VACANCIES
Join Mahmoudi Lab
Mahmoudi Lab | Erasmus MC is comprised of an interdisciplinary team and is looking for additional researchers from a variety of backgrounds to fill several open positions. Please Contact Prof. Dr. Tokameh Mahmoudi t.mahmoudi@erasmusmc.nl for more information.
PHD CANDIDATE: PATIENT‐DERIVED MUSCLE INVASIVE BLADDER CANCER ORGANOID (IMMUNO‐ONCOLOGY) PLATFORM FOR DRUG SCREENING AND TREATMENT EVALUATION
Muscle-Invasive Bladder Cancer (MIBC), is treated by one-size-fits-all PreOperative-Chemotherapy (POC) followed by surgical removal of the bladder. Despite this extensive treatment, only 1 of 4 patients benefit from POC, while 75% are exposed to unnecessary toxicity and suffer recurrent/metastatic disease. Immunotherapy holds promise in BC, but is costly and benefits only a small proportion of patients. Thus, there is an unmet need to develop in-vitro platforms that predict MIBC patient response to POC and immunotherapy, enabling selection of the right treatment for the right patient.
Objective and design
MIBC-ORG-IO addresses this caveat by developing a novel MIBC Patient-Derived Organoid (PDO)-T-cell co-culture platform to assess its predictive value for response to different treatment regimens (POC and Immune checkpoint inhibitors (ICIs)). PDOs will also be used to investigate mechanisms underlying treatment response.
Our specific aims:
1. Generate a biobank of 120 MIBC-PDOs and matched T-cells (Tumor-Infiltrating-Lymphocytes (TILs) and/or Peripheral Blood Mononuclear Cells (PBMCs)).
2. Extensively characterize MIBC-PDOs and T-cells via molecular and sequencing approaches.
3. Develop PDO and PDO-T-cell co-culture platforms and readouts for PDO viability and PDO tumour-killing, including immune cell function.
4. Develop robust throughput PDO and PDO-T-cell platform for evaluating organoid predictive response to POC and ICIs.
The tasks for the PhD student with Immunology/molecular biology background will be among others:
Characterize MIBC-derived PDOs at the molecular level (i.e., RNA-seq, whole exome sequencing (WES), HLA-typing, and flowcytometry, immunohistochemistry (IHC) and immunofluorescence (IF) using confocal microscopy. Characterize T-cells (TILs and/or PBMC-derived) at the molecular level by flowcytometry, immune panel profiling and scRNA-seq. Determine optimal conditions to perform MIBC-PDO-T-cell co-culture. Observation of organoid killing using several fluorescent imaging dyes. Determine activation of T-cells by measuring activation markers (CD137, CD154) and secretion of interferon-gamma (IFN-y) using flowcytometry and ELISA.