Meet a Whitehead Postdoc: Jaspreet Sandhu

Jaspreet Sandhu is a postdoc in Whitehead Institute Member Jonathan Weissman’s lab studying how the genetics of individual cells determine their behaviors within the liver. He is also a gastroenterologist at Massachusetts General Hospital. We sat down with Jaspreet to learn more about him and his experiences in and out of the lab.

What is your current research focus?

As a physician, I was trained to assess patients’ health by measuring how their organs are functioning. I became interested in trying to understand how our organs fundamentally work. To do that, I use technologies that enable us to look at the individual cells within organs, and as a hepatologist and gastroenterologist, I’m particularly interested in looking at cells within the human liver. Broadly speaking, I'm trying to understand the genetics of individual cells within the liver, and how those genetics feed into how the liver functions.

Historically, the challenge of studying how cells function in organs has been that we often have to take the cells out of the organ. The problem is that, especially for cells in the liver, when you remove the cells from their native context they start to look and act less like liver cells. There is also spatial organization within the liver, so cells can assume different jobs depending on where in the liver they are. All of that is lost when you take the cells out of the liver, so the key thing that I've been doing has been to try to best capture the cells within the liver. I essentially freeze the cells in their native state, and then I do single cell analyses. I’m also looking at the liver in different conditions, to understand how contexts like fasting and diet affect its cells. I’m particularly interested in questions related to fatty liver disease and when and how sugar is made within the liver.

How do you divide your time as both a physician and a researcher?

I have a clinic where I see patients one half day of the week and do procedures on another half day. I also spend a few weeks a year managing consults in hospitalized patients. The rest of the week I'm in the laboratory. I spend more than 80% of my time in the laboratory, but I still take care of my patients throughout the week.

How does your perspective as a scientist affect your work in the clinic?

I talk to my patients about research a lot, to the point where I even show them the latest literature on certain topics. For some patients for whom treatment options are limited, I use it as a way to give them hope about the future. I try to express to them that there are a lot of really talented, hardworking individuals working on what they have. I show them where the biology is now, and my expectation of how that will impact their disease in five to twenty years. I think a lot of patients appreciate that, because it can be very frustrating to hear that we have nothing for them currently. It helps to hear that there is hard work going into something that could impact them in the future.

What did you want to be as a kid?

I loved my pediatrician, so when I was a little kid if they asked me, I would say I wanted to be a doctor. Then I moved away from that and it wasn’t until much later that I returned to that career path. It’s funny, a lot of folks who knew me when I was a little kid weren't surprised when I ended up choosing to be a physician, even though for a long time I did not see myself heading in that direction.

When did you return to your interest in medicine?

It’s a long story. I was a very poor student in high school and initially wasn't particularly interested in going to college. I was actually such a poor student that there was a threat that I would have to do an extra year of high school to graduate. A lot of that was because I just didn't have a goal in mind, so the thing that helped me was I found a way to get my high school diploma through a community college. At first, I was mostly just interested in finishing high school and exploring college outside of the high school setting. Then I happened to take a biology course where one of the tutorials was to look at pond scum under the microscope, and I was just amazed by everything that was moving and the number of species I could see. That told me I liked biology, so then I thought, how do I turn that into a career?

Initially I worked at a CVS, and became a pharmacy technician—which paid well, but did not give me as many opportunities to think critically. Then I remembered the Free Clinic of Simi Valley in my hometown that I had gone to as a kid, after my mom was laid off from her job, and thought: why don't I try volunteering there? I did and I really loved it, and had some formative experiences there. It was shortly after the 2008 recession, so there were a lot of folks who had lost their medical insurance, and volunteering gave me the opportunity to be the first point of contact for a lot of these people to get care they needed. I had opportunities to make patients feel heard and show them that I cared. It was nice to try to help people when they were so down. That experience made me interested in pursuing medicine.

 How did you become interested in pursuing research as well?

I initially got involved in research primarily to boost my application for medical school, but what I hadn’t expected was how interesting I would find the science. I transferred to UCLA after my sophomore year at community college, and then I was able to join a great lab under Kent Hill, who is a parasitologist. I found it so amazing that we could sort of peek behind the curtain and understand how genes could regulate dynamic processes, such as how the flagella can propel parasites forward. I managed to publish a co-first author paper, and then I was able to get into the MD-PhD program at UCLA.

I initially wanted to do cancer biology, but my father passed away very young from a heart attack, and it kind of changed my career trajectory. It made me realize that I was interested in studying common diseases that often involve disorders of metabolism. So, in my PhD, I joined the lab of Peter Tontonoz and focused on cholesterol metabolism. I discovered a family of proteins we call Aster proteins, which are important for moving cholesterol within cells within the body. In studying them, I realized that many of the genes we have operate only within certain contexts, like the context of being in an organ or the cell having to do something. That realization has become the main driving point for the project I'm doing now. My project is also influenced by the fact that, since beginning my fellowship in gastroenterology, I’ve seen not only that fatty liver disease is an increasingly common problem, but that the liver is really important in physiology and general health.

Putting all that together, how I got to where I am now has been a long road where I've mostly followed my nose with things that I found interesting, including how dynamic biology is and the versatility of cells, and I've picked things that I think may have a broad impact on human health.

What are your hobbies?

As a physician and scientist, it's tough to find time anymore for hobbies. I enjoy cycling and spending time with my fiancée. I enjoy history books and podcasts. It’s interesting how similar people were across all these different eras. I like what history can teach us about ourselves as human beings, and how people who were just like us dealt with different circumstances. I also think it’s cool that throughout history there are always folks who have this desire to make the world a better place, and that that’s a common part of the human experience.

The other way I spend my time is by taking care of my family farm in India that was my grandfather’s. I enjoy taking care of it, because it's a very different experience than what I'm doing as a scientist or as a physician. It's a very of-the-Earth kind of place, where things move at a slower pace, and it gives me an entirely different perspective on life. I also think of the challenges my grandfather overcame during a troubling period in India’s history, and it inspires me.

Could you say more about the experience of being at the farm?

I go there about once a year to make sure everything is running properly. The farm rotates wheat and rice mostly. Essentially, it's a large plot of land that's irrigated, and twice a year, people are hired to do the tilling and planting and harvesting. It’s pretty straightforward, but going there is also an opportunity to frequent Punjab, which is a largely rural state that both my parents are from, and where I can speak the language of Punjabi. It's a great way for me to reset and connect with my cultural roots.

One beautiful feature of Punjabi culture is the amount of time that people spend with each other that is both simple and present. Everybody is in the moment, and folks are happy spending time with each other with less pressure to always be somewhere else. I think that's the biggest reset I get there. There's less rush to go anywhere, which is, I think, quite different from my life here.

Do you collect anything?

I'm starting to collect fountain pens, primarily American made ones. I picked that up from one of my mentors in gastroenterology, Joseph Yarze. I switched to writing in cursive and I realized that I personally enjoy writing by hand. I think there's still some value to it. For me, when I'm collecting my thoughts, I find that I operate at a higher level when I'm writing than I am when I'm typing on a computer. I write better and I think better with fountain pens.

Then do you enjoy keeping a physical lab notebook?

I do. I have a small leather bound three-ring binder that I have pages in, because the binders allow you to reorganize. That's how I collect my thoughts; everything's in this physical book, and I organize it into four sections, one for science, one for medicine, one for Punjab, and one for my personal life.

Where do you see yourself in ten years?

I see myself running a research laboratory that marries basic fundamental molecular physiology with translational science. I’d want to spend about 80% of my time running the lab, really trying to understand molecular mechanisms that underlie physiology and disease, with an eye towards how those actually can translate and matter to patients. Then I would spend about 20% of my time seeing predominantly patients who have liver disease and gastrointestinal disease in the clinic. That's my ideal career.