This Johns Hopkins scientist and Apeejay Pitampura alumna is striving to understand how the first domino falls in congenital cardiac disorders

A Post-Doctoral researcher with the Fred Hutchinson Cancer Research Centre, Seattle, Apeejay School Pitampura alumna Dr Aditi Madan did her graduate research at the Indian Institute of Science (IISc) in Upendra Nongthomba’s lab, where she was introduced to the power of Drosophila genetics. She also explored diverse aspects of skeletal muscle biology here, and continued her research in muscle biology as a post-doc with Anthony Cammarato at the Johns Hopkins University, where she studied cardiac thin filament dynamics, and how point mutations in critical residues have a domino effect on cardiac physiology, eventually manifesting as cardiomyopathies. Dr Madan also conducted hierarchical analyses – from single molecule assays, to organ-level assays, all the way up to behavioral assays; as well as integrative studies in multiple model organisms.
When she isn’t in the lab, Dr Madan enjoys creating intricate mandalas and Madhubani art, watching stand-up comedy, and continuing her quest to find the best chicken tikka masala in the world. In a wide-ranging interview, she discusses, among other subjects, working with some of the best scientists in the world at the Indian Institute of Science and at Johns Hopkins and the Fred Hutchinson Cancer Research Centre, fond memories of the time she spent at Apeejay School, Pitampura, her love for science fiction and the intricacies of cardiac disease mechanisms. Edited excerpts:

Congratulations on making it to world-class institutions such as the Fred Hutchinson Cancer Research Centre and Johns Hopkins University. When did you develop an interest in a career in science and the intricacies of the human body and physiology?

Thank you! My earliest memory of wanting to do something in life sciences research is from fourth grade, where we were asked to write an essay on “When I grow up, I’d like to become…” in Karuna Sinha Ma’am’s class. I wrote whatever little I understood about genes, mutations, cancer, and how I would like to decode mysteries of life and, hopefully, contribute to personalised medicine. I come from a family of doctors, which played a huge role in cultivating my interest in physiology. However, I somehow could never see myself as a medical practitioner. So, when presented with the option to choose ‘Biotechnology’ rather than ‘Biology’ as a subject after X boards, I jumped at it. I am forever grateful to Ms. Dimple Sahni, who encouraged me continuously and also played a big role in helping me overcome a fear of public speaking. At home, there were always encyclopedias that I loved reading, and there was also a phase of being obsessed with science fiction novels (Michael Crichton and Robin Cook), all of which eventually manifested in my career choice.

Please take us through your academic and professional journey since the time you studied at Apeejay School, Pitampura. What is your specialisation and super specialisation?

I graduated from Apeejay School, Pitampura in 2004, after which I studied Biochemistry at Sri Venkateswara College, Delhi University. I then went on to pursue an Integrated PhD (MS + PhD) programme from the Indian Institute of Science (IISc), Bengaluru. IISc is where I was nurtured as a young scientist. I discovered my love for basic research, and how simple model organisms, like Drosophila (fruit fly), can help solve seemingly complex mysteries of life. I specialised in genetics and high-resolution imaging in Dr. Upendra Nongthomba’s lab. My PhD thesis was about proteins that make up skeletal muscle, and how these building blocks are shuffled in response to different developmental stages and/or disease conditions. I was fortunate enough to conduct two diverse kinds of studies – an in-depth investigation of a single protein – Troponin T; and large-scale genome-wide analyses of muscle mutants to explore global changes in gene expression.

Please elaborate upon your experience at Johns Hopkins University

Pursuing a doctorate from a prestigious institution like IISc provided the necessary exposure to interact with scientists from around the world. One of my early mentors was Dr. John Sparrow from the University of York, who was instrumental in my move to the United States. He introduced me to Dr. Anthony Cammarato from Johns Hopkins University (JHU), who I met at a conference in Washington DC. His research is centred around muscle mechanics and congenital cardiomyopathies, which was exactly what I wanted to delve deeper in as part of my postdoctoral research. I investigated cardiac disease mechanisms from the level of single molecules all the way up to behavioral assays, and conducted studies in multiple model organisms (Drosophila, guinea pig, rat) to validate findings across different species. To do so, I used cutting-edge technologies like CRISPR and high resolution confocal and electron microscopy. My experience at Johns Hopkins University helped me develop a solid work ethic, inculcate a scientific temperament driven by rigor, and understand the value of effective scientific communication. I had the opportunity to collaborate with leading scientists all over the world, and travel a lot as well (pre-Covid) to do the necessary experiments for our projects. I got to present my work at numerous meetings, and the acknowledgment and awards from those have been instrumental in shaping the research we did.

What is your current job profile at the Fred Hutchinson Cancer Research Centre?

At the Hutch, I am working with Dr. Akhila Rajan, and studying the effects of fat physiology on immunity and brain function. We are looking at interorgan communication, and how metabolic dysregulation can impact brain function, cognition and immunity. This is a gear switch for me, both in terms of the question being asked, as well as the scientific approaches being undertaken. I am excited about exploring a whole new aspect of physiology that would contribute to our understanding of obesity and other metabolic disorders.

What role can genetics and genomics play in the diagnosis and treatment of life-threatening ailments such as cardio-vascular diseases and cancer?

As of today, when a patient walks into a clinic with congenital cardiac issues, most of the damage is already done, and the physician’s role is either symptomatic relief and/or surgical intervention. As basic researchers, we are striving to gain a deeper understanding of how the first domino falls when there is a mutation in an important gene, leading to production of a faulty protein, that will then interact aberrantly with its partners, and cause a cascade of abnormal events inside the heart. This information will put us in a better position to do prenatal screenings, and hopefully do the necessary therapies to limit and/or reverse the damage. These sound like pipe dreams, but could be potential life savers in the near future.

What are your memories of the time you spent at Apeejay School, PItampura? Any faculty members that you remember in particular?

I have a treasure trove of good memories of my time at Apeejay Pitampura. I made friends for life there, and we still stay in touch despite time zone differences and a global pandemic. I am grateful to all my teachers, particularly Ms. Soorma, Ms. Upma Raizada, Ms. Vandana Arora, Ms. Malini Sridhar, Mr. Jacob, Mr. Arvind Kaushal, Mr. Chauhan, Mr. PC Verma, Ms. Ritu Lakra, Ms. Karuna Sinha, Ms. Dimple Sahni, for playing such an integral role in molding me to be the person I am today. It’s been a wonderful schooling experience, where I have only the fondest memories. The annual day preparations used to be the highlight of the year for me. Other than that, the annual excursions to the hills are also cherished and discussed when I meet up with school friends.

Did you pick up any life lessons that helped you in your career?

It’s hard to pick one! I attribute my love of learning to the school. There was constant encouragement, inculcation of deeper values of being a good person, exposure to extracurricular activities for holistic growth, and a very comfortable teaching environment that felt like an extension of home to me. For all that, I will always be indebted.

 What are your future plans? Would you stay in academia or become a medical practitioner or scientist at a renowned hospital?

I intend to continue my career in scientific research. I am open to pursuing it in academia or industry, as the main attraction for me has always been the process of experimentation, hypothesis-testing, troubleshooting and problem-solving. I am open to doing so wherever good opportunities present themselves.