3D Printed tumor models based on cancer tumor tissues are allowing researchers to not only understand the disease mechanism better, but also test and bring new drugs from lab to clinic faster.

Aakanksha Pathania, our next pathbreaker, Research Scientist at Novartis Institute of Biomedical Research, is part of the Oncology Translational Research team, responsible for accelerating the ‘translation’ of anti-cancer drugs from the bench to clinics (to the patients).

Aakanksha talks to Shyam Krishnamurthy from The Interview Portal about how her work on bio-fabrication of micro-devices and organoid cultures (3D mini-organs, ranging in microns) shaped her interest in personalized medicine.

For students, its one of the greatest wonders of science (Bioengineering) that we are able to mimic human body physiology through a miniaturized and simplified version of an organ !

Aakanksha, can you take us through your background?

I was born to middle-class, government-job holding parents, who had high hopes and dreams for us. My mother was a topper/gold medalist/high achiever throughout her studies, while being a hockey player (she attended national camp for team India at one point), and my father was a district/state level volleyball player. Both taught physical education to high schoolers, so naturally our parents pushed me and my younger sister towards sports (NOT!). Like any middle class Indian family, the onus was to excel in studies (especially for my father). And so, I was conditioned to be good at it since I was a child, and an elder one at that! Their dream was for us to study at this amazing ICSE certified convent school 25kms away from our home, just so we got the best opportunities at learning and speaking English. So we did. And just like my amazing mother, I tried to top my way throughout my studies while exploring every extra-curricular I could: dancing, singing, anchoring, debating, organizing. Even in sports, I used to win races, play a bit of basketball, badminton (with my father) and kho-kho (funny name, but I was pretty good at it). I could never play sports seriously since we lived far away and couldn’t make it to morning training. But I was fine with that, since most of my time was spent with my ex-army officer grandfather, who had me memorize Ramayana, Mahabharata, shlokas and all kinds of semi-imaginary stories. I credit my ability to asking questions and reading to him, something that has stayed with me all these years.

What did you do for graduation/post graduation?

As a child, I first got really fascinated with genetics when we first read about Gregor Mendel and his laws of Inheritance in Biology class. Long story short, I researched Genetic Engineering and was pretty sure I wanted to be the person to work with genomes and create superhumans (you can thank Marvel and my love of reading for this). No one in my family of teachers and army officers knew what that was, so naturally I opted for non-medical stream after my 10th, so I could crack the JEE and get into an IIT (very typical). Having left Biology behind, I thought my dream of being a genetic engineer would just be that, a dream. Fast forward to 2014, I became super anxious, didn’t sleep and crashed my JEE exam. But I somehow still cleared it, got some stupendous clarity and also into NIT Jalandhar, with Biotechnology as my major. Unsurprisingly, it was met with huge resistance from everyone I knew since no one knew what Biotechnology was, but they knew there were no jobs/future there. You could blame the Marvel-induced rebel in me, I had several options but secretly just applied to B.Tech in Biotechnology. While people took it as a last resort to get into the NIT (for the college tag), I was super interested in what I was studying from day1, always on the lookout for new projects to do and get more lab experience. The turning point was my internship at CSIR CCMB Hyderabad in the 3rd year of my undergrad. Spending 2 months working in the lab was the best time I had and I knew 2 things: I wanted to do a PhD and get out of India to do it. 

This was 2017, and as soon as my internship ended, I skipped campus placements, studied for the GRE and TOEFL for a month and gave the exam. Fast forward to March 2018, I had an admit and decided to go to University at Buffalo, NY for my master’s in Biomedical Engineering in the fall. To say my mother was surprised and/or terrified is a huge understatement.

What made you choose such an offbeat, unconventional and unusual career?

The initial spark that was Mendel’s laws of inheritance staked my curiosity in life sciences, but being from a very small town meant I had limited resources and even lesser knowledge about possibilities of a career in genetics. I loved Biology, but I didn’t want to be a doctor, just like I liked Maths and didn’t want to just be an engineer. It wasn’t until I had the choice to get a degree in B.Tech Biotechnology did I know what those possibilities could be. So, I researched what Biotechnology entailed. Turns out I could have the best of both worlds, work on interdisciplinary research projects that had the potential to impact people. It was challenging, kept me asking questions and endeavor to find answers to them.

As a result, I began reaching out to my professors at NIT about potential projects, and ended up learning a lot about Food Technology, Bioinformatics, Drug discovery and Oncology. During my internship at CSIR CCMB, I was the only undergrad intern in the research group I was assigned to, working on validating the role of a heat shock protein that gets overexpressed in most cancer types. Heat shock proteins are a family of proteins that are produced by cells in response to exposure to stressful conditions.

I’d had family experiences with elusive diseases and cancer, so the more I worked, the more fascinated I became with how ambiguous the disease mechanism is. My interest piqued with shadowing others in the lab, and the aspects they were studying to understand the disease better. And that’s how I knew, cancer research was my calling and thanks to the amazing people and the guidance at CCMB, I had a rough draft on how to get there. 

How did you plan the steps to get into the career you wanted? Or how did you make a transition to a new career? 

I’d be lying if I said everything I planned for happened in real life. I had a big picture in mind and took small, organic (and accidental!) steps to lead me to it. And I believe that it still is an ongoing process and there’s a long way to go. To think about the ‘what-next’ question, I analyze my present, heavily research into my options and just persevere to go for it.  

My first internship at CCMB was a result of countless hours of research, and the project I worked on took a lot of lab hours and researching other literature. Before that, going abroad for masters was never an idea that had entered my mind, but thanks to the experience, I realized it was an option that meant more exposure to knowledge and career opportunities. Coming back to NIT after my internship changed things for me, as people were preparing for campus placements, and I was still mentally stuck on my research in Hyderabad. So, I heavily researched again; this time it was GRE, and professors whose research I was really interested in. Fast forward to next year, I was in the US starting my master’s in biomedical engineering, developing 3D bioprinting technology and tumor models and working part-time in the campus bakery. I worked my way up to get a research assistantship with my thesis advisor, came up with my own thesis idea, and learnt new methods/techniques to execute it. 

I was about to convert my masters into a PhD, when at the penultimate moment I found out that we lacked funding. March 2020 struck, and the pandemic hit, resulting in me losing my research assistantship. I then graduated in May 2020 with my master’s degree (and a virtual thesis defense) and lost out on jobs and interview calls, being an immigrant in a highly uncertain time. 

My master’s thesis was based on developing and optimizing biofabricated 3D disease models for organoid development (a miniaturized and simplified version of an organ produced in vitro in three dimensions that shows realistic micro-anatomy) and drug testing. I had 2 projects as part of my masters thesis: Part A wherein my focus was to test and validate different drug concentrations (for cystic fibrosis) on microfluidic organ-on-a-chip device and observing how the drug affects progression of fibrosis in-vitro. Cystic Fibrosis is a genetic disease with no complete cure, so we designed this device to test fibrosis progression in the “lab-grown” human fibroblasts, so we could understand the disease mechanism better, test and bring drugs from lab to clinic faster.

Part 2 was developing organoid cultures (3D mini-organs, ranging in microns) from prostrate cancer tumor tissues and exploring their potential to form mm or cm sized, 3D bioprinted tumor models for personalized medicine. This project involved a lot of tissue engineering and biomaterial synthesis. I was synthesizing biopolymers in the lab, and observing what compositions mimic body physiology and support the cells, while also being mechanically strong to sustain 3D Bioprinting and weight of the cells. It was pretty cool, and although I couldn’t complete my goals, set the project up for future work.

It took 8 months of relentless job search, continuous networking, and hundreds of applications to get my first job as a research specialist at Merck. It was my first foray into the industry from academia, and I was working with the brightest minds to develop drug-based assays based on 3D tumoroid models. It was fast, impactful, exciting with more resources than I’d seen in academia; suffice to say I loved it. I had the most amazing mentors/collaborators and there was a lot to learn w.r.t industry dynamics, research techniques, analysis software, state-of-the-art instruments.

My job at Merck also dealt with a lot of organoid culturing, wherein instead of 3D Bioprinting the tumoroids, I was instead developing them for drug-based assays once they reached a certain appropriate size (and function). 

Soon after, I understood the dynamics better and wanted to be in a role that had a greater social/patient impact. I applied for my dream job at Novartis Institutes of Biomedical Research, transitioned into translational research in Immuno-oncology with the help from my mentor at Merck.  I’m a fierce supporter of ‘work hard and the rest will follow’ philosophy.

How did you get your first break?

Through more misses than hits!! My first break was getting my internship at CSIR CCMB in Hyderabad during my undergrad. Since that’s a story I’ve already shared previously, I’ll share the story of how I got my industry break with Merck. So, throughout my research career before Merck, I had experience working in academic labs and/or research institutes. I severely lacked industry internships/experience, which is a huge factor for getting your foot in the door, especially during the uncertainty of the pandemic. But the more time I spent job searching, the better I understood the job market. I only applied for jobs that aligned with my previous research and required niche techniques/knowledge that I possessed. I’d made it a point to expand my skill set by taking on extra projects from my advisor and collaborating on additional interdisciplinary projects with other university labs. This led to an expanded skillset, and thus widened my job pool. So, I researched companies that were working on projects similar to mine, found scientists working on those projects and reached out to them for informational interviews. With this technique, I got a couple interviews and callbacks, but due to Covid uncertainty and lockdowns, couldn’t get any job offers. I had initially applied for my role at Merck in June 2020, but after a recruiter reached out initially, I couldn’t get an interview scheduled until September 2020, when he reached out to me again. That was because (I was later told) I periodically kept following up with them for 3 months until they finally decided to give me a chance. I started working for Merck in October 2020.

What were some of the challenges you faced? How did you address them?

Challenge 1: I come from a small village in Himachal Pradesh. There’s not a lot of exposure to new interdisciplinary careers and opportunities there. My alternative was to be good at research, work hard and not succumb to societal pressures. So that’s what I did. 

Challenge 2: a consequence to challenge 1: lack of mentors. I believe I got very independent when it came to deciding my career path once I tuned societal pressures out. So it was more difficult figuring out the next steps by myself as it takes more time and effort to figure things out without someone to guide you. For example, keeping in mind our financial limitations, I applied to only public universities in the US (and just 4-5 of them). I later found out that people coached for GRE, hired advisors, and applied to more schools than I did. I also missed out on deadlines for school scholarships (for international students) that I could have applied for had I known of it. But I wouldn’t change anything in my journey, it taught me lessons that brought me here.

Challenge 3: adapting to the culture shock. I thought it was just a concept people describe with only partial truth to it. But in my quest for being independent, I struggled a lot when I first arrived in the United States. The way the society functions and how we’re brought up is very different in India vs the west. And it’d be a lie if I said being a minority and an immigrant wasn’t a factor. From managing courses, part-time jobs, and lab research, to figuring out my savings and finances: everything was new to me, I had never worked a minimum wage job or had to pay my own rent, manage my budget, pay taxes and relocate before without any help (or friends). But like previously mentioned, I wouldn’t trade the experience with anything else as I’m a better version of myself than before! 

Where do you work now? 

I currently work as a Research Scientist at Novartis Institute of Biomedical Research, which is the Innovation engine for the pharma giant, Novartis. There are 6 of these campuses across the globe, each with a different focus on addressing diseases like cancer, autoimmune disorders, cardiovascular and musculoskeletal diseases.

What problems do you address as a Research Scientist?

I’m part of the Oncology Translational Research team, wherein we collaborate with different teams to accelerate the ‘translation’ of anti-cancer drugs from the bench to clinics (to the patients). As a result, our work entails helping understand disease mechanisms from early drug discovery to preclinical studies, also studying disease target biomarkers in the patients who are part of our clinical trial. Biomarker is a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. 

So essentially my work covers understanding the impact of a drug on patient samples, testing predetermined doses, analyzing and identifying biomarkers that impact the disease mechanism and developing assays to target them. 

What are the skills needed for your role?

My work is a mix of active lab-based experiments and data analysis, and I’m learning new things every day. It requires aseptic lab technique, understanding of biology/chemistry behind the disease, assay development, molecular biology techniques and a lot of patience. In my experience, instant results are a myth: you will definitely fail a couple times before anything starts making sense. But that’s half the fun in my opinion. So, we continue to persevere, learn and explore. You get better at experimenting the more practical experience you get.

What’s a typical day like?

A typical day for me starts with meetings/brainstorming sessions with my boss and/or collaborating with teams, after which I go on-site to work on the experiments that I designed and scheduled for the day. On very busy days I’d be running parallel experiments and attending other meetings. Towards the end of the day, I either set-up another experiment or finish analyzing the previous one.

I love the constant challenge it brings me, and how there’s never a dull moment. No two days are the same, and if I’m lucky, the experiment works, and we end up with even more questions to answer. Novartis is super collaborative, so even if we don’t have any answers, we always loop other people in to suggest alternatives. Rinse and repeat. It always helps to know my work could potentially end up helping patients in clinical trials, so I think I’m making a difference.

How does your work benefit society? 

A typical drug takes, on an average, 7-10 years to be developed, approved and reach the market for patients. Behind closed doors, there’s a village that makes it possible. It makes me happy to know that I’m part of that village and what I’m doing now could help save the lives of some families. Cancer is a treacherous disease, which makes it all the more important to combat it.

Tell us an example of a specific memorable work you did that is very close to you!

I would say my master’s thesis was a rollercoaster that taught me a lot: from researching, to practically working in the lab, to handling rejections I faced on a daily basis. Having a chance to work on your original idea is very thrilling, and although I couldn’t bring it to fruition due to graduating early, there were a lot of lessons in there that have helped me maintain my curiosity and endeavor to solve problems.

Your advice to students based on your experience?

Never say never, keep pushing! In my experience, everything I’ve put my hard work and soul into has led me somewhere or taught me something. Ask more questions, and don’t be afraid to reach out to people for help. I learned this the hard way, but amidst a lot of NO’s there’d be a YES hidden somewhere. Explore more and find something that you love to do and wouldn’t mind spending 8-9 hrs every day for it. So that if you’re exhausted, let it be the good kind.

Future Plans?

That remains to be seen, but I always liked the idea of being the head of my own team  🙂 I have been mentoring and helping a lot of people on the side, so I’d like to have more and more opportunities to interact with and coach younger people (so they make better, more impactful mistakes than I did!)