Noopur Khobrekar Is Tackling All The Genetic Questions Of Autism Spectrum Disorder

When NYSCF – Druckenmiller Fellow Noopur Khobrekar, PhD, reflects on her career in research, she recalls an early fascination with how much our cells can do. 

“When I first learned that every cell in our bodies is doing all these complex functions, just to let us go about our day without a hitch, I found that mesmerizing,” she says.

Now a postdoctoral fellow in Lorenz Studer’s lab at Memorial Sloan Kettering Cancer Center, she has turned her attention to what happens when our cells falter, specifically in disorders like autism. 

Hear from Noopur about why stem cells are important for understanding disorders of the central nervous system, the power of team science, and why she’s excited to join the NYSCF Innovator community.

What made you want to become a scientist?

It’s funny to think back to what got me interested in science because I feel I’ve been on this journey for so long. When I was in middle school, I first learned about human genetics and the basics of cell biology. The human body is such a well-oiled machine, but when that machine breaks, we get disease.

So to me, the question was how can we better understand biology so we can identify when it goes wrong. This potentially gives us opportunities to develop treatments for diseases that we haven’t defeated yet. And the best way to address this – even today, I believe – is to become a scientist. 

What made you interested in stem cells?

I’ve always wanted to study human diseases in human cells. We have postmortem tissue available to us in biological research, and that can give us a valuable snapshot into disease pathology, but it’s still difficult to tease out underlying mechanisms of pathogenesis from just that.

And when I was working with animal models, I found myself questioning how relevant the findings were to humans. These in vivo studies certainly have many perks, but combining that with stem cells can help eliminate some of the doubt as to how translational a finding may be.

Stem cells have a very unique potential to make any kind of cell. You can manipulate those cells genetically or environmentally so that they mimic a disease state, and you can even tailor them for use in regenerative therapies. Altogether, this opens up so many possibilities for biological research. 

What made you want to study autism?

Considering the field of research, I feel there are many degenerative and developmental disorders of the nervous system for which we know quite a lot, but we haven’t really gotten to the point of ameliorating the symptoms for patients in the clinic. There’s a lot of information about the brain, but it is still a very enigmatic organ system for us, and I’ve been fascinated by it for years.

Autism, specifically, is a spectrum disorder – it carries many different flavors that are hard to characterize. We may know the genetics [of a patient], but it’s very hard to match them up [with disease characteristics] to figure out what’s going wrong in individual patients. 

If we look at the incidence of autism – it’s very high. Roughly one in 50 children in the United States have the disorder and it’s a social burden. No matter how hard we try to help these children through school and beyond, they’re not always getting the best standard of life. So if we can somehow help them by treating some of the aspects of this disorder, I think it’s totally worth it.

How does your lab use stem cells to study autism?

We are taking more of a cellular approach to autism. We are using stem cells to make the different cell types of the human brain: neurons and glia [support cells in the brain]. And the reason we do this is because when we look at what’s known about the pathology of autism, we see that both the neurons as well as the glia are affected in patients. And depending on the genes that are affected in a patient, different cell types may exhibit the pathology. 

So once we use stem cells to make these cells of the brain, we’ll manipulate them genetically to model high-risk autism genes. This will help us understand which functions at the cellular level are going awry that are leading to the clinical symptoms in patients.

What do you hope to achieve in your career in research?

I’m still at a stage in my career where I feel there are infinite possibilities, and I have been fixated on the nervous system for a while now. When I decided to work with autism, I did so because it’s an interest that I would like to pursue for a while. 

The first step, I think, is to put together the human genetics to address the cellular functioning and to stratify the clinical data, which would help us understand how different autism genes are  contributing to pathogenesis across patients. Then we have to dig deeper into the cellular mechanisms that are affected in these cohorts of patients. Once we know the underlying mechanisms, we can hopefully identify targets that are druggable. 

It’s kind of a multi-step roadmap, and I hope that someday in the future, I will be able to present a body of work which might help improve the lives of individuals – no matter how small that group may be.

What advice would you give to young people who are interested in pursuing STEM?

The truth is research will always take quite a lot of time and you will hit roadblocks – maybe technical or conceptual, or sometimes just practical – so I think it’s important when you come to that phase to dig in your heels and not give up. When you’re at the bench doing an experiment, sometimes you get so fixated on the little bits of the project that you tend to forget the ultimate goal. So I would just tell the young people to try to figure out a question that really fascinates you, and then keep that at the back of your minds while you do all the little daily things. That way, even if you get stuck, you have the motivation to drive you on and find a way.

Can you talk a little bit about the role of diversity, equity, inclusion, and belonging (DEIB) in STEM and how you’ve seen its importance throughout your career?

I’m fortunate to be in science at a time where we are actively talking about DEIB, and I personally believe that talent or brilliance doesn’t have a race or a gender or ethnicity. So if we want to solve the difficult problems, we need to give an opportunity to all the brightest minds that are out there. 

I’ve been personally very fortunate that I’ve worked closely with mentors, who as a woman of color, never really gave me a second citizen treatment and who gave me credit for my work and acknowledged my efforts. And that’s why I think I’m here today, still in the field. But I’m also acutely aware that that might not be the case for everybody. And some people might feel like giving up when they do not get that breakthrough and get to showcase their skills. I think it’s critical that we talk more about it, and that we try to understand it better. And then I really hope that at some point in my career, there will come a time when we don’t have to talk about DEIB anymore because it will be so ingrained in each and every one of us. It will become second nature, and we won’t look at people differently based on what they represent. 

What is most exciting to you about receiving the award and joining the NYSCF innovator community?

NYSCF has played a critical role in funding unconventional work from trailblazing researchers. To even have my work recognized by NYSCF is the ultimate honor and gives me a lot of hope for this project. 

Secondly, I think we all would agree that you can’t really do good science in isolation. It’s always a team exercise, and it’s super important to have people with whom one can discuss challenges and ideas. Doing this as a part of the NYSCF Innovator community is a real privilege and I’m really excited to hear from this outstanding community about how they approach science and their vision for the field. 

Now I’m looking forward to diving in and doing the hard work, and hopefully having some exciting insights to share in the future!