The Humans of the Wyss (HOW) series features members of the Wyss community discussing their work, the influences that shape them as professionals, and their collaborations at the Wyss Institute and beyond.
Harkamal (Hark) Jhajj is always climbing physical and metaphorical mountains. In his spare time, he loves doing physical activities and exploring nature by hiking and visiting national parks. In the lab, he breaks down large problems into smaller steps, ascending hills until he reaches the top of the mountain and finds a solution. Right now, he’s leading the RESTART project, and the “summit” is developing a cell therapy to treat bone fractures by reprogramming aged regulatory immune cells into their youthful counterparts. Learn more about Hark and his work in this month’s Humans of the Wyss.
What are you working on?
I’m leading the RESTART project, a second-year Validation Project aimed at identifying transcriptional rejuvenation factors that can reprogram aged regulatory T cells (Tregs) into their youthful, more functional counterparts. Tregs are an exciting subset of T cells, a type of white blood cell, that maintain immune tolerance, modulating your immune function.
We’re focusing on a cell therapy to treat bone fractures. Our idea is to incorporate the therapy into biomaterials, such as a hydrogel, and inject them via a minimally invasive procedure.
What real-world problem does this solve?
Worldwide, about 5.5 million people fracture their bones every year. Of those, 10-15% undergo delayed healing or non-union, meaning the bone does not join back together. This is due to excessive inflammation, which can lead to fibrosis and tissue scarring. It is especially prevalent in people over 50 years old, especially women after menopause due to lower estrogen levels. One in two women will experience a bone fracture over the age of 50. These fractures render people unable to move around, and that leads to complications and other diseases.
Current treatments focus on mechanical repair through bone grafting and growth factors, but our bones are not in a vacuum. When you look at the whole picture, including what’s happening around the bone, you see that often, patients who don’t respond have excessive inflammation at the site of their injury, which leads to scarring and non-healing. Our Treg therapy serves the dual purpose of lowering inflammation and secreting cytokines to promote bone repair.
What inspired you to get into this field?
I studied chemistry as an undergraduate. I enjoyed it, but I didn’t like being in the lab because I didn’t feel what I was doing was making tangible progress towards improving human health. During that time, I completed a three-month summer internship at the University of Texas focused on biology. That motivated me to shift my focus. After I graduated, I worked in molecular imaging at Massachusetts General Hospital, where our research focused on vascular disease and the innate immune response. We explored whether you can image inflammation and, once you image it, use therapeutics to treat it. My experience there motivated me to pursue a Ph.D. in bioengineering at the University of Michigan. There, I focused more on understanding the adaptive immune response using protein engineering methods.
What excites you most about your work?
Seeing how what I am doing in the lab can have a direct impact is most exciting. We’re focusing on a problem that impacts people’s day-to-day lives. Scientifically, it’s exciting to combine different disciplines; for example, we’re combining wet lab experiments with computational approaches, supported in part by the Wyss Translational AI Catalyst, and can choose the best tools for the question we are trying to answer. That flexibility and collaboration are really special.
I also love mentoring young scientists and trying to impart my knowledge to them. I enjoy feeling like I am giving back in one way or another, especially as I see how much they’ve accomplished at a young age.
What are some of the challenges that you face?
Science is hard. You think something will take you two months, and it takes six. Experiments are difficult. And we’re working on the challenging problem of reprogramming Tregs to their healthier counterparts. This is tough because it’s more nuanced than just making sure that they’re always active. We want more fine-tuned control. With each large problem, there are smaller roadblocks you need to overcome to reach the end. Luckily, I’ve always liked taking a big problem and breaking it up into smaller chunks to solve along the way. It might seem daunting in the long term, but it’s exciting that you can go up these small hills and eventually reach the top of a huge mountain without even realizing it.
I’ve always liked taking a big problem and breaking it up into smaller chunks to solve along the way.
Why did you want to work at the Wyss?
I like the fact that the Wyss focuses on high-risk, high-reward problems. I also like that it feels like a bridge between academia and industry. COVID-19 taught us that if you really want to develop medicines to help people, you need that connection between the two. I was attracted to the idea of using synthetic biology to address challenging problems.
Also, being in Boston, you’re surrounded by the best scientists in the world. When I was at MGH, I would ride the elevator with Jack Szostak, a Nobel Laureate in Physiology or Medicine. That doesn’t happen just anywhere. Now, being able to work with George Church, who is such a legend, is something I try not to take for granted. The human brain gets used to it, but I think that when I look back on it, I’ll be really inspired by the fact that I had this opportunity.
What is so unique about the Wyss? How has that impacted your work?
The Wyss is a really special place where collaboration is made easy. In other labs, you’re part of an individual department. You can theoretically collaborate, but attempts often fall apart because either one party is more interested than the other, or one is not as incentivized to work as hard as the other. Here, it’s more open. If there’s a scientist in another lab working on the same problem, I don’t need to jump through hoops and go through the PI to see if I can talk to them. I just reach out directly, and that’s made my work more collaborative.
We’re also given the freedom to pursue innovative ideas. You’re not being forced to do things in a particular way. Also, if you do have a good idea, you can apply for a small amount of internal seed funding through the Director’s Fund. If you’re getting promising results, you can apply for a Validation Project. These kinds of mechanisms don’t really exist outside of our ecosystem. We have the luxury of being paid to think about problems and find solutions.
How do you collaborate with and/or receive support from teams across the Wyss Institute?
The clearest example is that our Validation Project is in collaboration with Georg Duda, who’s an Associate Faculty member. His lab specializes in the interaction between bones and muscles, and in the biomechanical influences and their impacts on the intact and injured musculoskeletal system. Our lab specializes in synthetic biology and cell therapies. We’re good at finding problems and identifying what cocktail of changes to a cell would address the issue. They had convincing data showing that T cells could be helpful for bone fractures, so we got together to write the project proposal, and it’s been a fruitful collaboration.
Beyond that, having Sam Inverso from the Business Development Team‘s support is vital. If I have questions about the business side of something happening in the lab or the development of our therapeutics, he can help. If I have questions about patents and protecting our innovation, I can contact Jay Culverwell, our Senior Director of Intellectual Property, for advice and strategy. Coming from other labs, it’s mind-blowing to have such easy access to that kind of resource. Within the Church lab, I also have support from members of the Advanced Technology Team, like Jenny Tam and Alex Plesa. Science cannot be done by one person. It can take many decades to solve a problem, but we can accelerate progress by having the right people work on it together.
Science cannot be done by one person. It can take many decades to solve a problem, but we can accelerate progress by having the right people work on it together.
How have your previous work and personal experiences shaped your approach to your work today?
I’ve always had an interest in translational medicine. Throughout my experiences, I’ve learned that the immune system is important to every disease, whether it’s overactive or underactive. So, modulating the immune system or finding a way to restore it to homeostasis would be incredibly valuable. That idea is shaping my work today.
What do you like to do outside of work?
I really like doing physical activities. That could be going to the gym, hiking, or visiting national parks. I think some western states are severely underrated, like Montana and Utah. For my favorite national parks, Glacier National Park was truly out of this world. Yellowstone is like Jurassic Park. It’s gorgeous, and there are elk walking around everywhere. And then I think photos cannot do the Grand Canyon justice. Your eyes cannot believe there are these huge, inverted mountains. It’s mind-blowing. At the end of the day, we’re animals, and we like to be in nature. Life is more than work, so just go outside and take a walk.
1/3 Hark enjoys spending time outside, especially hiking and visiting national parks. Credit: Harkamal (Hark) Jhajj 
2/3 Hark poses at his favorite U.S. National Park: Glacier National Park. Credit: Harkamal (Hark) Jhajj 
3/3 Hark captured one of the beautiful turquoise lakes at Glacier National Park. Credit: Harkamal (Hark) Jhajj
What’s something unique about you that someone wouldn’t know from your resume?
I actually live in New Hampshire, and I love it there. I’m an hour away from the beach, the mountains, and work. When I worked at MGH, I lived in Somerville, MA, and I didn’t like the constant noise and constant people. Cities are more stressful for me. Living further out, I feel like I can go on a vacation at the end of every day and come back to the Wyss refreshed and ready to work. Some people might not like the commute, but I turn on a podcast and the time flies by.
If you had to choose an entirely different career path, what would it be?
When I’m not doing science, I’m looking at how the stock market is doing. I look up to the famous investor, Warren Buffett. His approach is to understand businesses and what you’re buying, rather than just purchasing whatever stock seems to be going up. During COVID, when I was home for three or four months, I started learning about how to analyze businesses and what makes a good business. I’ve developed a fascination with understanding how the bond market and everyday activities can affect the stock market. So, I think if I wasn’t doing science, I’d do something related to finance and understanding business. Maybe I’d be an analyst at JP Morgan or a biotech analyst.
What does it feel like to be working on cutting-edge technology that has the potential to have a real and significant impact on people’s lives and society?
Knowing that if we discover something important, we can take it directly to patients and have a positive impact on their lives is humbling and empowering. That’s why I like translational science so much, and why I feel lucky to be at the Wyss where I have the support to make this happen.
Knowing that if we discover something important, we can take it directly to patients and have a positive impact on their lives is humbling and empowering. That’s why I feel lucky to be at the Wyss where I have the support to make this happen.
It’s also why I am passionate about working on the immune system. I’m not limited to a single organ or cell. If we can adjust Tregs, we can address so many issues. If you have an autoimmune disease and your immune system is running rampant, we can push it down. If you have cancer and your immune function is down, we can push it up. Applications are everywhere, so it’s exciting to see the scale of impact we can have.