Multiple myeloma is an incurable hematological cancer with an unmet need for new therapies. In his doctoral thesis, M.Sc. Muntasir Mamun Majumder has focused on accelerating the adoption of precision medicine practices in myeloma and other hematological cancers. The main goal of his thesis was to identify individualised treatment decisions and to facilitate drug discovery efforts for multiple myeloma.
The thesis covers all the key aspects of precision medicine from method development, patient stratification and biomarker identification to validating the clinical utility of the findings.
Mamun graduated from the Stockholm University in 2010, with a masters in Genetic toxicology. He also has a degree in Pharmacy and he wanted to find a doctoral project where both of these topics could be combined. In 2010 he received a highly competitive FIMM-EMBL PhD student position and was among the first batch of students who started at the rotation programme in 2010.
The FIMM-EMBL program caught my attention. After visiting FIMM for the interview I was totally convinced that FIMM is the place I wanted to be that combines cutting edge science, highly organized doctoral training and importantly an international atmosphere that supports growth of young scientists like me and trust me, I was not wrong then.
- Muntasir Mamun Majumder
Mamun’s thesis project has been conducted in the context of the FIMM’s Individualised systems medicine in cancer (ISM) Grand Challenge programme, under the supervision of Group Leader Caroline Heckman and FIMM-EMBL Group Leader Krister Wennerberg. The thesis is based on three publications, two of which are currently under review. Mamun has, however, significantly contributed to five other related publications that are listed in the thesis and could have been included in it.
During the thesis work, Mamun has developed and implemented a comprehensive platform for precision therapies. The group has assessed responses to more than 140 anticancer therapies in 100 myeloma patient samples and integrated their responses with genomic, transcriptomic, and clinical profiles. This rich pharmacogenetic resource has been the starting point for connecting genetic profiles to drug responses.
Using unsupervised clustering of drug responses Mamun was able to identify four therapeutically relevant myeloma patient subgroups. The subgroups differed not only in response to certain class of drugs, called signal transduction inhibitors, but also in their genomic profile and clinical outcome.
Thanks to the research collaboration with hematologists, four patients were treated with tailored therapies based on preclinical evidence from this study. All of them achieved meaningful and objective clinical responses.
The unbiased screening of a large set of oncology compounds we have performed allowed us to identify drug candidates to be repurposed and guided the off-label use of approved molecules. The clinical responses we saw further increased our confidence in this approach since the results indicated that the responses in the laboratory setting reflect treatment outcome in patients.
In the last manuscript of the thesis, Mamun describes the high-content, multi-parametric flow cytometry assay he developed and utilized to determine the diversity of drug responses in different hematopoietic cell populations.
By testing 11 hematopoietic cell types and 71 small molecules Mamun showed that hematological cell populations exhibit distinct drug responses that are tied to their cellular lineages.
We often forget that the core identity of the cells is very important. It should be considered when studying treatment response since it provides opportunities to obtain a new level of therapy precision.
Outside the lab world, Mamun enjoys travelling, photography and music. He takes great pictures and we at FIMM have been happy to be able to utilize these skills.
Mamun will continue working at FIMM until the next summer to finish his ongoing projects. In the future, he would be interested in closing the circle and returning back to pharmaceutical industry. His thesis work is based on a collaborative research project with a pharma company and he feels that he could contribute a lot to the pharmaceutical R&D work.
My interest in cancer research has always be driven by my personal experiences having a close family member dying of cancer. My goal never was to get a degree, but to get answers to the scientific questions that I had in mind.
The public examination of M.Sc. Muntasir Mamun Majunder’s doctoral dissertation will take place on 12 October at 13:00 in Haartman Institute, Lecture hall 2, Haartmaninkatu 3. Associate Professor Alf Grandien, Karolinska Institute, Sweden, will serve as the opponent, and Professor Liisa Holm as the custos.
The thesis is also available in an electronic format.