AUTHORS: Dr Sanketh Rampes and Dr Anvarjon Mukhammadaminov
In this series the Medspire team interviews doctors about their career, their specialty, the choices they have made and their advice for doctors and medical students.
Here the subject is Dr Aleksandar Ivetic, a principal investigator of a large lab researching leukocyte recruitment, and also the postgraduate lead for research for the School of Cardiovascular Medicine and Sciences. Dr Ivetic has a strong interest in understanding how immune cells respond to myocardial infarction.
A podcast of this interview is available here:
How did you get to where you are today?
Let me start off with my school background. I didn't do very well at school at all. I was a real tearaway. I didn't do any homework. I have no idea how I actually advanced through academia. From a young age, I had some sad news. It is still probably the saddest news I’ve ever had. My mum passed away when I was 15, and that really reset the focus of my life because I then had to learn some life skills.
It's only then that you realise how much your mum actually did. I ended up not only refocusing my outlook on my education, but also my progress was delayed. I had to retake my ‘O’ levels - today's equivalent of GCSEs - and my ‘A’ levels. I took my ‘A’ levels at a sixth form college, and then applied for a place in a university.
I went to Imperial College. I did biochemistry, a BSc honours, and then after that, a PhD at the Marie Curie Research Institute, which is part of Marie Curie Cancer Care. The Research Institute doesn't exist anymore, but you'll probably know of Marie Curie Cancer Care because they have a large campaign to raise money, and their symbol is a daffodil.
The Marie Curie Research Institute wasn't an academic body, and it needed to affiliate itself with one, so my PhD was actually awarded by the Institute of Cancer Research.
For my PhD I worked on mechanisms of how DNA replicates. When a cell divides, it needs to replicate its contents, and the major organelle that needs to be duplicated is the nucleus. So its DNA needs to be replicated with very high fidelity, and any mutations that occur during this replication process was thought - and still is thought - to be the basis of cancer.
So my PhD was about purifying proteins to work out which were involved in the initiation of DNA replication. I gained a lot of knowledge of protein biochemistry. I then took that knowledge to my first postdoctoral position, which was at the National Institute for Medical Research.
I went to summer school when I was at secondary school, and someone said to me - even back then - that if you're going to go into research, go into immunology. So I took the skills that I acquired from the Marie Curie Research Institute and moved into immunology.
Now, in immunology people are only looking at the surface of immune cells, and not really caring about what goes on beyond the skin of the cell. That's because immunology was really founded on generating, or creating antibodies that could bind to receptors.
Through that approach, you could understand the different immune cell subsets, but no one was really talking about the receptors that the antibodies were binding to, and how they were transducing signals into cells. That was what interested me about immunology.
I then used my protein biochemistry skills and applied them to immunology. I made a discovery while I was there for my first postdoc. Luckily, I was able to go into my second postdoc with this discovery, and I ended up at the Institute of Cancer Research.
I should mention that my first postdoc position was at the National Institute for Medical Research, which is now part of the Crick Institute in King's Cross. My second postdoc position was at the Ludwig Institute for Cancer Research, which at the time was at UCL, and that position allowed me to develop what I had discovered at the National Institute for Medical Research.
With all of that knowledge, I then published a couple of papers. I had a lot of preliminary data. I was able to piece that together into an application to the Wellcome Trust. I submitted an application for a Career Development Award, and was successfully granted one.
Half-a-million pounds for five years, to set up my group back at Imperial College, where I did my undergraduate degree at the National Heart and Lung Institute. So I moved from cancer into cardiovascular.
Those five years were productive, but it was a fixed-term contract and I needed to look for another job. I found a senior lecturer position at King's in 2009, and that's where I am today. I've also recently been promoted to reader. So that's my career path in a whistle-stop tour.
What is your current research, and is there one project in particular that really excites you?
We’ve been looking at how molecules interact with one another in a test tube. Then we've tried to look at how these molecules interact with one another in a cell. We've also looked at cell-to-cell interactions, and specifically, we've been looking at how white blood cells - or leukocytes - interact with endothelial cells, which are basically like a sheet of a single cell monolayer which lines the inner lumen of blood vessels.
Leukocyte endothelial cell interactions are really the first stage of an inflammatory response. This is because typically, circulating white blood cells, in order to address an inflammatory insult, need to migrate out of blood vessels and in towards tissue. And so their interaction with endothelial cells is a really important component in that process.
We've been studying these cell-to-cell interactions for many years. Now we've taken this to an organismal level and are trying to understand how immune cells respond to myocardial infarction, and in venous thrombosis as well.
There are two very good experts within our cardiovascular school, Professor Ajay Shah and Professor Alberto Smith, who work in the fields of myocardial infarction and venous thrombosis respectively.
We've been looking at immune cells and how they behave in these pathologies, and we're also trying to work out how we might suppress immune cell function, in order to alleviate some of these pathologies as well, because they're believed to be driven by white blood cells. If we can suppress the effector function of these white blood cells, we may be able to ameliorate some of these pathologies.
So that's really where our work has taken us to - from molecules, all the way up to animal models of cardiovascular research.
What research questions do you hope to answer?
With respect to myocardial infarction, the biggest challenge we have today is trying to salvage as much of the myocardium as possible when a patient comes into A&E. The idea is that they come in, they're presenting with MI, and what you want to do is give them the right regimen of drugs in order to suppress any further damage of the myocardium.
The reason why you want to do that early on is because we know that patients who suffer myocardial infarction have a higher propensity to develop heart failure in later life. This is due to the way that the heart adapts following myocardial infarction, where it starts to become much larger by overcompensating for the lack of muscle function in the area where the cardiomyocytes have been lost.
So trying to rescue or keep alive the cardiomyocytes within this area at risk is really important. It's believed that leukocytes play a damaging role in this regard, and so if we can work out how to stun these immune cells to prevent any further damage of the myocardium, we may increase survival of these cardiomyocytes, and therefore improve outcomes in patients.
What’s also really exciting, but it’s not part of my research per se, is Mauro Giacca's research, who is at our school to try and kick-start the proliferation of cardiomyocytes following myocardial infarction. Cardiomyocytes are non-regenerative in humans.
That group is trying to work out mechanisms to get them to divide - to proliferate and to fill in the gap that has been created following myocardial infarction - so you can improve the pumping action of the left ventricle and alleviate any chances of developing heart failure in later life.
What's also interesting is that myocardial infarction is very similar to stroke, in the sense that it's a time-critical issue where the more neurons you can salvage - which incidentally, again, are non-regenerative - the better the outcome will be for that patient. So we're hoping to explore that area and find novel targets for therapies.
What are some of the biggest changes that you've witnessed?
Knowledge dissemination has been the biggest change in my time as a researcher, because knowledge, as the saying goes, is power. Power to drive your research. Back when I was a PhD student, the internet was only just emerging.
So when I was at the Marie Curie Research Institute, my access to new articles came in the form of paperback journals, which would arrive at the library. I remember eagerly waiting in this library for those journals to arrive. I would tear through the journal’s plastic wrappers and look through their contents to find out if there was anything interesting that was related to what I was doing.
There was also a paperback book called Current Contents which had really thin paper. It was a small A5-sized book that I think was published weekly, and it had all of the keywords in life sciences. As with a phone directory, it was alphabetised, and you would go to your keyword. You would look for that keyword, run your finger along, and then it would tell you which journal that keyword was in.
You would then have to find the journal within that particular issue period, look up that paper, and find out why the keyword was in there. Sometimes it would be relevant, and other times it would mean absolutely nothing. If it did mean something, you would then take that paperback journal to the photocopier, make a copy of it and then keep it on your bench. And that's how you collected your data, or data from other people's work.
So there’s been a massive change since then. I can be in the lab right now with my student. I can take out my phone, I can say: 'I'm sure blah de blah said this and that’, and literally, within seconds, find the actual paper. This is a massive advancement in knowledge dissemination. Another advancement is the ability to have open-access journals. And now there’s this way of publishing your work before it actually gets accepted in the manuscript, in a platform known as ‘Bio-archive’.
Some might think there is an oversaturation of information, but I believe this is a way in which we can readily access information. And you probably won't have to read every single bit of a paper.
What does your role as the lead for postgraduate research involve?
I'm the postgraduate lead for the School of Cardiovascular Medicine and Sciences. Within that school we've got about 100 PhD and MD students, and I oversee their progress and welfare during the entire course of their PhD or MD.
We've got a ‘mixed bag’ of clinical and non-clinical students. Some are full-time, some part-time, and so they all have various different needs. Some of them spend most of their time in the hospital. Others spend it in a wet lab or a dry lab, doing AI type work. All of them are different, but they all are subjected to progress reporting. It's really important that I get to encourage all of these students to document their progress to make sure that they deliver the best PhD they can.
I also sit at faculty level meetings with other PGR leads from other schools, and there we discuss how we might be able to enhance the student experience within the faculty of life sciences and medicine, and enable our students to deliver the best from their postgraduate degrees.
Since the first lockdown, we obviously wanted to create a community for our PGR students. Many of them felt detached from the school at such an acute changeover in time. One day we were in the lab, and the next we were literally scrabbling around, trying to shut down our labs without losing our cells, and without losing some of our animal lines.
It was a very difficult time, but as a PGR lead, I felt it was really important to build an online forum. Within that online forum was a biweekly event that students could tap into. We would cover different topics, including life stories of scientists, which is exactly what we're doing today - we're covering the successes, as well as the failures of those individuals, so that we can get an understanding of what it's like to go through this rollercoaster ride of existing academia.
We were also keen to have personal development topics as well. We had topics on careers advice, race and racism, research integrity, etc.
My role as PGR lead also meant I was involved in public engagement events. We've done two very large ones, and it’s been super exciting to have winning PhD students involved in them. Essentially, we set up workstations around one of the buildings that the school is housed in, which is the James Black Centre at the Denmark Hill Campus, and we get audiences to cycle through these workstations and to engage with various activities. So there's a lot that we are involved in, and these are just a few examples.
Do you have any tips on successfully managing a team?
It's really important to treat every person in your team as an individual. Your team members are individuals with different needs. The way I manage this, especially with newcomers, is to identify their strengths.
Obviously, I would have taken them on because they had a particular skill they were good at. So when they come in I make sure that they explore that strength within their new environment.
From there, you slowly start to build in new techniques for them.
Communication is key, and so I have lab meetings with my group every Monday morning and Friday evening. The Monday morning meetings are really more about work. Friday evening meetings are also about work, but then we have discussions about what we're getting up to over the weekend and we talk more socially.
We might have a few beers or just a laugh about what we've been doing. Then there will be some follow-up on Monday morning as well, before we start business. We're in a WhatsApp group and we send each other photographs of what we’ve got up to over the weekend, - it's quite sweet.
Communication is key, as is understanding your individuals. I remember when I first started out, managing a team was really difficult because you're not told what to do. I was expecting to be hiring people who were exactly like me, who were really enthusiastic and who had the same desires and skills as me. But actually, you slowly begin to learn that everyone is special, everyone is amazing - and that they are not a mini-me.
What advice would you offer to undergraduate students who are considering applying for a PhD or MD, and a career in research?
I would ask them to think very long and hard about whether they really want to do a PhD or not. A PhD is not an easy thing to do. One piece of advice that I would give is to engage in a master's course.
Nowadays these courses are really good. Look for a master's course that has a practical component or something that will feel like you're doing a little bit of a PhD, and that will give you some insight into what it might be like for three years.
We host a cardiovascular master's course and there's a six-month component for being in someone's lab over that period, so that should give individuals a good understanding of what research should be like.
Obviously, they'll be engaging with other postgraduate researchers and just witnessing what it's like. And maybe they’re hearing people bitching about how horrible research is, or people saying how amazing it is and sharing their successes.
If the student doesn't like research after their master's, at least they've got a master's, which is a higher qualification than the undergraduate degree. So really think about things. And if you do want to do a PhD you should know that fairly soon. That's from personal experience.
Academia or industry?
Industry and academia are quite different entities. The main difference is that, in academia you're going to be focused on something that's very specialised in terms of the laboratory you're in, and the chances are that you will deviate very little from that project over the entire period.
Academia is focused on knowledge, whereas industry is focused on money. In industry it’s about a goal-oriented endeavour. So you could be working on something for say three months, and then a senior management team might decide, ‘Okay, we've spent enough money on exploring this avenue. We need to cut it down and we need to move into other areas’.
That's the broad distinction between the two. But industry does have some research and development areas in there as well, and that might be something more similar to academia, where you're able to explore things in more depth. Essentially, you are part of a much bigger machine in industry, and that means that you have to have a dispassionate approach towards your research.
I am extremely passionate about what I do, and I would find it really hard for the head of the faculty or the head of my school to say: 'Right, you need to change your direction’. Not only would I find that offensive, I would find it really difficult.
But that's the sort of thing that you would have to put up with in industry because it's so task focused, or goal focused that you are given a limited amount of time to prove the project's worth. If it's not worth doing, it will get pulled.
But you can learn a lot of things. With industry, there's a lot of movement within organisations. With academia, there is some movement, but there's some quite hard-trodden paths that everyone has to go through - so doing your PhD, your postdoc, and then going on to becoming a principal investigator.
PhDs are also useful for many other things and they involve many transferable skills. But a broad distinction between industry and academia is how passionate you are about your science, and whether you would find it hard to leave and to switch gears into doing something else.
What habits have helped you?
This goes back to managing staff and interacting with people. Communication, I believe, is the biggest habit to have. I get very excited when I go to conferences. I love being exposed to the science, and I love interacting with people.
I find that that's the best way in which collaborations are made, and the best ways in which your science can advance as well. I'm quite a chatty person, so I have acquired this habit of communicating a lot with others and whipping up a lot of interest and excitement over potential collaborations.
Are there any mentors or people that you've met throughout your career who have had a lasting impact on you?
I've had a PhD supervisor, Sue Cottrell, and two postdoc supervisors, Ann Ager and Anne Ridley. There was Dorian Haskard, who was my Wellcome Trust sponsor - he provided me with space within his department. Then there was Ajay Shah, who is now the interim executive dean, but he was my head of school. All of these people have played a big part in my life.
I love the fact that I was basically reared into science by women. They have such an important role to play and insights - just as men do. I can't think of any exact individual aspects of them that influenced me, but they all did have a big influence in the way that I manage my people and do my science. They were extremely nurturing people.
In terms of the people who everyone else might know, who I really look up to, they are Emmanuelle Charpentier and Christina [sic] Doudna. You probably know these two women as the recipients of the Nobel Prize for chemistry last year.
The reason why I really admire these women is because they were just doing science for the hell of it. They were interested in understanding the immunity that bacteria have - an immune defence that bacteria have against viruses. They realised that they had this machinery that can chew up viral genomes and prevent the virus from replicating in these bugs.
But through understanding that, they realised that they could harness the potential of what's now commonly called ‘genome editing’. Back in 2012, they published a paper describing this in the Journal of Science. Roll forward eight years and they get the Nobel Prize.
This is an amazing feat and to me, this is a shining example of why you should do science if you're interested in it, because ultimately, something super cool will come out of it. Everything in life is interconnected, so it doesn't matter how boring someone thinks your molecule is. It's connected to everything.
There's very few things that are useless in life. We talk about tonsils and the appendix, but in terms of biology, everything has a purpose. It hasn't been weeded out through evolution, so there's an importance for it in life science.
If you weren't able to have your current career, what job would you do instead?
I really enjoy interacting with people and love being creative, so I would probably need to put those two things together. I know how hard it must be to run a business, and I wouldn't want to run one because it means you have to think about making money. Money is the main driver, and money has never been a big driver for me.
But if I could own a café, and exchange recipes with someone, where I'm being creative, and if that café was nestled in a really cool community, then I could have some super interesting conversations with people and be creative. But it's hard to see what my other job would be.
Do you have a healthy work-life balance?
I would say I don't, and part of the reason is because I don't have a partner. I don't have a family, which means that my time is not dedicated to raising children. I don't feel that I have to structure my life towards making sure that my family is okay and that they're supported financially and emotionally.
So that means that I can really dedicate a lot of my time and effort to science, and reading around science and nurturing my interests.
But I do have some amazing friends. Rufus and Javier are my best friends. We met when we were 11 years old at secondary school and we're still good friends today. We go on holidays together. Whilst their full-time jobs aren't really what they are passionate about, they have amazing creative hobbies - namely film and photography - and they get me involved.
We make short films together. They use me sometimes in photo shoots. So it’s great to have amazing friends like that, who just pull you out of the world of science and throw you into the realms of art and photography.
Then there's my dad who, in a way, is a responsibility. I'm very lucky to have a father who's still alive. He will be 96 in August. He's self-sufficient. My brother did an amazing job in looking after him over the lockdown period. I cycle to see him on the weekends.
I love cycling. I cycle to Brighton or Whitstable, or if I'm in London I'll be doing loops around, from Brixton where I live, up to Hampstead and then back down to Crystal Palace.
During lockdown I made a lockdown garden. I've got a tiny yard, but I've brought in ten planters, 2700 litres of soil and over 60 species of plants. I've had this back yard for about ten years, and I’d done nothing to it, but you realise the importance of the space that you have to exploit when you're locked in your house.
With my work-life balance it is very hard to steer away from science, but some of these things that I've mentioned are what brings me out of that science cloud and into some form of reality.
What advice would you offer to your younger self?
I was interested in biology from a very young age. I was born in Ladbroke Grove and grew up in Shepherd's Bush. My parents come from very rural parts of former Yugoslavia and, as a kid, I would go and visit their farms and just be absolutely amazed by how people lived there.
Some of them didn't have running water. They were all self-sufficient, living off the land, and it was an amazing exposure for me. I think my love for biology came through those trips.
I would encourage my younger self to make more of an effort to go to the US. The United States is where you have the most flexibility and diversity in science, and possibilities. We are an excellent country for scientific research, don't get me wrong.
We're leading in Europe and we're probably second in the world, but to have a postdoctoral experience in the USA would have been just amazing. So I probably would have kicked myself up the butt a bit more and forced myself to go out there.
What five things would you take to a desert island?
You're not going to like this answer. I would take a speedboat and four tanks of fuel with the hope that the fourth tank will get me to dry land, because someone needs to run the lab!
Medspire podcasts are produced by Dr Sanketh Rampes and Dr Anvarjon Mukhammadaminov, both full-time junior doctors. They aim to inspire the next generation of doctors and scientists by exploring the career journeys of leading clinicians and researchers.