Ankit Gilani

What led you to your current position as a postdoc?

I am originally from India. To be honest, I never thought I would end up in research. I did my Master’s in pharmacology and toxicology at the National Institute of Pharmaceutical Education and Research in India. After that I took a job at a pharmaceutical company, but it was an office job and very repetitive. I got bored after about six months of doing the same thing every day, so I started to think about going back to the lab and was excited thinking about the momentum of doing something new every day and making new discoveries. I applied for PhD programs and got selected by New York Medical College, in upstate (Valhalla) where I did my PhD in pharmacology. My thesis project was in obesity and diabetes and we were studying insulin signaling in adipocytes and also insulin secretion in pancreatic beta cells. I wanted to stay in the research area, so in my postdoc search I looked for labs doing work along similar lines. I entered the keyword “obesity” on the Science Careers website and at the time only one lab was hiring, which was my current lab (the Lo lab) at Weill Cornell Medicine. I interviewed, got selected, and started my postdoc here in December of 2019.

What research project are you most excited about right now?

My work focuses on a gene called Fam20C, which is a protein kinase enzyme that gets upregulated in fat cells making it very relevant for obesity. I’ve been interested in this gene from the beginning of my postdoc, particularly what it might be doing in other organs. Our lab has expertise in working on pancreatic beta cells, so soon after I joined I started working on developing a mouse model in which I could knock out Fam20C specifically in beta cells. It took almost an entire year to develop the mouse model and grow the colony, but we are now able to selectively knock out Fam20C in beta cells. We are seeing some cool data so far. Fam20C is an endoplasmic reticulum (ER) Golgi pathway protein that is important for secretion of insulin, so it’s likely to play a major role in how insulin is processed in the pancreatic beta cell granules and then how it is secreted. This started out as a side project, but my PI has allowed me to continue with it and I’m really excited about where it’s going.

Our work has huge translational implications for obesity and diabetes. Obesity especially, which has already been declared an epidemic in the US and globally. Currently, all the treatments that are directed towards obesity are related to controlling the diet or attempting to disrupt pathways involved in consuming or metabolizing food, but these can have a lot of unwanted side effects. For example, there are drugs that may block absorption of fat, but these kinds of drugs also block absorption of other molecules like fat soluble vitamins which are useful for your body. In contrast, our data so far is showing that our molecule is very specific. What we have seen is that Fam20C gets specifically upregulated in fat cells during obesity whereas it stays normal in other cells. We are in the process of developing specific inhibitors of this enzyme which we can then direct specifically to fat cells. The end goal would be to develop an inhibitor that we could inject, in mice first and then humans, which could reverse or promote fat loss.

What tools and techniques do you use in your research?

We use a lot of transgenic mouse lines, in which specific genes are knocked out. Another technique we use regularly in the lab is performing differentiation of preadipocytes. These are stem cells which are part of the adipose tissue, but they can be differentiated into fat cells. We isolate adipose tissue from mice or humans, then isolate stem cells (i.e., preadipocytes), then there is a 1-2 week time course during which the cells are differentiated into adipocytes. We start from a fibroblast and at the end we have a cell loaded with fat. It’s cool to see how cells transform from day to day and eventually develop a huge bulge towards the end of the process, with the cell nucleus squished on the side. We use this differentiation technique for both mouse and human preadipocytes and see species differences. In mice, the adipocytes are smaller whereas in humans they get huge with large lipid droplets. Using this technique allows us to address our major questions about the role of Fam20C within different types of cells. One thing we are interested in is whether or not this gene gets up-regulated during the differentiation process. In addition, once we differentiate the cells, we knock our gene out and see what other genes are affected as a result. In other words, what are the downstream effectors. We are seeing beneficial effects of knocking out Fam20C in mice, but we are interested in looking more at the cellular level to establish what the mechanism of these benefits is.

What resources do you use from Weill Cornell?

One of the resources we regularly take advantage of is the confocal microscopy core. It’s really easy to use the core and the people that work there are really nice. For my main project I am trying to visualize the localization of the Fam20C molecule in the cell. Until recently, it had only been documented to be in the ER (golgi pathway, secretory pathway). However, we’ve found that the gene also has a nuclear localization sequence, and the enzyme is present within the nucleus. Confocal microscopy has been an especially nice tool to have for this project. It has allowed us to record a 3-dimensional video of the nucleus where we can see that our protein of interest is actually embedded deep within the nucleus. Another tool we use is the mass spec core. As a Kinase, Fam20C phosphorylates a number of substrates, and using mass spec we have been able to identify some of the major targets, which we think are critical substrates to promote disease progression after being phosphorylated.

What are your career plans?

I am keeping my options open, but my primary goal is to have my own lab. I would like to stay in the field of obesity and diabetes. I started in this field during my PhD and then was fortunate to find a postdoc also in the same area. Going forward it would be great to make use of the knowledge and expertise that I've gained during these many years. I also have a personal interest in this research area. My grandmother passed from uncontrolled diabetes and my dad has uncontrolled diabetes right now. So, I'm aware that some of my own genes get switched on at some point and I am at risk for diabetes. It motivates me to work along those lines and find a treatment before it happens. To set myself up to continue in academia the obvious next step is to become an instructor or assistant professor, and then launch my own independent lab. On the other hand, these days there are many industry careers that allow you to conduct your own research and industry labs where the culture is very similar to that of academia - but you don't have to worry about funding, so that would also be a good option. I would like to stay in New York if possible. I love this area and the Northeast region, so I'm hoping to stay here, but again I am keeping my options open.

What is the best part of being a postdoc?

There are many great parts but the best part for me is the independence that you get, compared to grad students, technicians, or even staff scientists. Postdocs can design their own experiments and generate their own hypotheses. We get a level of independence in our research that allows us to pretty much choose what we want to work on depending on our area of interest. There are no limits to what someone can achieve with that independence. That’s my most favorite part.

What advice would you give incoming postdocs?

I would advise incoming postdocs to know what your collaborators are working on, know what other techniques you could use outside of your lab, or what’s accessible to you, and make use of all the facilities. Not a lot of postdocs know that we have so many incredible cores that we can take advantage of for projects. I got to know them slowly through my boss and other colleagues, but it would have been nice if I would have known in the early stages of when I was planning my project that we have the mass spec core, the confocal core, and many others.

I would also say to incoming postdocs, and this is advice that I received from my PhD mentor, try not to do science with blinders on. Don’t just look in one direction when you get your data, try to look at it from all different angles. I think that’s very important. Many new postdocs when they come in have one hypothesis and do all their work trying to pursue that one direction. Then, if it doesn’t work out, they get stuck and have trouble approaching it from another perspective. So, I would encourage new postdocs to try to see things from a different perspective and try to reimagine things and get creative with their projects.

What was your experience with Postdoc Research Day 2020?

When I saw the email I thought it sounded cool and I had sufficient data at that point to give an oral presentation so I signed up. I think it was a really nice experience to present. My presentation was on a project a bit different than what I am working on currently, although also related to the Fam20C gene. At the time, I was working from the point of view of fat cells rather than pancreatic beta cells. We had seen that knocking out Fam20C in adipocytes leads to a protection from obesity from high fat diet consumption as well as an absence of insulin resistance in mice (i.e., mice are sensitive to insulin). We are still continuing this work, to establish the signaling mechanism. After my presentation, the questions I got were really useful for me later on. Some of the questions I would have never thought about if I didn't present. One question was about looking at human data on genome wide association studies (GWAS) for my gene, which is something we had never done, but after Postdoc Research Day we went on to look at human genome wide association sequences for our gene and actually found some really interesting upregulations in several diseases. Outside of my presentation I think the whole experience was very smooth. Because of Covid there was a hybrid format. So, I presented on zoom, but from an auditorium with other presenters. I would like to thank the entire PDA for doing such a good job organizing and uniting the postdocs.

What is your favorite thing about living in New York City?

I think the thing I like the most about New York is the diverse cultures it brings together. It's like visiting the whole world in one city. You have people from all different cultures, you have restaurants from all different cultures, you can experience anything. I'm a big foodie and I like to explore different cuisines. The kind of cuisines I’ve been able to explore in New York - I don't think I would be able to explore anywhere else in the United States. One of my favorite restaurants is Xi'an Famous Foods, which is near Weill Cornell. They have spicy cumin lamb noodles on their menu which I highly recommend, although it’s only for those who have a little bit higher spice tolerance.

What hobbies do you enjoy outside of the lab?

I like to play tennis and that’s what I usually do on the weekends. I feel like tennis is a complete workout, so I don’t need to do anything else. I just play tennis for a couple hours and it keeps me fit and keeps me going. I also like hiking and going out to explore nature. I know a few good hiking spots a bit more upstate, near New York Medical College where I did my PhD, so I usually go around there.

If you weren’t a scientist, what would you be?

I think I would be a photographer if not a scientist. I’m a very amateur photographer, I don’t use a fancy camera to take pictures, but I like to see things from different perspectives. When I take pictures, I take the same picture in many different ways and then present the series to my friends to show how things can be seen from different angles, making them more appealing, or bringing out the expression in a specific scene, or person, or image. There’s some similarity between that and science too. In science we often need to see things from different perspectives. People who hone in on one hypothesis to drive their research can get stuck in the same idea. You have to try and see your research from all different angles. Whatever data you get, look at it one way, and then look at it another way - it makes research more interesting.

What are you most looking forward to in the upcoming year?

For my research, I’m looking forward to getting some cool data from the project where we are trying to see the effect of our gene of interest on insulin secretion. I’m hoping we get data in line with what we’re expecting, but even if not, any data will help me advance the project from a different perspective. Outside of science, I’m really looking forward to getting to life without masks on. It’s been so long. We had it for a short period of time and now we are back to masks. I hope people get vaccinated as soon as possible so that all of us can get our masks off.