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PhD Defence Interview - Taha Sen

Taha Sen and the cover of his thesis
The cover of Taha Sen's thesis is inspired by Pink Floyd and cell sorting. He defends his thesis on the 17th of November.

Taha Sen’s PhD thesis focus on the life span of red blood cells and elucidates the important role of mitochondria. He is defending his thesis on the 17th of November and in this interview he gives us an overview of his results as well as what it’s been like being a doctoral student during a pandemic.

Can you tell us about the research during your PhD?

I’ve been focusing my thesis work on the life span of red blood cells. More specifically I’ve been unraveling the role of mitochondria during erythropoiesis, i.e. the formation of red blood cells. 

The underlying study for my thesis was performed by my initial main supervisor, Sofie Singbrant, during her postdoctoral work in 2008. She was working with a mouse model of anemia (pRb knock-out mice) that resembles human Myelodysplastic syndromes (MDS), which is a heterogenous hematopoietic disorder where about 80% of the patients are anemic, making it one of the most characteristic MDS symptoms. Sofie and her colleagues showed that the ineffective erythropoiesis in these mice was due to cell cycle defects and revealed that mitochondria related genes were downregulated - and that’s where my first study began. We wanted to answer the outstanding question of at what stage erythropoiesis was perturbed and identify the connection between cell cycle and mitochondrial function. By using an improved FACS strategy, we showed that the developmental block occurs at the cell cycle exit and that Pgc1b, a co-activator of mitochondrial biogenesis, was downregulated specifically at this stage. We were able to restore erythropoiesis in the pRb deficient mice by overexpressing Pgc1b, as well as by drugs affecting the same transcriptional complex, showing that the mitochondrial function is crucial for the formation of mature red blood cells.

In the second study, we translated our data from the first study into human cells by reducing the expression of PGCR1b in human HSC (hematopoietic stem cells). We discovered a developmental block in erythropoiesis similar to what we had seen the pRb deficient mice and MDS patients. When we looked closer into specific erythroid populations we saw huge effects on the cell cycle and, just like in the first study, the progenitors failed to exit. Interestingly, a subgroup of MDS patients have a chromosomal deletion including PGC1b called del(5q)MDS. Ideally our results would translate into the clinic where these drugs could potentially help this subgroup of MDS patients. The drug is actually already used in the clinic for various metabolic diseases, which means it’s already approved to be used in humans.
Unfortunately, the pandemic put a stop to the follow up of this study. It was difficult to obtain bone marrow before, but now it’s impossible. So, sadly patient samples are out of the picture for now. 

The third study remained in the field of erythropoiesis where we looked into the gene Ypel4 that’s highly and specifically expressed in red blood cells upon late maturation stages, but has been overlooked in the field. Although highly expressed, a knockout hardly gives any phenotype on peripheral blood values. Instead, what we discovered was that this gene is crucial for the clearance of old red blood cells. Without this gene, the cells lose the typical red blood cell shape and membrane integrity which affects their mechanistic properties, e.g. reducing their flexibility, which leads to an increased clearance and turnover rate of the cells.

How did you end up doing a PhD in Lund?

I’m born and raised in Malmö and studied at Lund university. During my studies I applied and was accepted into the Stem cell school in 2014 which prepared me to start a PhD. It was mainly two SCC labs that I really wanted to go to and when Sofie pitched the idea about the role of mitochondria in erythropoiesis and blood production, I was sold. 

What has been the most challenging aspect of your PhD?

I will have to say the battle with myself… It’s not always easy to overcome those challenging periods when nothing seems to go your way and when the FACS machine breaks down in the middle of the night, for the third time, I have asked myself “What am I doing here? Is this where I give up?”. But then you get some good results and you happily keep going.

Another challenge was that halfway through my PhD my main supervisor at the time, Sofie Singbrant, got headhunted by the Novo Nordisk Foundation. Although she stayed very involved in the supervision, it was a big change being supervised on a distance. Eventually Johan Flygare, whom we had regular data meetings with, took me under his wing and it was a natural progression for him to become my new main supervisor.

Needless to say perhaps, but the general distance work and digital meetings during the pandemic has not made my doctoral studies easier. We all need on site supervision and to meet up with colleagues. I realized I really missed the impromptu meetings in the corridors of A12, to quickly be able to run something by your supervisors.

Which aspects of your PhD have you found the most valuable?

I’m not saying this as a paid collaboration with the SCC, but I have to say the environment I have been in by working at the Lund SCC and being part of the Research school. We’re constantly offered a fantastic buffet of courses, seminars and workshops, and I know this is not the case elsewhere – we’re so spoilt here.

I’ve also really enjoyed working at A12 and gotten to meet big juggernauts of the stem cell field and learned to build and understand the importance of international collaborations. 

Tell me about the cover of your thesis?

The many hours in front of the FACS machine made me want to visualize the differentiation of hematopoietic stem/progenitor cells into red blood cells while they go through the FACS. I wanted to illustrate the FACS with a prism, which brought one of Pink Floyd’s best albums “The dark side of the moon” to mind, where white light hits a prism that splits it up into a rainbow. I thought to myself “I might be able to combine them” and I think they just blend together perfectly. 

What are your future plans?

I decided pretty early, around my half time, that I probably wasn’t going to do a postdoc and I’m still 99% sure I’m not doing postdoc…don’t get me wrong, I respect and admire people that wants to continue in academia, but it’s not for me. 

I do thrive in a research intense environment, so I will look into other possibilities where I can continue with research in the industry available in the Öresund region. I’m excited to try something new.

What you like to do when you are not researching?

I have 4 main interest outside research:

Food – I like to explore fusion cooking.

Gardening – Right now I have something resembling an indoor garden in my apartment, but can’t wait to have a small patio or garden. 

Computer games – That’s how I unplug from work, so the many hours I spend in front of my games are worth it.

Music – I listen and collect almost anything that I can relate to and have maybe 400-500 vinyl records containing everything from Bebop jazz to Black sabbath.

 

 

Taha Sen will be defending his PhD thesis “Elucidating the regulators of red blood cell development in health and disease” on Wednesday the 17th of November at 1.00 pm in I1345, BMC, Lund.

Click here for the Zoom link

His opponent is Professor James Palis, University of Rochester Medical Center, USA.