PhD Student - ,,lmmunotherapeutic Targeting of Leukemia-lnitiating cells in AML"

at  Universittsklinikum Frankfurt

PART TIME (65% PER WEEK) | LIMITED TO 2 YEARS | ANNOUNCEMENT NUMBER: 469-2024

We are seeking a highly motivated PhD student to join our Leukemia Research Group at the Department of Pediatrics (Director: Prof. Jan-Henning Klusmann) and the Department of Experimental Pediatric Hematology & Oncology (Director: Prof. Dirk Heckl). Our joint labs are at the forefront of pediatric leukemia research, focusing on genetic and epigenetic analyses and pioneering innovative molecularly-guided therapeutic approaches.
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Your role

• Acute myeloid leukemia (AML) development often involves a preleukemic stage, making the prevention of cancer by targeting pre-oncogenic cells a key goal in cancer research. However, these cells are notoriously difficult to define and capture, leading to limited success in preemptive antileukemic therapies to date.
• Our research focuses on myeloid leukemia in children with Down syndrome (ML-DS), which evolves through a stepwise clonal process starting from fetal hematopoiesis and progressing through a preleukemic stage known as transient leukemia (TAM). In 20-30% of cases, TAM progresses to ML-DS following the acquisition of secondary mutations, with GATAl mutant cells persisting despite cytarabine treatment. These minimal residual disease (MRD) cells are critical to the development of ML-DS, making them a prime target for research and therapeutic intervention.
• This PhD project will explore the potential of immunotherapy, an efficient therapeutic option for cancer cell targeting and surveillance, which remains unexplored for TAM and ML-DS. By employing flow cytometry-based cell enrichment followed by single-cell transcriptomics and proteomics, the project aims to characterize persistent clones and develop suitable immunotherapeutic strategies, such as CAR T-cells. These cellular immunotherapeutic approaches will be evaluated using preclinical patient-derived xenograft models.
• The anticipated outcomes of this research will not only enhance our understanding of the stepwise evolution of ML-DS, but will also pioneer the elimination of persisting AML clones through immunotherapy, marking a significant advancement in cancer treatment.

Who you are

• Master’s degree in life sciences or equivalent
• Passion for discovery of novel therapy approaches and epigenetic mechanisms of gene regulation
• Collaborative spirit & good communication skills
• Experience in basic laboratory techniques (i.e. molecular biology, flow cytometry etc.)
• Proficiency in spoken and written English
• Due to legal regulations, valid proof of measles immunity / measles vaccination is required.

What we offer

• Collective agreement: In addition to an attractive salary based on a collective agreement with an annual special payment, you benefit from long-term security through company pension schemes
• Collaborative spirit: Experience in basic laboratory techniques (i.e. molecular biology, flow cytometry etc.), Proficiency in spoken and written English, Excellent scientific environment & dedicated mentoring, Training in novel cutting edge techniques to study epigenetic mechanisms in leukemia cells, Collaboration opportunities with national & international world-leading laboratories, Participation in training and qualification programs of the MSNZ and the Goethe University
• Mobility: Free public transport in all Hessen (Free State Ticket Hessen)
• Campus: Our attractive university hospital campus offers a modern cafeteria, various cafes, and opportunities to rest in numerous green spaces. A walk on the riverside of the Main offers relaxation during breaks
• Work-Life-Balance: Part-time employment is possible, we offer childcare in our daycare center (if you have any questions, please contact Familienservice@ukffm.de), child care during holidays
• Health Promotion: Benefit from our attractive health offers. We offer regular online and face-to-face courses on nutrition, relaxation, sports and exercise.
• Professional development: Internal and external training for your professional development
• Any questions? Many answers can be found in our FAQs for new employees. If you have any further questions, please do not hesitate to contact us.

Women are underrepresented in these positions at the University Hospital Frankfurt. Applications from women are therefore particularly welcome. Disabled applicants are preferred if they have the same personal and professional qualifications.
Join our team
Use the time until July 3, 2024 to apply. Please submit your online application including a possible starting date and your salary expectations. For further information regarding the position and project, please contact Ms. Hugenberg (c.hugenberg@kinderkrebsstiftung-frankfurt.de) or Ms. Kunz (sandra.kunz@ukffm.de)

• Acute myeloid leukemia (AML) development often involves a preleukemic stage, making the prevention of cancer by targeting pre-oncogenic cells a key goal in cancer research. However, these cells are notoriously difficult to define and capture, leading to limited success in preemptive antileukemic therapies to date.
• Our research focuses on myeloid leukemia in children with Down syndrome (ML-DS), which evolves through a stepwise clonal process starting from fetal hematopoiesis and progressing through a preleukemic stage known as transient leukemia (TAM). In 20-30% of cases, TAM progresses to ML-DS following the acquisition of secondary mutations, with GATAl mutant cells persisting despite cytarabine treatment. These minimal residual disease (MRD) cells are critical to the development of ML-DS, making them a prime target for research and therapeutic intervention.
• This PhD project will explore the potential of immunotherapy, an efficient therapeutic option for cancer cell targeting and surveillance, which remains unexplored for TAM and ML-DS. By employing flow cytometry-based cell enrichment followed by single-cell transcriptomics and proteomics, the project aims to characterize persistent clones and develop suitable immunotherapeutic strategies, such as CAR T-cells. These cellular immunotherapeutic approaches will be evaluated using preclinical patient-derived xenograft models.
• The anticipated outcomes of this research will not only enhance our understanding of the stepwise evolution of ML-DS, but will also pioneer the elimination of persisting AML clones through immunotherapy, marking a significant advancement in cancer treatment