From Owo in Ondo to Germany, obtaining a PhD in the field of Cancer Biology, despite having studied Agriculture with zero experience in the field of Cancer Biology, to working in the second biggest pharmaceutical company in Germany and the biggest privately-owned pharmaceutical company in the world, NIYI OLAREWAJU is indeed a success story. In this interview with Associate Editor, KEMI AJUMOBI, he opens up on his journey including the travails and triumphs. Excerpt.
Olaniyi Olarewaju works as a researcher in Germany’s second-largest pharmaceutical company, Boehringer Ingelheim Pharma. His research work primarily focuses on optimising and improving adeno-associated virus (AAV) vector platform as a gene therapy tool for treating genetic diseases. He hails from Owo in Ondo State and earned a Bachelor of Technology degree in Animal Production and Health (APH) from the Federal University of Technology Akure (FUTA) in 2011. He proceeded to the University of Bremen, Germany and later Christian-Albrechts-University in Kiel, Germany where he studied M.Sc in Agricultural Genomics. During his Master thesis, Olarewaju studied oxidative stress tolerance in entomopathogenic nematodes used in biological control of crop pests. He became interested in the connection between oxidative stress and the molecular processes involved in the development of cancer, which spurred him to pursue his PhD in the field of cancer biology. Defying all odds, Olarewaju earned his PhD from the Hannover Medical School in Germany where he studied the roles of small non-coding RNAs in hepatocellular carcinoma (liver cancer). In the course of his PhD work, Olarewaju learnt about the application of AAVs as a vehicle for delivering gene therapy for treating genetic diseases. He successfully used AAV to deliver an antagonist of an oncogenic microRNA which promotes liver cancer survival and concurrently prevent the liver cancer cells from undergoing programmed cell death.
From Ondo to Germany, it has indeed been a journey filled with various experiences. Tell us about it.
First, thank you very much for this opportunity. I was born and raised in the ancient town of Owo, in Ondo State where I started my primary school education at St Michaels’ Nursery and Primary School, Ijebu Owo. I proceeded to the Federal Government College, Ido-ani for my secondary education which I later completed at Owo High School, Owo. In 2006, I gained admission to the prestigious Federal University of Technology, Akure (FUTA) to study Animal Production and Health. I graduated in 2011 and undertook the compulsory one-year NYSC programme which I completed in 2012 in Ibadan, Oyo State. Well, traveling to Germany was not actually my plan. I remember vividly upon returning to Ondo state after my NYSC, my goals back then were to become a livestock farmer and pursue my passion for politics. I had prepared my farm business proposal and my parents were supportive and had gathered a decent amount of money for me to start the farm.
However, I approached one of my uncles for additional support for my proposed business, but instead of supporting, he encouraged me to pursue a M.Sc. degree abroad, experience new culture and see first-hand how developed countries work. That was really the point where I suspended my business plan and started looking for M.Sc. opportunities abroad. Luckily at that point, I also reestablished contact with a friend of mine from FUTA who was studying for his M.Sc. degree in Germany. We had a chat on Facebook, and he was kind enough to convince me to opt for Germany. Based on his experience, Germany is an amazing place with a lot of opportunities and studies here is basically tuition free. So, I jumped at the opportunity and here we are 10 years after.
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You successfully used AAV to deliver an antagonist of an oncogenic microRNA which promotes liver cancer survival and concurrently prevents the liver cancer cells from undergoing programmed cell death. Tell us more about spearheading this.
Yes, in my PhD work, I studied some of the complex processes involving microRNAs that drives hepatocarcinogenesis (liver cancer development). I particularly focused on the roles played by microRNAs in these processes, knowing fully well, that if we can identify some of the microRNAs involved in these processes, we can target these microRNAs and explore them as potential therapeutic targets. In simpler terms, these microRNAs are small non-coding RNAs usually about 18–25 nucleotides. They have the ability to bind a regulatory region at the end of our messenger RNA (mRNA) which prevents the processing of these mRNA to generate matured mRNA from which our proteins are derived or translated. In cancer, we know that the mRNA encoding for some tumour suppressor proteins like TP53 are targeted and destroyed by these microRNAs leading to the loss of these key proteins that guard and prevent our cells from undergoing uncontrolled proliferation. On the other hand, we have proteins in our cells like c-Myc and K-Ras proteins that promote rapid cell proliferation and cancer development. We know some microRNAs help to control the levels of these tumour-promoting proteins by targeting and reducing their mRNA levels. Unfortunately, in some cancers, we see that these guardian microRNAs are lost leading to the uncontrolled expression of these tumour-promoting proteins. I am profoundly proud of what I accomplished with my PhD thesis, the data is robust, and I identified a unique and novel mRNA targeted by one of the microRNAs I studied. We are currently putting finishing touches to the manuscript where these findings will be reported.
This treatment led to a significant reduction in liver cancer progression in multiple mouse cancer models tested, has it been used on humans?
No, not yet. There are tightly regulated processes for that, and it is a very long and tedious journey to experimenting new/potentially new drugs in human. It usually takes 6-8 years of research for a drug to be tested in human. The case of the COVID vaccine was different because everything was accelerated. However, the classical path to testing new therapeutic substances in human starts from target identification and preclinical studies in vitro (living cells cultured in the lab) and in animal models. In my study for example, I have successfully shown in vitro using human liver cancer cells that if I inhibit the microRNA in these cells I cultured in the lab, the cells significantly proliferate less, and they are also susceptible to apoptosis (cell death). Next, I tested this in three different mouse cancer models, and I observed the same result. To go forward, we should then go and test in non-human primates, like monkeys which are closely related to humans to see if we will get the same result. Then, you still have a lot of other steps you must follow. If it works fine in the monkeys, then you must do a lot of optimisations, you have to analyse and define the mechanism of action of the antagonist we are using, you have to think of how to formulate your drug substance, the pharmacokinetics and pharmacodynamics. It is a long path, and it takes massive effort to translate the basic research we do in the laboratories at the universities to the clinic where the patients can then benefit from the therapy. This is also one reason why I decided to continue my research journey in the pharmaceutical industry where the workflow is already optimised for drug development.
How reliable are experiments done on mouse enough to ascertain it is okay to try on humans?
Well, some experimental data from mice are quite translatable to humans, but you mostly have to validate the data in a higher model like non-human primates and even pigs or dogs depending on the disease you are looking at. For example, we know the pig’s heart is very similar to that of human and that is why a lot of preclinical studies for treating heart diseases are done in pigs before trying in non-human primates or directly in humans. Lo and behold, especially in my field of research, I will say that experimental data from mice is largely insufficient to translate to running clinical trials in humans. Nevertheless, you have to start from somewhere and then follow the data.
You joined the lab of one of Germany’s foremost AAV experts and the immediate past president of the European Society of Gene and Cell Therapy (ESGCT), Professor Hildegard Buening as a post-doctoral research scientist, share on the advantages of these opportunities
It was indeed a big opportunity for me, and I am forever grateful to Prof. Büning for that. I used adeno-associated virus (AAV) as a vector delivery tool to deliver the microRNA antagonist to the target cells and tissues in my PhD work and my interest in AAV just grew from there. So, after my PhD, I felt I should learn more about these viruses and how you can engineer them to become more specific for targeting the tissue you are interested in delivering therapy to. For example, it will be desirable to engineer AAVs that after injection into the body, they will go only to the heart to deliver specific therapy to treat a genetic heart disease and not got to the liver or muscles or kidney for example. I was lucky to have been accepted in the lab of one of the world’s foremost experts on AAV gene therapy and AAV engineering.
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Tell us about working on the optimisation of AAV gene therapy for the treatment of haemophilia, genetic disorder. What was the discovery? Is there hope for those who have it?
There is a limit to what I can say on approaches we took in this direction. However, in 2022, AAV gene therapies were approved for treating Haemophilia A and Haemophilia B. To be precise, Roctavian was approved to treat Haemophilia A and Hemgenix for Haemophilia B. For Haemophilia A, AAV was used to deliver a functional copy of the FVIII gene which is defective in people living with Haemophilia A and for Haemophilia B, AAV was used to deliver the correct copy of the FIX gene which is the defective gene in people living with Haemophilia B. However, for Haemophilia A, Roctavian majorly delivers the functional copy of FVIII to the hepatocytes, the primary parenchymal cells of the liver, and these cells will then serve as factories to produce the correct version of FVIII protein. We think this is not optimised enough, because many literatures have now suggested that the hepatocytes are not the main cells naturally producing FVIII in the liver, and forcing the hepatocytes to manufacture this complex and difficult to process FVIII protein can cause problems for the hepatocytes. These hepatocytes might get stressed and even die and this can reduce the efficacy of the treatment in the long run, especially since AAV gene therapy is currently being marketed as one in a life-time treatment. So, we thought it is worth revisiting the approach and then engineering AAVs that can go very specifically to target and deliver its cargo to the right cells which naturally produces FVIII proteins.
Will there ever be a cure for cancer? How close are we?
There are still challenges on the road to achieving total cures for all the different types of cancers that exist. However, there is hope on the horizon. The field has rapidly evolved in the last one decade especially with the type of powerful technologies now available and how different -omics tools and big data are being deployed. Today, we talk of personalised medicine where a patient’s treatment is tailored to his/her disease aetiology, we understand in better details the mutation landscapes that culminate in cancer development. Look at the recent breakthroughs with cancer-immunotherapies where the immune system is retrained to find and kill cancer cells that are quite exceptional at evading immune surveillance. For blood cancers, the field of bone marrow transplant is growing rapidly and breakthroughs in stem cell therapies are completely revolutionising treatment opportunities for patients. These advances are not only around treatments, but big progresses have also been made in understanding the predisposing factors to many of these common cancer types. For example, high alcohol consumption, hepatitis B infection and abuse of drugs like paracetamol causes acute liver injury and in the long run may lead to liver cancer development. These are very big risk factors for liver cancer. We know a persistent infection with human papillomavirus (HPV) is the highest single risk factor for cervical cancer development. So now, vaccination against these type of viruses as well as changes in lifestyle can help with lowering the risk for cancer development in the future. Also, we are in the era of genetic testing, where one can screen to know if one carries mutations in some of the commonly mutated cancer genes and so on. How close are we to finding treatment is one question, how close are these current ground-breaking treatments and screening platforms available to millions of people in Africa is another.
You had your MBA after your PhD, what imformed this decision?
It was at the end of my PhD that I knew I had to do an MBA. I was not sure how fast I would get a postdoc position or a job after my PhD. So, in that time of looking for a job, I thought I could also use that opportunity to enrol for the MBA programme. Fortunately for me, I started a postdoc position three months after, so I had to combine the postdoc with 20-hours a week MBA classes. It was tough, but I survived.
With your continued research on diverse approaches to genetically engineer the capsids of AAV vectors for improved gene delivery, what do you hope for?
I left academia last June to continue my research journey in the pharmaceutical industry. Luckily for me, I got the opportunity to continue work on capsid engineering approaches for the AAV so that we can deliver these vectors to the target cells or tissues in a very specific manner. In the industry, one has more resources and access to a lot of fancy and powerfully equipment. I am able to drive my research activities faster with a lot of support and I am also now opportune to work in a translational research group where the primary goal is to develop AAV gene therapy products for the benefits of the patient, to cure diseases and improve their quality of life. Within the context of my work, I am also developing fancy and potent ways of targeting our AAVs to target tissues. Luckily for me, despite being in the industry, we are still allowed to share many of our approaches and findings with the larger scientific community. So, stay tune for my manuscript on these approaches hopefully by the middle of 2024.
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If your name were to be written in history for what you have done so far, what feat will be recorded that you achieved, especially as an African?
Well, I am my feats, and I am my achievements. My journey in the last 10 years is improbable. Starting from Owo to FUTA and to where I am today, working in the second biggest pharmaceutical company in Germany and the biggest privately-owned pharmaceutical company in the world. Sometimes, I still do not believe this is me and that I can come this far. In FUTA, I studied Animal Production and health and graduated with a second-class lower grade. Getting to Germany, I studied M.Sc. in Agricultural Genomics, earning first-class in three of my four semesters, the last semester being a perfect score which is equivalent to 5.0 in Nigeria. My interest in learning about cancer towards the end of my M.Sc. programme led me to obtaining a PhD in the field of Cancer Biology, despite having studied Agriculture with zero experience in the field of Cancer Biology. Not sure how I managed to get into one of the most competitive PhD programmes in Germany, but I was fortunate to be one of the 18 students accepted into the PhD programme out of over 450 applicants. I set my goals, I work hard and put all my trust in God that He will see me through. Looking back and seeing how far he has brought me and everything the Almighty God helped me achieve, I am simply grateful, and I have no doubt my life itself is my biggest achievement. Yes, I am still a body of work in progress, and I believe my best is yet to come. So, I believe there are greater heights to climb and longer distances to cover.
Despite your challenges, what has kept you going?
My faith in God and my audacious believe that no mountain is too high to climb, so long you put your mind to it, and if you work hard, every dream is possible. Also, every time I remember how my parents toiled to provide me the best they can, I just know I have to make them proud. Sometimes, in my lowest moment, all I need to do is think about them, especially my mother and how far she is ready to deny herself everything because of me and I will quickly realise failure is not an option. Furthermore, I believe in the goodness of the human heart and that if you work hard enough, you will become visible and there will be someone out there who will notice you and will believe in you and be ready to support you and stand with you. At every defining moment in my life in my journey in the last 10 years, I have met someone who encouraged me and believed in me.
What advise do you have for people going through tough times and cannot seem to see light at the end of the tunnel. Using your story, encourage them
First and foremost, tough times do not last. Yes, I went through a lot of difficulty right up till the end of my PhD. Sometimes, I really try to remember how difficult those moments were, but the pains are all gone. Whatever you are going through today, stay focused and try as hard as possible to keep the focus in mind, because the joy that comes with achieving your goals will override the remnants of the memory of your pain and hardship. Do not give up, find people you can share your thoughts with, people who can guide you, genuine, reasonable, and forwarding looking people. Be very selective with the quality of people you allow around you, that can prove very vital in your most difficult moments.
Despite some negative perception of Africans on the international scene, people like you are giving the country a good name, how does this make you feel and how important is it for the negative narrative to change?
Well, it is worrisome, especially how we are stereotyped even without getting to know who we are. In my earlier years in Germany, I experienced a bit of these stereotyping, but I quickly established myself and defined who I interact with or where I go to, just to avoid some embarrassment. I established my own narrative and to some extent control what you perceived of me. Luckily for me also, my life revolves around highly educated people who are respectful, smart, well-travelled, and exposed, this, to a large extent insulates me from the normal hustle and bustle on the street. I believe, we all have roles to play as individuals, to strive to always be on our best behaviours. We have roles to play as Africans to control our narratives and the message we tell the outside world. It is when we do that, that the international community will also adopt our narratives and how we want to be perceived.
You are doing well in Germany because their system works. What candid advice would you want to give the Nigerian government?
My advice to the Nigerian government is very simple. A working society is possible if we have the will and desire to make it possible. It is as simple as that, and I don’t believe people in government in Nigeria are not aware of that.
