Faculty focus on Karthik Shekhar

Karthik Shekhar is an assistant professor in the Department of Chemical & Biomolecular Engineering. Shekhar’s lab is broadly interested in gaining a molecular understanding of cellular diversity in complex tissues, as well as investigating its developmental and evolutionary origins, and its biological consequences for tissue function and degeneration. They use high-throughput single-cell genomic measurements to understand cellular diversity in the mouse visual system and explore their conservation in other vertebrates, including humans and non-human primates. More recently, his group has also become interested in the electrochemical aspects of signal propagation along neuronal membranes.

QB3-Berkeley: What’s an exciting question or challenge that your lab is trying to answer?

Karthik Shekhar: Our lab is interested in neuroscience, and we take an interdisciplinary approach to address a variety of questions in basic neurobiology. Over the last few years, we have focused our efforts on understanding the genomic basis of neural diversity in the part of the brain that is involved in visual processing, or what’s called the visual system.

One area of recent focus is the evolution of neural diversity. If you look at the retina of any given vertebrate species, it is extremely diverse in terms of the shapes and forms of nerve cells that exist in the tissue. We’ve systematically classified this diversity in mice; we also classified this diversity in primates. But then the question is, how are how are those two interrelated? Can you map the diversity in one animal to the diversity in another animal? Now, this is an interesting question from the point of view of basic science, because ultimately, the types of neurons that exist within our retina are involved in processing the visual signals that we care about from the environment. And there is nothing to say that that should be the same in a mouse, which has a very different visual behavior than primates. Mice also don’t rely a lot on color vision the way we do.

The Karthik Shekhar lab members stand in front of a pool.
The Karthik Shekhar lab. Photo courtesy of Karthik Shekhar.

This is also important from the point of view of translation, because if we are to develop animal models for eye diseases, we need to understand to what extent cell types in those models are conserved with humans. We took upon this challenge of reconstructing the evolutionary interrelationships across the retina of different species—with a focus on cell types. We use data-driven approaches—mostly different types of single-cell genomic technologies (transcriptomics and epigenomics)—that allow us to measure the molecular fingerprints of many neurons. We then use computational methods to study how these neurons are connected across different species. The challenge, of course, is that in evolution is you can’t go back in time and figure out what happened. A lot of that must then involve guesswork and inference based on data that you have at your disposal, which is the animals that exist today.

QB3: Your research has been featured in Berkeley News and you’ve worked with science writers to communicate your labs work to the public. Why do you think it’s important for scientists to share their research with general audiences?

KS: Science communication allows a general audience to see a glimpse of what the scientific process is like, and why basic science is so important for human progress. It’s the engine of discovery, whose dividends may not be obvious in the near term. For translational questions, on the other hand, it gives scientists an opportunity to communicate a study’s immediate impacts, which is also equally important. Ultimately, in any advanced society, the general public must be invested in supporting scientific efforts. Furthermore, communicating our work to the public can serve to inspire students to pursue science.

Science communication also offers the opportunity for one to clarify one’s own thinking, when one has to describe a scientific discovery to a general audience in an accessible way. That forces you to think from the simplest point of view. Of course, simple does not imply easy. That process is important for any communication, whether it’s in my lecture hall or on Berkeley News, because people are a lot more fascinated with something when they actually understand it.

QB3: What did you want to be when you were growing up?

KS: I grew up in India, and there was nobody in my immediate family who was a scientist. I grew up being inspired by scientists like Marie Curie, Einstein, or Newton, but they seemed very distant to me. I wanted to be various things when I grew up: an actor or a writer or earn an MBA and start my own company. The undergrad experience was formative for me; it was the first time I got to conduct research with a professor. For the first time, I felt like I could do science. Before that, it was not even conceivable for me to think I could become a scientist.

QB3: What advice would you give to students who are interested in your field?

KS: One has to find one’s own path; there is no template. But the first thing is always to get excited about something. A passion for the work is what sustains you for the long term. Despite the changes that are coming in the way we do science, it’s still a monastic enterprise: You have to come up with your own ideas and convince others of those ideas.

Also important is finding the right mentor and environment. Find a mentor who really cares about your intellectual growth, and who’s willing to spend time with you and talk to you and listen to your ideas rather than assigning you to a track, where you’re left on your own. Also, one must train deeply and understand the importance of building a broad foundation. I’m not doing the type of research that I was trained in as a PhD student, but I felt confident changing directions because I knew I could learn something new.

Finally, you need to make a choice. It may not be the perfect choice, but you have to make it and focus your energies into that choice. As humans, we overestimate what we can accomplish within a day or a week, and we underestimate what can be accomplished over years. You have to give your work that time and persistence.

QB3: What brought you to UC Berkeley and what do you like best about Berkeley?

KS: Like everybody else, I applied to a bunch of places, and I interviewed in a subset of those, and a smaller subset of those that interviewed me made me offers. In fact, I was not confident in getting an offer at Berkeley because I was applying to an engineering department. My research had not been in engineering, so I had not imagined that I would get an offer from Berkeley. But when I did, it was a quick decision.

Now that I’m here, I like what a colleague of mine says about Berkeley: It’s the most laid-back intense place. At Berkeley, we’re given the freedom to be to be independent—nobody tells you what to do. Other faculty, including senior faculty, are extremely supportive. And you can approach anyone for advice.

I was attracted by the intellectual environment at Berkeley. We take education seriously. We keep the focus on where it matters the most, which is science. I feel at home here. It’s an amazing melting pot of so many diverse research disciplines. Even though I’m in chemical engineering, I have close interactions with neuroscientists and some computational biologists and physicists, which makes research and discovery very exciting. In the words of Kurt Vonnegut, “If this isn’t nice, what is?”