PhD position: Hematopoietic cancer research and the DNA damage response
- Biochemistry / Molecular Biology
- University of Veterinary Medicine, Vienna
We are looking for a motivated PhD candidate to join the laboratory of Dr. Heidi Neubauer (junior PI in the laboratory of Prof. Richard Moriggl, Functional Cancer Genomics Unit) at the University of Veterinary Medicine, Vienna.
The candidate will commence an ERA PerMed-funded project on 'Investigating the DNA damage response pathway to develop targeted therapies for T-cell cancers with gain-of-function JAK-STAT mutations'.
Mature T-cell leukemias/lymphomas are a group of heterogeneous hematological malignancies of mostly incurable prospects due to limited efficient therapies. The transcription factors STAT3 and STAT5 are effectors of the pro-survival, pro-proliferative JAK-STAT signaling pathway, and hyperactivating gain-of-function (GOF) mutations are found in JAK1/3 or STAT3/5 in human T-cell leukemia/lymphoma patients. STAT3/5 can also influence production of cellular reactive oxygen species (ROS) and the DNA damage response (DDR) pathway, which is often dysregulated in T-cell leukemia/lymphoma patients leading to genomic instability and cancer progression. The aim of this project is to investigate the role of JAK-STAT pathway hyperactivation in regulating the DDR in T-cell leukemia/lymphoma to gain insights into cellular mechanisms of cancer establishment and progression. Additionally, this knowledge will be applied to test novel drug combinations for these diseases, targeting the DDR pathway and/or the JAK-STAT pathway.
To gain novel insights into the involvement of JAK-STAT GOF mutations on the DDR pathway in T-cell leukemia/lymphoma, the PhD candidate will use established model murine and human T-cell leukemia/lymphoma cell lines, implementing various specialized methods to induce and assess DNA damage, ROS production and downstream genomic changes. The candidate will also perform genome editing (CRISPR-Cas9) and will utilize human patient samples and novel pre-clinical mouse models to translate findings and test new therapeutic strategies.
Our laboratory is embedded within a collaborative ERA PerMed Personalized Medicine network, involving multidisciplinary groups from Europe and Canada with skills in clinical practice, drug screening, pre-clinical models, bioinformatics and medicinal chemistry. This network is led by Prof. Satu Mustjoki from the University of Helsinki, Finland. The PhD candidate will become a part of this network and will work closely with our collaborators to acquire patient samples and mouse models, and perform drug screening, which will involve national and international travel.
We are seeking a highly motivated individual with training in biology, molecular biology or biochemistry (M.D. or M.Sc. degree). Evidence of successful previous laboratory work experience (letter of reference) is essential. Any experience in protein biochemistry, mouse work and/or drug screening will be an asset. The successful candidate should have excellent organizational and problem-solving skills, good written and oral English communication skills, and should work well in a team as well as independently.
Salary and working hours:
The successful candidate will be employed according to the salary and working hours for Doctoral candidates as defined by the Austrian Science Fund (FWF): https://www.fwf.ac.at/en/research-funding/personnel-costs/
Please apply via email to: heidi.neubauer(at)vetmeduni.ac.at. Motivated candidates fulfilling the required criteria will be invited for an interview.
de Araujo ED*, Erdogan F*, Neubauer HA* et al., (2019) Structural and Functional Consequences of the STAT5BN642H Driver Mutation. Nature Communications, 10(1): 2517. doi: 10.1038/s41467-019-10422-7.
Schrader A, Crispatzu G, Oberbeck S et al., (2018) Actionable perturbations of damage responses by TCL1/ATM and epigenetic lesions form the basis of T-PLL. Nature Communications, 9(1):697. doi: 10.1038/s41467-017-02688-6.
Mi T, Wang Z and Bunting KD (2018) The Cooperative Relationship between STAT5 and Reactive Oxygen Species in Leukemia: Mechanism and Therapeutic Potential. Cancers, 10(10): pii E359. doi: 10.3390/cancers10100359.
- Name: Heidi Neubauer