FOCIS Centers of Excellence
Duke-NUS Singapore
About Salvatore Albani, MD, PhD
Career path
1. How did you first get involved in immunology?
I’m an MD, PhD. But my first inspiration was to be an MD. I loved the idea of the daily routine and the physical and psychological contact with patients. I was in my fourth year in the medical school, and there was this child I saw during my rotation in pediatrics. His name was Antonio and he had juvenile arthritis. He was bedridden. All his joints were swollen and painful and he could not move. But his eyes were bright. This was many, many years ago. The treatment was primitive, and, in that case, we were giving shots of a drug called prednisone. So we gave him a shot. The next day we were doing the rounds and all of a sudden, this little guy comes limping, running and hugs me and that was it. That was when I decided to devote my life to immunology.
2. Tell us about the research you’re most proud of.
I think that the fame and fortune are a byproduct of trying to be useful. When they make us take the Hippocratic Oath, I believe in it; essentially it is being useful to people. It makes me proud, regardless of who performs the research.
3. What is the most important trait a researcher should possess and why?
Compassion is why we are doing it. Then I would say creativity and resilience. This is one of the most schizophrenic jobs in the world and if you are not schizophrenic in a positive way, you cannot be good. You need to believe in what you do and if all your work crashes one day and rises to the heavens the next day because of the data, you need to be resilient. You also need to be humble.
4. What is the biggest lesson you’ve learned?
That I can be wrong, as long as you’re right again, of course.
5. What advice would you give to young researchers just starting out in the field?
Translational immunology is an interface where technology is harnessed and used to address some medical needs. So this is a very special breed, which we try to develop with FOCIS and other initiatives. You need to have resilience and not allow your dreams to be stifled by bean-counters and the reality. Because at the end of the day, if you don’t believe in what you’re doing, why are you doing it? Then it’s just a nine to five job. So be resilient, keep dreaming, don’t let the reality squash your dream.
6. Describe your average workday.
This specific period is not totally representative. Because of the Coronavirus, we are working with three teams and these three that I direct, we only have 20% of the workforce available and I haven’t been doing any wet lab work, so I stay home. But on a regular day, most of my work is theoretical and international so I get up at 7:15 am or 7:30 am. The first thing I do is to breathe before I go on the computer to ground myself with the reality and be ready. Then the gates of Hell are opened because I get emails from Europe and the US and that’s often more than a hundred. Then I set up my work program with priorities. I get reports on the individual projects from the team leaders. I have to organize the work. But the most fun part for me is the science, that’s the real fun part. My office has a couch and we sit there – there’s no psychotherapy, just science. You have people coming in and out and in and out. Someone knocks on the door or calls on the phone or you get an email and I wonder what’s going on. There’s a constant in and out of people. I believe I put items in four boxes: the urgent and the important, the important and not urgent, the not urgent and important and the non-urgent and the not important at all. But that’s the way I work. I love talking to people.
7. Who do you most admire and why?
I admire people who can do things that I cannot do. It’s a complete sacrifice of whatever they have, which I’m not sure that I can do. I can set priorities and work very, very hard. I admire people who can use their lives for something. There have been a lot of doctors who are dying in this pandemic because they did not have the proper protective equipment. You are working around the virus. Those are people who have given their lives and I admire them.
Work with FOCIS and FCE's
8. Switching gears, how did you first get involved with FOCIS?
I’m a friend of David Hafler and Maria Grazia Roncarolo and I was involved from the beginning. What I do is very much along the lines of what they do, which is advanced translational immunology, understanding the immune mechanisms of disease and using the knowledge to improve therapy. I’m a total fan of FOCIS and in fact, I’m very happy about the possibility of doing something tangible.
9. How has FOCIS changed your world?
FOCIS has certainly given me inspiration for the things we do. It gives you an outlet, it provides a stage. Things that are really good in life are always manifested in two ways: we give and we take and FOCIS is part of that.
10. If your colleague asked you why they should join FOCIS, what would you tell them?
It broadens your perspective. I’ve been involved in education for decades. I’m always concerned about teaching young people to think in boxes, which means they’re prime candidates to be replaced by artificial intelligence, particularly physicians. What FOCIS can do is break the boxes and help you think in a different way, to connect molecular mechanisms with a person who is in bad pain. And that, I think, is the value of FOCIS – to bring the lofty ideas down to the ground level so they become useful.
11. Tell us about the research you’re doing.
My interest is to understand immune-mediated mechanisms of disease and then use the knowledge to take care of the way we approach these diseases, either to improve therapies or create new ones. I’m a rheumatologist, so my main focus has been autoimmunity. Over time, I’m very proud to say that I’ve made a lot of mistakes because I’ve learned from them. And I’m also very proud to say that I could go all the way from a completely abstract idea to advance the clinical trial for a second-class drug which is a vaccine for a trial. I developed other technologies and one that I’m particularly proud of was developed here in Singapore. It’s a completely innovative way of looking at the immune system. We created a very large data set using a high dimensionality approach – so it’s the equivalent of taking a high-resolution MRI from many, many people starting from fetus to 90-plus years old. The information is not from an MRI, of course, it’s the immune system. So essentially, this is the data set which represents the normal. We have a normal picture of a high-dimensional, very high-resolution image of the normal immune system. And we developed the artificial intelligence tools to interrogate, mine, in any way you want, the immune system. You can also build the architecture of the immune system, depending on age and the group or patient. At this point, you have a tool which enables you to consider diseases as aberrations of the normal immune system. If you study a certain disease the same way you study the normal, then you can match and immediately pick up on what is different in the disease and zero in on the mechanism or predict the outcome of the therapy. You can say this guy’s going to do well, this guy’s not. We’re doing this for COVID. What we’re working on specifically – trying to understand how the virus changes the architecture of the immune system and based on these changes, we try to understand why some people do well and some others don’t. And in those that are convalescing, who are healed, there is something in their response that we can dissect that will lead eventually to a vaccine. You can understand in broad terms how powerful this technology is. You can predict what will happen if you take a certain drug out of a patient and not for another one, while both are doing well, etc. This is a new technology and there’s a very broad potential for the future of medicine, not just for us, but in collaboration with others. And then we are taking a different tack on cellular therapy, the CAR T-cells. We are manipulating the cells in a way so they can regulate when there is too much information and this is a very, very exciting approach because it may overcome the need to do it for each individual patient. We can have a tool that will work for everybody. There’s a very vibrant environment here in Singapore with many students, young people who are growing, it’s very nice, very nested within the hospital and medical system.
12. What is your vision/dream goal of your FCE?
To be useful and then measure being useful in numbers – how many people you have trained, what are they doing, have they been successful, how many patients’ lives have you touched, how many patents you have written, how much money you have raised. The reality is the impact on the very society which is supporting you, because we cannot forget and should not forget, that this research is being funded by people, by taxpayers. And I treat that money like my own. We are responsible for it. I consider money from the people as an investment. I also try to attract investments from private sectors. It’s necessary that we get away from the ivory tower of research and academics and deal with the reality, the people and the needs and work together with all the components of society in order to be useful. I was in San Diego and was very happy for many years. But seven years ago, I went to Singapore because I was dealing with a blank slate here, because I could build something that was truly translational. This is different than in the US and the EU where the systems are very fragmented. And here the possibility of going through the entire gradient of translational research inspires you and then you can use the resources and technology to address that.
13. What are your biggest challenges?
The real challenge is to break the mold if you want to do something really new, let’s use the term, first in class, and do something nobody else has done. If you want to develop a completely innovative new idea, the hurdles are immense. There is an establishment consisting of a very crystalized standard of writing procedures, which applies to each of the sectors that you need to go through. You have the regulatory, the industry, etc. You need to find the money to develop the idea and maybe you can do the first steps through grants. Then you need to raise the rest of the money to really bring it to the patient. You have regulatory hurdles, like with the FDA, etc. They have very standardized procedures. For instance, I develop a vaccine which works in only humans, but they want me to do it in animals. And I tell them it doesn’t work in animals. I can’t. I can do something similar, just to show the concept but I cannot use the same substance to prove that it works in animals because it was designed for humans. Then when you want to go to industry, you need to raise many millions. It costs one billion dollars to develop a new drug from zero – and that’s within 15-20 years. To get to the money, you need to be innovative and yet fit yourself into the mold and that’s the biggest challenge. It’s contrasting the new thing, the revolutionary thing, within the context of the very conservative standard of every procedure.
14. Why did you apply to be an FCE?
I think FOCIS is very, very important. I would use the word essential for the success of making immunology useful to people. And there isn’t much or anything actually in Asia. I think we are the first or among the first. I talked to Maria Grazia and others regarding the opportunity and the challenge at the same time. Where I live is a very special place. Singapore is the second or third largest income in the world. It’s a high-tech, deep-tech hub. From my window, I can see Indonesia or if I cross the bridge, I can go to Malaysia. It’s a completely different world. And there are hundreds of millions of people who can benefit from what we do. And the way we do it is through knowledge. We cannot do anything alone. No matter how great you are, you can’t do it alone. But if you create an ecosystem which thrives, then you can be of help to society and that’s why I proposed that the Center of Excellence be housed here. So, Singapore is a high-tech hub and a pivot around the largest untapped audience in the world. This is a major opportunity.
15. Talk about your collaborative efforts in Dubai, Japan, China and Oceania.
Our network of collaborations is completely international. It even includes Africa. But how do you make an impact regionally, where regionally is a very, very large area. So, of course, you have bilateral cooperation, which is great, but relies on knowing someone in Kyoto or in Paris or wherever. And then there are unmet needs that you can address in a different way. I’ll give you two examples. Many years ago, I started a non-profit foundation with several friends, David Hafler and Maria Grazia Roncarolo, among them. It’s called the Eureka Institute for Translational Medicine. You can find the website at https://eurekainstitute.org/. It was formed to share with international people the mistakes, which I, Maria Grazia, David and others made, regarding addressing unmet medical needs through technology. I transplanted the Eureka Institute here in Asia and we offer a lot of things ranging from one-week courses to a Master’s in International Medicine as well as other initiatives, including mentoring and research opportunities throughout the area. It follows the path of translational medicine, not just immunology, though immunology is a very important part of it. The second initiative is called UCAN-A, which stands for Understanding Childhood (Chronic) Ailments, Networks for Asia. It’s a way to take children who have nothing, who have serious diseases, immune-mediated, and give them the opportunity to be treated and also the opportunity to participate in research. There’s a hub in Singapore and Dubai and we hope to expand the program soon in Japan, Australia and Chongqing in China. The idea is to start with some selective immune diseases. We chose to study rheumatic fever for its relevance in the area and some other immunologic diseases. Children are diagnosed and treated by standardized treatment. We collect homogeneous data and the samples from the entire network. This means we can look at the data and look at the samples and understand what’s going on in terms of global health, all molecular immunology. This is another initiative which we have launched in the area of immunology for children. If it works, we will have the largest network for translational research (and clinical trials).
16.What’s the status of your therapeutic approach to rheumatoid arthritis?
This project is essentially almost my entire professional life. This is a first in class tolerogenic vaccine for Rheumatoid Arthritis. It is in advanced clinical development, as we have completed Phases I and IIb, we are ready for phase 2B, which means we have proven the necessity, we have proven we have a very good indication of clinical efficacy and now we need one more phase before we take it to big pharma. And I’m very excited about the opportunity of shifting the work in collaboration between the Institute and Ardion, a Singapore start up. So we are building the necessary plan and finding the resources to complete the next big step in development. I am confident that we will be able to successfully complete the journey from idea to innovative product.
17. What are novel targets for therapy in patients with autoimmune diseases?
The technology is called EPIC (Extended Poly-dimensional Immunome Chracterization), which was published in Nature Biotechnology in June. It’s the AI powered, the high-dimensionality tool, which I was describing earlier. And this is the one that builds the architecture of the immunome and then can distill what disease does in terms of aberration towards the healthy architecture. This is a very important tool to define new targets for therapy because as we find the mechanisms which are specific to the pathogenesis of the disease, then we can zero in on the molecular target. I want to underscore that nobody has the golden nugget, the solution for everything by themselves. Science is a collaborative work and so nothing is going to happen if we’re not connected worldwide and this effort can be a crucial conduit for this.
18. CAR Treg
CAR Treg is a cellular therapy where you take the T-cells out of the patient and you engineer them, then you put them back into the patient. The target is usually Cancer to improve the immune response. In controlling intensity of immune responses, like with lighting in a room, you can replace on-off switches with a dimmer and you can modulate the intensity of the lighting using the dimmer. Similarly, with Immune Responses if you need more, you can turn up the dimmer and if you need less, you can turn it down. That’s immunotherapy both ways. And what we do with CAR Tregs and also with the vaccine for Rheumatoid Arthritis, is to turn the dimmer down, to reduce the intensity of the immune response by exploiting living cells (our dimmer approach) rather than blocking individual molecules (the switch approach).
19. Talk about the educational programs you’ve conducted and how you’re working to promote, become involved with any FOCIS-related initiatives.
Yes, that was one of the top things which I wanted to do together with FOCIS. For July of this year, we had two very exciting initiatives planned. Unfortunately, we have to talk about them in the past tense since we had to postpone. The first two days of the event were an advanced class in translational immunology to be held here in Singapore, open to anybody who wanted to attend, limited to 100 participants from anywhere in the world where the principles of translational immunology would be taught. The audience could be quite broad, from physicians who wanted to brush up on their immunology to students, etc. and followed by several other initiatives FOCIS has worldwide. Last year, we had a similar course in India. Right after that, I was planning a meeting in translational immunotherapy which was supposed to be very ambitious, a modern, up to date approach on how we treat patients using immunology. This was FOCIS-sponsored, but I thought it was wise to postpone it because of the current situation. And then I have the Eureka Institute initiative, which I’ve been very involved with as well.
Personal
20. What motivates you to work hard?
Remembering Antonio and the millions of Antonios is the world. I’m a physician with a very limited clinical activity because I do my research. My motivation is to do the inventing side of things which touches many, many lives. That’s what motivates me. But the beauty of it – and I think I’m very privileged – is because the work I do is not a job, it’s a mission. It’s a mission where strict hours aren’t involved, so if I have a great idea in the shower or somewhere else, it motivates me in the hope that it will eventually be useful.
21. What is your favorite time management tool?
I have a black book and I use a fountain pen. Every day when I sit down at my computer, I write down the list of my priorities and I like scratching them all off by the end of the day and that’s not always possible. My mind and heart are how I define my time. I tried the software programs, but they try to put your mind into pre-set boxes and I don’t think that works for me.
22. Do you have a favorite vacation spot?
I’m very, very far away from my hometown, which is Siracusa, Italy. But my passion is traveling, so I really enjoy going around everywhere, eating what everyone else eats and doing what they do. I like diving and sailing. The Maldives are very close to Singapore, that’s a great place. Indonesia is great. Traveling in general makes you a better person.
23. What is your favorite beverage or drink?
Sicilian wine.
24. Describe your hobbies. What do you do when you’re not working?
Traveling, definitely. I’m a competitive rower too, so definitely rowing. I love to compete.