#WhyIScience Q&A: A drug discovery scientist discusses the Broad Institute’s unique role in drug development

As early as high school, Ritu Singh was fascinated by the idea of doing research at the intersection of chemistry and biology. She loved how the subjects were interconnected and, together, how they could explain biochemical pathways in the body. 

To pursue her dream of becoming a researcher, Singh studied pharmaceutical sciences as an undergraduate at the Shreemati Nathibai Damodar Thackersey Women’s University and as a master’s student at Bombay University. She then moved to the U.S. to attend Rutgers University for her Ph.D., where she studied ways to measure exposure to, and metabolism of, environmental pollutants and carcinogens.

Singh began her professional career at Merck, performing bioanalysis of pesticide residues on plants and antibiotic levels in animals, and later joined Merial (acquired by Boehringer Ingelheim) where she used mass spectrometry to study drug metabolism. She then spent several years at companies including Synta Pharmaceuticals, where she worked on early drug discovery, and Corning Life Sciences, where she worked on studies helping companies move drugs into clinical trials.

Currently a group leader in the Center for the Development of Therapeutics (CDoT), Singh works with institute scientists to help them understand the absorption, distribution, metabolism, and excretion—collectively referred to as ADME—of therapeutics under development. Her biggest challenge, she says, is developing better models and techniques using data from cell models to predict how long a compound will reside in the body, how the body will modify the compound, and what dose will be safe in animals and humans.

We spoke with Singh about her experience in industry, the challenges she sees in drug development, and her favorite parts of working in CDoT in this #WhyIScience Q&A.

What inspires you to do what you do?

Right from the beginning, I was very interested in conducting research in this area and contributing to drug discovery with a particular focus on cancer. In my career, I've worked on multiple oncology projects. Even though I may feel my contributions are modest, I'm working towards developing drugs that hopefully, one day, may help patients in need. 

Did you have any mentors who were especially helpful throughout your career?

My first mentor that I remember was my undergraduate medicinal chemistry professor, Satish Gabbe. His teaching style was really instrumental in getting me interested in medicinal chemistry. 

I also met many accomplished scientists during my career, but one that stands out was at Corning Life Sciences. I worked with a very experienced scientist, David Stresser, who taught me a lot about drug-drug interaction studies and drug discovery and development, and was key in teaching me about the studies needed for FDA approval of investigational new drugs. 

How does your work in industry compare to what you do now?

CDoT is like a biotech company within the Broad. Working at CDoT is in many ways similar to working in industry because the science behind discovering and developing therapeutics is the same. 

The main difference is that the biotech company I worked at was a medium-sized company that had maybe two or three projects at a time, and the focus was getting to a drug that would be approved by the FDA. I helped establish and validate the assays and supervised the team that executed them. At CDoT, we have 20 or 30 projects, so my role is to manage activities at multiple contract research organizations remotely to support on-going projects, with in-house activities focused on high-resolution mass spectrometry analysis. 

I enjoy meeting with different principal investigators who reach out to CDoT to evaluate the feasibility of developing therapeutics towards targets they have identified. I also have the opportunity to learn about the latest research being done at the Broad focusing on varied disease indications, which is something I didn’t have while working in industry.

What skills are necessary for success in each of these settings?

The basic skills are the same, but at smaller biotech companies, you're collaborating with fewer people. Here at the Broad, I think an important skill is being able to reach out and collaborate with multiple people. Working at the Broad has helped me enhance this skill.

In your opinion, what has been your biggest scientific accomplishment so far?

When I first joined the Broad, I realized that there was a need for scientists to understand how we integrate each step of ADME—absorption, distribution, metabolism, and excretion—early in the drug discovery process. I decided to do regular training sessions; I’d go to different groups and give a presentation to highlight the importance of ADME studies, and explain how it would help advance projects. Then I decided to talk about specific areas within ADME, like drug metabolism and transporters, and underscore the significance of using these studies to make decisions during the drug discovery process. With support of the senior leadership at CDoT, we decided to get these recorded, so they’re now a part of an online training course for Broad scientists. 

I see being able to integrate that information in early drug discovery at CDoT as a significant accomplishment. The data from these studies has helped scientists make informed decisions on multiple projects. One can look at a structure of a compound and say, Okay, this can be absorbed, or it may not be metabolized, but it's very different to actually do the study and get the data, and then make your decision. That part isn’t a black box anymore.

What is the latest trend in therapeutic development, and what trend is most intriguing to you?

I think the field’s main goal is accelerating drug delivery and development. Right now, it takes up to 10 to 15 years from the time you start developing a drug to the time you actually get approval. There are many people thinking about how we can accelerate this process. One possible solution would be using artificial intelligence and machine learning.

In my group, we use in silico modeling where we try to make predictions based on the properties of these molecules, and see how these correlate with the actual experimental values. Then we improve the models and use them to make predictions about how these molecules will behave in vivo, in mouse models or even humans. I’m also working on setting up more advanced tools for in silico prediction and am very excited about it. Incorporating this type of technology in CDoT will help advance potential therapeutics and give a much clearer picture of what can happen in the body.

What is your favorite part of your job?

I get to interact with the brightest scientists in the field on a daily basis. That's the most interesting part of my job. I'm always learning from and interacting with very accomplished people who propose the key scientific questions that we need to answer for different projects; I'm constantly learning about various areas, like target identification, computational chemistry, and x-ray crystallography. The opportunity to interact with these scientists is what I really enjoy, and I feel very fortunate to be here.

What advice would you give to someone looking to go into your field?

Always have an open mind and maintain a growth mindset. Just be curious and stay open to learning all the time. If you're that kind of person, you'll do great.