eRapport

Translational Development of Preclinical Models and Therapies in Haematological Malignancies and Cancer

Prosjekt
Prosjektnummer
911884
Ansvarlig person
Emmet Mc Cormack
Institusjon
Helse Bergen HF
Prosjektkategori
Forskningsprosjekt
Helsekategori
Blood, Cancer
Forskningsaktivitet
1. Underpinning, 5. Treatment Developement
Rapporter
2016 - sluttrapport
Translational Development of Preclinical Models and Therapies in Haematological Malignancies and Cancer Technological advances in genomics and proteomics has unearthed many new candidate targets in a wide variety of cancers, however, the methods employed to authenticate these prospective targets in vivo tend to be quite protracted. In vivo validation and preclinical testing remain the rate-limiting steps in translating these treatments to the clinic. The 5-year survival for metastatic cancers has changed little in the last two decades and while molecular targeted therapies have provided some recent promise, the clinical impact upon survival has been limited. Technological advances in genomics and proteomics has unearthed many new candidate targets in a wide variety of cancers, however, the methods employed to authenticate these prospective targets in vivo tend to be quite protracted. In vivo validation and preclinical testing remain the rate-limiting steps in translating these treatments to the clinic. There is an essential need to integrate in vivo imaging, imaging agents and gene vectors to accelerate preclinical validation of novel nanomedicines and drugs in relevant preclinical models. Our understanding of malignant disease pathogenesis has to a large extent been derived from several decades of research on human subjects.4 However, experimental insight into the preliminary events of cancer before they become clinically perceptible is unfeasible in human subjects. Thus, the use of animal models of cancer serves the function of making the disease accessible to experimentation impossible in human patients, with the objective of the experimental approach to extend the knowledge of disease pathogenesis and development of new therapeutic regimes.5 While a plethora of different models exist for cancer, genetic models are particularly vogue. However, while these models are useful in determining the multi-step evolution of metastasis, their contribution to the translational development of therapeutics has been limited. We propose that the development of primary patient xenografts of cancer and complimentary in vivo imaging strategies may give greater insight into the molecular basis of these diseases. Subsequently, this modelling strategy will permit more accurate translational drug development. There is an essential need to integrate in vivo imaging, imaging agents and gene vectors to accelerate preclinical validation of novel nanomedicines and drugs in relevant preclinical models. STATUS: In total this project has resulted in the successful defence of 1 PhD student and publication of 22 original articles, including one highlight paper in Cell Stem Cell. Further works are still in progress and a further 5-8 papers can be anticipated over the next 2 years resulting from this funding. The preclinical works from this project have set the foundations for multiple applications for clinical trial at Haukeland Univeristy Hospital. 2 further PhD candidates (Shafiee and Stigen) are anticipated to complete in the coming 2 years. Subsequent to the results from this project the PI has won a Marie Curie ITN (2 PhD students), is workpackage leader of H2020 grant on the development of a novel AML vaccine where novel immunocompetent PDX model of AML will be developed, in addition to securing an Cancer Society 4 year grant to continue this work on Myeloid malignancy, NFR FRIPRO grant to explore development of novel PDX models of Pancreatic cancer and sonoporation and NOVO funding to develop a novel therapy for AML/MDS. As a direct consequence of the results generated from this project we have set the foundation for a number of novel therapeutic applications. in addition to the results published (and reported herein) there are a number of works that are still underway with clinical potential. Indeed, Our ethical approved (REK 2015/543) clinical phase I trial in refractory/relapsed AML will include patients with repurposed medicine mepacrin (quinacrin) plus valproic acid combination, based on extensive preclinical experiment (directly resulting form this project) suggesting effect in resistant/complex karyotype clones. Two off-label treated pilot patients (CMML-2/AML, relapsed/refractory AML) have experienced more than two months stable disease on mepacrine (100-300 mg per day) plus valproic acid (300 mg+600 mg per day). Our preclinical data suggest effective therapeutic effect in mouse human cell line xenografts, and this combination seems to specifically targeting intracellular signalling pathways. This trial introduces therapy guidance based on the clonal picture of the patient. Characterization and avatars will be created from bone marrow by patients included for co-clinical trial. IN our continuing collaboration with Sonia Lain at Karolinska, we have resubmitted a final version of our work looking at DHODH inhibition to the prestigious journal Cancer Cell. Should this work be accepted, it will provide the basis of a whole new set of drugs for clinical development in AML. In collaboration with Caroline Heckmanns group in Helsinki, we have developed a novel combination of Kinase inhibitors in AML. This paper (resubmitted to Blood December 2016) will set the foundations of a novel clinical trial targeting the supporting stroma of AML. Redevelopment of the nucleoside analogue Elacytarabine, received funding from Novo Exploratory preseed grant and is currently under preclinical redevelopment employing the techniques (PET/CT imaging of AML with FLT) as described in this application. Results are promising and further funding will be sought this year to re-enter the clinic in a Phase II trial of Elacytarabine Vs Cytarabine. Redevelopment of this drug will render a new drug in the compliment for the treatment of AML. Finally, the remarkable work of PhD research Shafiee (PhD stipend - Helse vest) has resulted in the development of several new models of MDS (unpublished results) incuding patient derived xenografts models which will better replicate the patients disease state. These models were made possible through the use of the MDS biobank generated by Kittang. Furthermore she has been able to develop novel therapeutic combinations of drugs which are directly relevant to the clinic and monitored by novel imaging technologies described in this project. the funding received in this project has heavily subsidised the expenses of Shafiees work, and as such Shafiee has requested transfer of funds to 2017. I highly support this recommendation.
2015
Technological advances in genomics and proteomics has unearthed many new candidate targets in a wide variety of cancers, however, the methods employed to authenticate these prospective targets in vivo tend to be quite protracted. In vivo validation and preclinical testing remain the rate-limiting steps in translating these treatments to the clinic.The 5-year survival for metastatic cancers has changed little in the last two decades and while molecular targeted therapies have provided some recent promise, the clinical impact upon survival has been limited. Technological advances in genomics and proteomics has unearthed many new candidate targets in a wide variety of cancers, however, the methods employed to authenticate these prospective targets in vivo tend to be quite protracted. In vivo validation and preclinical testing remain the rate-limiting steps in translating these treatments to the clinic. There is an essential need to integrate in vivo imaging, imaging agents and gene vectors to accelerate preclinical validation of novel nanomedicines and drugs in relevant preclinical models. Our understanding of malignant disease pathogenesis has to a large extent been derived from several decades of research on human subjects.4 However, experimental insight into the preliminary events of cancer before they become clinically perceptible is unfeasible in human subjects. Thus, the use of animal models of cancer serves the function of making the disease accessible to experimentation impossible in human patients, with the objective of the experimental approach to extend the knowledge of disease pathogenesis and development of new therapeutic regimes.5 While a plethora of different models exist for cancer, genetic models are particularly vogue. However, while these models are useful in determining the multi-step evolution of metastasis, their contribution to the translational development of therapeutics has been limited. We propose that the development of primary patient xenografts of cancer and complimentary in vivo imaging strategies may give greater insight into the molecular basis of these diseases. Subsequently, this modelling strategy will permit more accurate translational drug development. There is an essential need to integrate in vivo imaging, imaging agents and gene vectors to accelerate preclinical validation of novel nanomedicines and drugs in relevant preclinical models. STATUS: Development work continues on novel imaging contrast agents and therapies. Of note Stigen and Børve Lund et al. (EMIM and WMIC 2015) describes the use of novel NTRo imaging reporter gene system, whilst Jalon et al. describes novel imaging probes to visualise this reporter gene system. Kotopoulis et al. Describes the novel use of sonoporation for the treatment of Pancreatic cancer both preclinically and clinically. Leitch et al (OncoTarget accepted 2016) report the repurposing and sequential treatment of patient derived xenografts of AML with Valproic acid and Hydroxyurea, 2 clinical used drugs. Mamaeva et al (Accepted in Mol. Therapeutics 2016) describes the novel imaging, application and treatment of breast cancer xenografts with a novel nano-particle formulations. Lain et al. (submitted Cell 2016) describes a novel DHODH inhibitor combined with a tyrosine kinase inhibitor in melanoma and CML. Subsequent to the results from this project the PI has won a Marie Curie ITN, is workpackage leader of H2020 grant on the development of a novel AML vaccine where novel immunocompetent PDX model of AMl will be developed, in addition tosecuring an NFR FRIPRO grant to explore development of novel PDX models of Pancreatic cancer and sonoporation.
2014
I denne rapporten fokuserer vi på hovedresultat fra årets forskning, en artikkel publisert i Cell Stem Cell. Teksten under var publisert i Aftenposten oktober 2014 og finnest på linken: http://www.aftenposten.no/viten/Egne-stamceller-kan-gi-din-helt-unike-kreftmedisin-7742247.htmlTradisjonell kreftbehandling er brutal. Den ryster kroppen i grunnvollene, kan gi voldsomme bivirkninger og kanskje ha null effekt på selve kreftsvulsten. Nå jobber kreftforskere over hele verden med ett felles mål – skreddersydd behandling til hver enkelt pasient. Der vi før skjøt med hagle, skal vi nå bli skarpskyttere som treffer. Rent og raskt. Mest mulig effektivt, minst mulig bivirkninger. - Beklager, det er blodkreft La oss ta akutt myelogen leukemi, AML. Det er den vanligste og farligste formen for blodkreft, for mange er beskjeden en ren dødsdom. Dette er en sykdom som oftest rammer de over 60 år, en gruppe som de neste årene bare vil øke. Mange fler vil dermed få denne diagnosen. Grunnen til at AML er så farlig, er fordi sykdommen fins i stamcellene. Stamceller er en type moderceller som konstant lager nye celler, det være seg blodceller eller beinmarg. Eller andre celler. Kreft-stamceller kan dermed pøse ut nye kreftceller, og de lar seg ikke knekke så lett. Tradisjonell kreftbehandling som kjemoterapi kan tvert i mot gjøre dem resistente mot medisinen. Og kreft-stamceller som er immune mot behandling, det er mildt sagt skummelt. Færre enn hver femte AML-pasient overlever dagens behandling. Forskere har funnet et fellestrekk ved den pasientgruppen som har aller dårligst sjanse til å overleve AML. Tre av ti pasienter har en spesiell genmutasjon, Flt3. Ved hjelp av en enkelt blodprøve kan vi altså kartlegge pasientens gener, og se om de har mutasjonene som gjør behandlingen ekstra vanskelig. Men hvordan skal man redde livet til disse menneskene? Vi vet at enkelte typer kreftmedisin virker på noen, og ikke på andre. Problemet er ofte at vi ikke har tid til å teste ut et utall ulike medikament, for i mellomtiden sprer kreften seg og gjør pasienten sykere. Til slutt er det for sent. For pasientgruppen med Flt3-mutasjonen oppdaget forskere ved Det medisinsk-odontologiske fakultet, Universitetet i Bergen, at det faktisk var en spesiell type medisin som virket. Siden en kreftpasient er i tidsnød når det gjelder rett behandling, så ble det viktig å kartlegge genmaterialet deres kjapt. Vårt neste steg var å lage såkalte avatarer. Vi hentet ut pasientens egne kreft-stamceller ved hjelp av en kjapp blodprøve. Deretter ble disse stamcellene sprøytet inn i flere mus. Da utvikler kreften seg på nøyaktig samme måte som i pasienten – bare raskere. Dermed kan vi teste ulike behandlinger og medisiner for å se hvilken som hadde effekt på akkurat denne pasientens type gener og stamceller. Dette ble gjort ved hjelp av avansert bildebehandling utviklet ved UiB til å detektere kreft-stamceller. Med denne teknologien kan man i praksis se hvor og når kreften sprer seg, mens den gjør det. Musene ble avatarer, som kjapt avdekket hvilken skreddersydd behandling som fungerte. Når vi visste det, var det bare å sette i gang samme behandling på den syke pasienten. Vi som forsker på dette, er overbevist om at skreddersydd, personlig kreftmedisin er vanlig om 10 – 15 år. Ved hjelp av genetisk kartlegging, avatarer, avansert bildebehandling og stadig mer kunnskap om kreft, vil flere overleve den fryktede sykdommen. En ny måte å tenke om kreft er på trappene. Dermed kan dine egne stamceller i fremtiden også bli din redning mot kreftsykdommen.
Vitenskapelige artikler
Andresen V, Erikstein BS, Mukherjee H, Sulen A, Popa M, Sørnes S, Reikvam H, Chan KP, Hovland R, McCormack E, Bruserud Ø, Myers AG, Gjertsen BT

Anti-proliferative activity of the NPM1 interacting natural product avrainvillamide in acute myeloid leukemia.

Cell Death Dis 2016 Dec 01;7(12):e2497. Epub 2016 des 1

PMID: 27906185

Dimcevski G, Kotopoulis S, Bjånes T, Hoem D, Schjøtt J, Gjertsen BT, Biermann M, Molven A, Sorbye H, McCormack E, Postema M, Gilja OH

A human clinical trial using ultrasound and microbubbles to enhance gemcitabine treatment of inoperable pancreatic cancer.

J Control Release 2016 Dec 10;243():172-181. Epub 2016 okt 12

PMID: 27744037

Bojan A, Berindan-Neagoe I, Ciurea S, Dima D, Fuji S, Ghiaur G, Grewal R, McCormack E, Tanase A, Trifa A, Tomuleasa C

Proceedings from the 1st Insights in Hematology Symposium, Cluj-Napoca, Romania March 11-12, 2016.

Rom J Intern Med 2016 Sep 01;54(3):157-160.

PMID: 27658163

Helland Ø, Popa M, Bischof K, Gjertsen BT, McCormack E, Bjørge L

The HDACi Panobinostat Shows Growth Inhibition Both In Vitro and in a Bioluminescent Orthotopic Surgical Xenograft Model of Ovarian Cancer.

PLoS One 2016;11(6):e0158208. Epub 2016 jun 28

PMID: 27352023

Suliman S, Mustafa K, Krueger A, Steinmüller-Nethl D, Finne-Wistrand A, Osdal T, Hamza AO, Sun Y, Parajuli H, Waag T, Nickel J, Johannessen AC, McCormack E, Costea DE

Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes.

Biomaterials 2016 Jul;95():11-21. Epub 2016 apr 6

PMID: 27108402

Mamaeva V, Niemi R, Beck M, Özliseli E, Desai D, Landor S, Gronroos T, Kronqvist P, Pettersen IK, McCormack E, Rosenholm JM, Linden M, Sahlgren C

Inhibiting Notch Activity in Breast Cancer Stem Cells by Glucose Functionalized Nanoparticles Carrying ?-secretase Inhibitors.

Mol Ther 2016 May;24(5):926-36. Epub 2016 feb 26

PMID: 26916284

Leitch C, Osdal T, Andresen V, Molland M, Kristiansen S, Nguyen XN, Bruserud Ø, Gjertsen BT, McCormack E

Hydroxyurea synergizes with valproic acid in wild-type p53 acute myeloid leukaemia.

Oncotarget 2016 Feb 16;7(7):8105-18.

PMID: 26812881

Gelebart P, Popa M, McCormack E

Xenograft Models of Primary Acute Myeloid Leukemia for the Development of Imaging Strategies and Evaluation of Novel Targeted Therapies.

Curr Pharm Biotechnol 2016;17(1):42-51.

PMID: 26278528

Suliman S, Parajuli H, Sun Y, Johannessen AC, Finne-Wistrand A, McCormack E, Mustafa K, Costea DE

Establishment of a bioluminescence model for microenvironmentally induced oral carcinogenesis with implications for screening bioengineered scaffolds.

Head Neck 2016 Apr;38 Suppl 1():E1177-87. Epub 2015 aug 14

PMID: 26275210

Sulen A, Gullaksen SE, Bader L, McClymont DW, Skavland J, Gavasso S, Gjertsen BT

Signaling effects of sodium hydrosulfide in healthy donor peripheral blood mononuclear cells.

Pharmacol Res 2016 Nov;113(Pt A):216-227. Epub 2016 aug 16

PMID: 27543462

Gavasso S, Gullaksen SE, Skavland J, Gjertsen BT

Single-cell proteomics: potential implications for cancer diagnostics.

Expert Rev Mol Diagn 2016;16(5):579-89. Epub 2016 mar 21

PMID: 26895397

Engen CB, Hajjar E, Gjertsen BT

Development of Personalized Molecular Therapy for Acute Myeloid Leukemia.

Curr Pharm Biotechnol 2016;17(1):20-9.

PMID: 26420051

Haldorsen IS, Popa M, Fonnes T, Brekke N, Kopperud R, Visser NC, Rygh CB, Pavlin T, Salvesen HB, McCormack E, Krakstad C

Multimodal Imaging of Orthotopic Mouse Model of Endometrial Carcinoma.

PLoS One 2015;10(8):e0135220. Epub 2015 aug 7

PMID: 26252891

Vorobyeva AG, Stanton M, Godinat A, Lund KB, Karateev GG, Francis KP, Allen E, Gelovani JG, McCormack E, Tangney M, Dubikovskaya EA

Development of a Bioluminescent Nitroreductase Probe for Preclinical Imaging.

PLoS One 2015;10(6):e0131037. Epub 2015 jun 25

PMID: 26110789

Sandtorv AH, Leitch C, Bedringaas SL, Gjertsen BT, Bjørsvik HR

4-Alkylated Silver-N-Heterocyclic Carbene (NHC) Complexes with Cytotoxic Effects in Leukemia Cells.

ChemMedChem 2015 Sep;10(9):1522-7. Epub 2015 aug 6

PMID: 26250720

Hampson Peter, Wang Keqing, Ersvær Elisabeth, McCormack Emmet, Schüler Julia, Fiebig Heinz-Herbert, Gjertsen Bjørn Tore, Bruserud Øystein, Lord Janet M

Up-regulation of anti-apoptotic genes confers resistance to the novel anti-leukaemic compound PEP005 in primary AML cells.

Oncoscience 2014;1(8):529-39. Epub 2014 aug 6

PMID: 25594060

Li Ling, Osdal Tereza, Ho Yinwei, Chun Sookhee, McDonald Tinisha, Agarwal Puneet, Lin Allen, Chu Su, Qi Jing, Li Liang, Hsieh Yao-Te, Dos Santos Cedric, Yuan Hongfeng, Ha Trung-Quang, Popa Mihaela, Hovland Randi, Bruserud Oystein, Gjertsen Bjørn Tore, Kuo Ya-Huei, Chen Wenyong, Lain Sonia, McCormack Emmet, Bhatia Ravi

SIRT1 activation by a c-MYC oncogenic network promotes the maintenance and drug resistance of human FLT3-ITD acute Myeloid Leukemia stem cells.

Cell Stem Cell 2014 Oct 2;15(4):431-46.

PMID: 25280219

Haaland Ingvild, Opsahl Jill A, Berven Frode S, Reikvam Håkon, Fredly Hanne K, Haugse Ragnhild, Thiede Bernd, McCormack Emmet, Lain Sonia, Bruserud Oystein, Gjertsen Bjørn Tore

Molecular mechanisms of nutlin-3 involve acetylation of p53, histones and heat shock proteins in acute myeloid leukemia.

Mol Cancer 2014;13():116. Epub 2014 mai 21

PMID: 24885082

Helland Oystein, Popa Mihaela, Vintermyr Olav K, Molven Anders, Gjertsen Bjørn Tore, Bjørge Line, McCormack Emmet

First in-mouse development and application of a surgically relevant xenograft model of ovarian carcinoma.

PLoS One 2014;9(3):e89527. Epub 2014 mar 4

PMID: 24594904

Kotopoulis Spiros, Delalande Anthony, Popa Mihaela, Mamaeva Veronika, Dimcevski Georg, Gilja Odd Helge, Postema Michiel, Gjertsen Bjørn Tore, McCormack Emmet

Sonoporation-enhanced chemotherapy significantly reduces primary tumour burden in an orthotopic pancreatic cancer xenograft.

Mol Imaging Biol 2014 Feb;16(1):53-62.

PMID: 23877869

Zeisig Bernd B, So Chi Wai Eric

A knockout Combo: eradicating AML Stem Cells with TKI plus SIRT1 inhibition.

Cell Stem Cell 2014 Oct 2;15(4):395-7.

PMID: 25280212

Gullaksen SE et al

Single-cell immune signatures? in patients with chronic phase chronic myeloid leukemia (CML) treated with nilotinib

ESH, 2015

Mihaela Popa, Cecilie Brekke Rygh, Tom Christian Holm Adamsen ,Pascal Gelebart, Emmet McCormack

Imaging Myeloid Malignancies with the Proliferation Marker 18F-FLT in Patient Derived Xenograft Models

CCBIO annual meeting, Solstrand, Bergen, 2015

Kjetil Børve Lund, Endre Stigen, Elvira García de Jalón, Mihaela Popa, Cecilie Brekke Rygh, Tom Christian Holm Adamsen, Ole Heine Kvernenes, Bengt Erik Haug and Emmet McCormack

In vivo imaging of a nitroreductase reporter gene with 18F-FMISO

EMIM, Tubingen, Germany, 2015

Kjetil Børve Lund, Endre Stigen, Elvira García de Jalón, Mihaela Popa, Cecilie Brekke Rygh, Tom Christian Holm Adamsen, Ole Heine Kvernenes, Bengt Erik Haug and Emmet McCormack

Preclinical PET/CT imaging of a nitroreductase reporter gene with 18F-­- FMISO

WMIC, Honolulu, Hawaii, USA, 2015

Veronica Mamaeva, Tina Pavlin, John G.Seland, Diadem Seen Karaman, Diti Desai, Sinai Tadayon, Jarmo Teuho, Melanie Ostermann,Jessica Rosenholm, Emmet McCormack.

Gadolinium-incorporated mesoporous silica nanoparticles for MR imaging: long playing contrast agents.

ISMRM, Toronto, Canada, 2015

García de Jalón, E; Lund, K.B; Stigen, E; Mayoral, M; Popa, M; Haug, B E and McCormack, E

Synthetic studies towards nitroreductase-activated fluorescent probes

World Molecular Imaging Congress Honolulu, Hawaii, 2015

García de Jalón, E; Lund, K.B; Stigen, E; Haug, B E and McCormack, E

Synthetic studies towards nitroreductaseactivated fluorescent probes

MedViz Conference, Bergen, Norway, 2015

García de Jalón, E; Lund, K.B; Stigen, E; Haug, B E and McCormack, E

Synthesis of CytoCy5S and its active esters for optical imaging

10th European Molecular Imaging Meeting Tu¨bingen, Germany, 2015)

García de Jalón, E; Lund, K.B; Stigen, E; Haug, B E and McCormack, E

Synthesis of CytoCy5S and its NHS ester for optical imaging

30th Organic Chemistry Winter Meeting Skeikampen, Norway, 2015

Popa, M, Brekke Rygh, C, Holm Adamsen, TC, Gelebart, G, McCormack, E

Imaging Myeloid Malignancies with the Proliferation Marker 18F-FLT in Patient Derived Xenograft Models

CCBIO meetin, Solstrand, Bergen, Norway, 2015

Ingvild Haaland, Jill A Opsahl, Frode S Berven, Håkon Reikvam, Hanne K Fredly, Ragnhild Haugse, Bernd Thiede, Emmet McCormack, Sonia Lain, Øystein Bruserud, Bjørn Tore Gjertsen

Molecular mechanisms of nutlin-3 involve acetylation of p53, histones and heat shock proteins in acute myeloid leukemia

Chemotherapy, 2014

Sahba Shafiee, Jungwoo Lee, Mihaela Popa, Lars Helgeland, Bjørn Tore Gjertsen, Astrid Olsnes Kittang, Biju Parekkadan, Emmet McCormack

Novel pre-clinical models of myelodysplastic syndrome (MDS)

Experimental Hematology, 2014

C Engen, S Eldfors, E Aasebo, A Brendehaug, O Bruserud, SE Gullaksen, R Karjalainen, R Hovland, E Kristoffersen, EM Larsen, MM Majumder, E McCormack, A Parson, T Pemovska, M Popa, F Selheim, A Sulen, C Heckman, BT Gjertsen

CLONAL EVOLUTION IN PRIMARY RESISTANT AML ASSESSED BY GENETIC AND MOLECULAR PROFILING, SINGLE CELL SIGNALLING PROFILING

HAEMATOLOGICA, 2014

BS Tislevoll, C Leitch, M Enger, M Popa, O Bruserud, E McCormack, BT Gjertsen

REPURPOSING PHENOTHIAZINE CHLORPROMAZINE IN THERAPEUTIC TARGETING OF LEUKEMIC STEM CELLS

HAEMATOLOGICA, 2014

Doktorgrader
Øystein Helland

Ovarian Cancer: A Clinical Challenge Requiring Basic Answers

Disputert:
mai 2014
Hovedveileder:
Line Bjørge, Bjørn Tore Gjertsen, Emmet Mc Cormack
Deltagere
  • Veronika Mamaeva Postdoktor
  • Tara Helen Dowling Ph.d.-kandidat
  • Stein-Erik Gullaksen Ph.d.-kandidat
  • Caroline Benedicte Nitter Engen Ph.d.-kandidat
  • Calum Leitch Ph.d.-kandidat
  • Øystein Bruserud Prosjektdeltaker
  • Mihaela Lucia Popa Prosjektdeltaker
  • Bjørn Tore Gjertsen Medveileder
  • Astrid Olsnes Kittang Medveileder
  • Sahba Shafiee Ph.d.-kandidat
  • Zinayida Fandalyuk Prosjektdeltaker
  • Pascal Gelebart Postdoktor
  • Emmet Mc Cormack Prosjektleder
  • Line Bjørge Prosjektdeltaker

eRapport er utarbeidet av Sølvi Lerfald og Reidar Thorstensen, Regionalt kompetansesenter for klinisk forskning, Helse Vest RHF, og videreutvikles av de fire RHF-ene i fellesskap, med støtte fra Helse Vest IKT

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