 107391, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 1743 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "8426-107391-10" ] }, { "id": 8368, "title": { "de": "pan-European Management of Biological toxin incidents through standaRdisAtion initiatives for Crisis response Enhancement", "en": "pan-European Management of Biological toxin incidents through standaRdisAtion initiatives for Crisis response Enhancement" }, "short": "EMBRACE", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2024-08-01T02:00:00+02:00", "begin_effective": "2024-10-01T02:00:00+02:00", "end_planned": "2027-07-31T02:00:00+02:00", "end_effective": "2027-09-30T02:00:00+02:00", "assignment": "2024-08-22T12:03:14+02:00", "program": 213, "subprogram": null, "organization": 14020, "category": 10, "type": 10, "partner_function": 2, "manager": 51663, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 10 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "8368-50593-12", "8368-50861-12", "8368-95322-12", "8368-99430-12", "8368-51663-10", "8368-102187-12", "8368-101039-12", "8368-122831-12", "8368-126754-12" ] }, { "id": 8602, "title": { "de": "CoE MetAge – Zusatzfinanzierung", "en": "CoE MetAge – Zusatzfinanzierung" }, "short": "CoE MetAge – Zusatzfinanzierung", "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": "2029-09-30T02:00:00+02:00", "end_effective": "2029-09-30T02:00:00+02:00", "assignment": "2025-01-17T11:19:47+01:00", "program": null, "subprogram": null, "organization": 14012, "category": 10, "type": 10, "partner_function": 2, "manager": 91207, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 135 ], "funder_projectcode": "ABT12-338847/2024-12", "ethics_committee": null, "edudract_number": null, "persons": [ "8602-91207-10", "8602-98222-12", "8602-111387-12", "8602-111770-12" ] }, { "id": 8557, "title": { "de": "Services for Privacy Advancement through Generative AI and Model Sanitization", "en": "Services for Privacy Advancement through Generative AI and Model Sanitization" }, "short": "PRIVAGAMS", "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": "2026-09-30T02:00:00+02:00", "end_effective": "2026-09-30T02:00:00+02:00", "assignment": "2024-12-12T12:07:24+01:00", "program": null, "subprogram": null, "organization": 14020, "category": 10, "type": 10, "partner_function": 3, "manager": 51449, "contact": null, "status": 2, "research": 2, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 10 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "8557-51449-10", "8557-135503-12" ] }, { "id": 8294, "title": { "de": "Der Zusammenhang zwischen Körpergewicht und kortikaler Neuroplastizität und Lernen – eine Pilotstudie", "en": "The relationship between Body Weight and Human Motor Cortical Plasticity and Learning" }, "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": "2025-12-31T01:00:00+01:00", "end_effective": "2026-03-30T02:00:00+02:00", "assignment": "2024-07-10T16:17:43+02:00", "program": null, "subprogram": null, "organization": 14010, "category": 10, "type": 10, "partner_function": 4, "manager": 58643, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 2471 ], "funder_projectcode": "FIF-A 16-0532/2024-0001", "ethics_committee": null, "edudract_number": null, "persons": [ "8294-58643-10" ] }, { "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": 8503, "title": { "de": "„Mikroperfusion der Haut zur Bestimmung von Veränderungen des Mikromilieus der Haut bei SSc“", "en": "Dermal open flow microperfusion to determine changes in the skin microenvironment in vivo during SSc" }, "short": "SSc_OFM", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2024-11-01T01:00:00+01:00", "begin_effective": "2024-11-01T01:00:00+01:00", "end_planned": "2025-12-31T01:00:00+01:00", "end_effective": "2026-12-31T01:00:00+01:00", "assignment": "2024-11-19T13:55:23+01:00", "program": null, "subprogram": null, "organization": 14086, "category": 10, "type": 10, "partner_function": 1, "manager": 120271, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 2296 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "8503-120271-10" ] }, { "id": 8445, "title": { "de": "Wissenschaftspreis der ÖGKJ", "en": "Research Prize of the \"ÖGKJ\"" }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2024-11-01T01:00:00+01:00", "begin_effective": "2024-11-01T01:00:00+01:00", "end_planned": "2027-10-31T02:00:00+02:00", "end_effective": "2027-10-31T02:00:00+02:00", "assignment": "2024-10-15T14:31:21+02:00", "program": null, "subprogram": null, "organization": 14094, "category": 10, "type": 10, "partner_function": 3, "manager": 50907, "contact": null, "status": 2, "research": 10, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 97 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "8445-50907-10" ] }, { "id": 8530, "title": { "de": "Krebsbekämpfung mit digitaler Pathologie ", "en": "Fighting cancer with digital pathology " }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": null, "begin_effective": "2024-12-01T01:00:00+01:00", "end_planned": null, "end_effective": "2026-11-30T01:00:00+01:00", "assignment": "2024-11-26T10:47:29+01:00", "program": 206, "subprogram": null, "organization": 14047, "category": 10, "type": 10, "partner_function": 4, "manager": 92422, "contact": null, "status": 2, "research": 10, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 20 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "8530-92422-10" ] }, { "id": 8591, "title": { "de": "Krebsbekämpfung mit digitaler Pathologie ", "en": "Fighting cancer with digital pathology" }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2024-09-01T02:00:00+02:00", "begin_effective": "2024-12-01T01:00:00+01:00", "end_planned": "2026-08-31T02:00:00+02:00", "end_effective": "2026-11-30T01:00:00+01:00", "assignment": "2025-01-14T13:06:19+01:00", "program": 206, "subprogram": null, "organization": 14020, "category": 10, "type": 10, "partner_function": 4, "manager": 104839, "contact": null, "status": 2, "research": 2, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 20 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "8591-104839-10" ] }, { "id": 8538, "title": { "de": "Mikrobielle Kontaminationen im Tränkewassersystem – Zusammenhang mit Absetzdurchfällen in der Schweinehaltung ", "en": "Microbial contamination in the drinking water pipe system – correlation with post weaning diarrhea in pig farming" }, "short": "MikroWaSta", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2024-11-01T01:00:00+01:00", "begin_effective": "2024-12-01T01:00:00+01:00", "end_planned": "2027-04-30T02:00:00+02:00", "end_effective": "2027-04-30T02:00:00+02:00", "assignment": "2024-12-03T15:10:53+01:00", "program": null, "subprogram": null, "organization": 14023, "category": 10, "type": 10, "partner_function": 4, "manager": 58733, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 957 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "8538-50497-11", "8538-51198-11", "8538-58733-10", "8538-103077-12" ] }, { "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": 8558, "title": { "de": "Teaching students how children with neurodevelopmental disorders adopt and interact with technologies", "en": "Teaching students how children with neurodevelopmental disorders adopt and interact with technologies" }, "short": "TE(A)CHADOPT", "url": null, "abstract": { "de": "Technologien spielen eine immer größer werdende Rolle im Alltag von Kindern mit Entwicklungsstörungen. So werden sie beispielsweise zu Therapiezwecken und als Kommunikationshilfen eingesetzt. Vielfach ist die Barrierefreiheit von Technologien für Kinder mit Entwicklungsstörungen jedoch nicht ausreichend gegeben. Zugleich wird dieses Thema in der Ausbildung derjenigen Studierenden, die in ihrem Berufsleben später Technologien (mit-)entwickeln und/oder einsetzen werden noch kaum behandelt. Im Rahmen dieses interdisziplinären Kooperationsprojekts von sieben Institutionen aus sechs Ländern sollen Leitlinien zur Evaluation von Technologien hinsichtlich ihrer Barrierefreiheit für Kinder mit Entwicklungsstörungen entwickelt und ein umfangreiches Lehrmaterial erstellt, eingesetzt und verbreitet werden. TE(A)CHADOPT soll dazu beitragen, dass Technologien künftig besser die Wünsche und Bedürfnisse von Kindern mit Entwicklungsstörungen erfüllen.", "en": null }, "begin_planned": "2024-10-01T02:00:00+02:00", "begin_effective": "2024-12-15T01:00:00+01:00", "end_planned": "2027-09-30T02:00:00+02:00", "end_effective": "2027-12-14T01:00:00+01:00", "assignment": "2024-12-12T12:09:30+01:00", "program": 220, "subprogram": null, "organization": 14094, "category": 10, "type": 10, "partner_function": 3, "manager": 77049, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 10 ], "funder_projectcode": "2024-1-AT01-KA220-HED-000248380", "ethics_committee": null, "edudract_number": null, "persons": [ "8558-50573-12", "8558-79651-12", "8558-91531-12", "8558-77049-10" ] }, { "id": 8299, "title": { "de": "Energetik-Transkriptions Kopplung im hypertensiven Herzen", "en": "Energetics-transcription coupling in hypertensive heart" }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2025-01-01T01:00:00+01:00", "begin_effective": "2025-01-01T01:00:00+01:00", "end_planned": "2029-12-31T01:00:00+01:00", "end_effective": "2029-12-31T01:00:00+01:00", "assignment": "2024-07-17T18:19:55+02:00", "program": 110, "subprogram": null, "organization": 14083, "category": 10, "type": 10, "partner_function": 4, "manager": 62747, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "STA 194", "ethics_committee": null, "edudract_number": null, "persons": [ "8299-62747-10", "8299-75758-12", "8299-105142-12", "8299-110709-12", "8299-117943-12", "8299-131037-12", "8299-122231-12" ] }, { "id": 8728, "title": { "de": "Vergleich der konvektive Wasserdampfablation (convective water vapor energy, WAVE™)\r\nmit dem Rezum™-System versus Holmium Laser Enukleation der Prostata (HoLEP) versus\r\nbipolare transurethrale Resektion der Prostata (TUR-P) bei Patienten mit benignen\r\nProstatasyndrom (BPS) – eine randomisierte Studie", "en": "Comparison of Convective Water Vapor Ablation (convective water vapor energy, WAVE™)\r\nwith the Rezum™ System versus Holmium Laser Enucleation of the Prostate (HoLEP) versus\r\nBipolar Transurethral Resection of the Prostate (TUR-P) in Patients with Benign Prostatic\r\nSyndrome (BPS) – A Randomized Study" }, "short": "Vektor", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2025-01-01T01:00:00+01:00", "begin_effective": "2025-01-01T01:00:00+01:00", "end_planned": "2030-12-31T01:00:00+01:00", "end_effective": "2030-12-31T01:00:00+01:00", "assignment": "2025-03-17T15:43:09+01:00", "program": null, "subprogram": null, "organization": 14056, "category": 10, "type": 10, "partner_function": 3, "manager": 121670, "contact": null, "status": 2, "research": 2, "grant": 10, "event": null, "study": 12, "language": null, "funders": [], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "8728-121670-10" ] }, { "id": 8316, "title": { "de": "Uterine Trophoblasteninvasion: Ein mastrixbasiertes 3D-Gefäßmodel zur \r\nCharakterisierung schwangerschaftsassozierter Erkrankungen", "en": "Uterine trophoblast invasion: A mastrix-based 3D vascular model for the characterization of pregnancy-associated diseases" }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2025-01-01T01:00:00+01:00", "begin_effective": "2025-01-01T01:00:00+01:00", "end_planned": "2025-12-31T01:00:00+01:00", "end_effective": "2026-12-31T01:00:00+01:00", "assignment": "2024-07-29T15:26:52+02:00", "program": null, "subprogram": null, "organization": 14017, "category": 10, "type": 10, "partner_function": 2, "manager": 76930, "contact": null, "status": 2, "research": 3, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 135 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "8316-76930-10", "8316-97931-11" ] }, { "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" ] } ] }