POST-DOCTORAL FELLOW IN ACUTE MYELOID LEUKEMIA RESEARCH

03/15/21   France   INSERM U944 - Saint-Louis Research Institute  

Job description

Host team and institute: INSERM U944 - Institut de Recherche Saint-Louis – Genomes and Cell Biology of Diseases. - Website: https://gencelldis.fr/ - Address: Hôpital Saint-Louis - 16, rue de la grange aux belles, 75010, Paris.

Saint-Louis Research Institute was created in 1958 by Jean Bernard and Jean Dausset (Nobel Prize), aiming to achieve excellence in research and teaching, in the fields of hematology, oncology, cell biology, immunology, virology, genetics and therapeutic biotechnologies. Our research institute is located in the center of Paris within the Saint-Louis campus, and benefits from a close relationship and collaboration with Saint-Louis hospital. The institute is affiliated to the doctoral school of “Hematology, Oncology & Biotherapies” and hosts the “European School of Hematology”, thus participating to the training of over 2000 researchers and clinicians every year. Since 2020, Saint-Louis Research Institute is also the home of the ambitious “National Leukemia Institute THEMA”, which seeks to develop public-private partnerships to cure leukemia in 10 years.

Our research unit (UMR U944: genomes, cellular biology & therapeutics), has an internationally recognized research program with world-renowned leukemia researchers, such as Jean Soulier, Hugues de Thé and Alexandre Puissant. Consequently, intellectual interactions among our department members are fostered by a number of weekly research seminars. Our research unit is composed of 6 groups whose research encompasses a broad spectrum of fields, including basic virology, cell biology, cancer genomics, cancer biology and leukemia research, yeast biology, functional studies of post-translational modifications and chromosome biology. Most of the studies carried out by our team bridge several of those fields and have implications in translational research, together with the clinical groups of Saint-Louis hospital. The team works in close partnership with Saint-Louis Hospital Clinical Investigations Center (INSERM-CIC 1427) to accelerate the clinical translation of our lab discoveries. Our team also benefits from a privileged access to a large variety of institutional core facilities, including a fully equipped animal facility, a Fluorescence Activated Cell Sorting and flow cytometry facility, a sequencing facility, and an imaging facility.

Available position: An EHA funded two-years post-doctoral position (possible extension of three extra years) will be opened in March 2021 in a young dynamic team led by Dr Lina BENAJIBA, a physician-scientist focusing on target identification and drug discovery in Acute Myeloid Leukemia. 

Project description: Our team develops new translational research strategies focused on the identification of druggable oncogenic targets to pave the road for successful acute myeloid leukemia (AML) treatment. The post-doctoral fellow will seek to dissect the key role of the bone marrow (BM) niche in sustaining AML and regulating drug resistance, aiming ultimately to develop concomitant “seeds” and “soil” leukemia targeting strategies to improve patients’ prognosis. Novel niche-leukemic crosstalk-induced dependencies will be unraveled using high-throughput functional screening methods in an ectopic humanized BM-AML organoid specifically engineered for large scale target discovery. He/she will then shed light on the mechanistic underpinnings of the BM-leukemia crosstalk using transcriptomic-, epigenomic- and microscopy-based approaches.

Selected publications:

1. Roux B*, Vaganay C*, Vargas JD, Alexe G, Benaksas C, Pardieu B, Fenouille N, Ellegast JM, Malolepsza E, Ling F, Sodaro G, Ross L, Pikman Y, Conway AS, Tang Y, Wu T, Anderson DJ, Le Moigne R, Zhou HJ, Luciano F, Hartigan CR, Galinsky I, DeAngelo DJ, Stone RM, Auberger P, Schenone M, Carr SA, Guirouilh-Barbat J, Lopez B, Khaled M, Lage K, Hermine O, Hemann MT, Puissant A, Stegmaier K, and Benajiba L. Targeting AML dependency on VCP-mediated DNA repair through a selective second-generation small molecule inhibitor. Sci Transl Med. 2021; in press.

2. Su A, Ling F, Vaganay C, Sodaro G, Benaksas C, Dal Bello R, Forget A, Pardieu B, Lin KH, Rutter JC, Bassil CF, Fortin G, Pasanisi J, Antony-Debré I, Alexe G, Benoist JF, Pruvost A, Pikman Y, Qi J, Schlageter MH, Micol JB, Roti G, Cluzeau T, Dombret H, Preudhomme C, Fenouille N, Benajiba L, Golan H, Stegmaier K, Lobry C*, Wood KC*, Itzykson R*, Puissant A*. The folate cycle enzyme MTHFR is a critical regulator of cell response to MYC-targeting therapies. Cancer Discov. 2020;Dec;10(12):1894-1911.IF 26.4

3. Benajiba L, Alexe G, Su A, Raffoux E, Soulier J, Hemann MT, Hermine O, Itzykson R, Stegmaier K and Puissant A. Creatine kinase pathway inhibition alters GSK3 and WNT signaling in EVI1-positive AML. Leukemia. 2019;33:800-804. IF 9.9

4. Benajiba L*, Wagner FF*, Campbell AJ, Weiwer M, Sacher JR, Gale JP, Ross L, Puissant A, Alexe G, Conway A, Back M, Pikman Y, Galinsky I, DeAngelo DJ, Stone RM, Kaya T, Shi X, Robers MB, Machleidt T, Wilkinson J, Hermine O, Kung A, Stein AJ, Lakshminarasimhan D, Hemann MT, Scolnick E, Zhang YL, Pan JQ, Stegmaier K and Holson EB. Exploiting an Asp-Glu \"switch\" in glycogen synthase kinase 3 to design paralog-selective inhibitors for use in acute myeloid leukemia. Sci Transl Med. 2018;10. IF 17.2

5. Fenouille N*, Bassil CF*, Ben-Sahra I, Benajiba L, Alexe G, Ramos A, Pikman Y, Conway AS, Burgess MR, Li Q, Luciano F, Auberger P, Galinsky I, DeAngelo DJ, Stone RM, Zhang Y, Perkins AS, Shannon K, Hemann MT, Puissant A and Stegmaier K. The creatine kinase pathway is a metabolic vulnerability in EVI1-positive acute myeloid leukemia. Nat Med. 2017;23:301-313. IF 30.6

Requirements

Requirements: We are looking for a highly motivated and dynamic fellow wishing to complete his post-doctoral training in a young and international team, hosted by an internationally renowned INSERM Unit. The candidate must appreciate teamwork, have good interpersonal skills and be rigorous and organized in his/her work. Experience in molecular/cellular biology and murine models is required. Experience in in vivo imaging would be an asset. Applicants should hold a PhD degree in Biochemistry, Cellular Biology, Molecular Biology, Oncology, Hematology or related disciplines (or have recently submitted their thesis with scheduled defense) and have published (or about to publish) in a peer reviewed journal.

How to apply

Applications must be sent to lina.benajiba@inserm.fr as a single PDF file including:

- Cover letter explaining the candidate’s interest in joining the lab and his/her future career development expectations (max 1 page).

- Curriculum Vitae including academic track, main technical skills, main past achievements and scientific productions.

- Contact details of three past supervisors who can be contacted for recommendation letters.