The evolution of modern Healthcare has taught us a very important lesson. Nature is always a step ahead of us and what we all need is a proactive, multi-pronged and comprehensive clinical management strategy in our fight against diseases.

 Advithi Rangaraju, our next pathbreaker, Clinical Variant Scientist, uses computational technologies such as Bioinformatics and NGS (Next Generation Sequencing) to identify genetic variants in patients that help identify causes of Genetic diseases and plan intervention strategies.

Advithi talks to Shyam Krishnamurthy from The Interview Portal about initially pursuing a PhD in Medical Genetics and subsequently applying her research background in a clinical setting by identifying correlations of a gene/variant with the patient’s observable traits.

For students, healthcare is not just about cracking NEET, its about the bigger picture of how you want to make an impact on the health of our society as a whole !

Advithi, tell us about your initial years

I was born in Hyderabad and belong to a family who served the Armed Forces. My father worked for the Indian Navy, so my initial childhood was in Lonavala and subsequently we were posted at Kerala and Vishakhapatnam, where I studied till 3rd grade in Kendriya Vidyalaya. (I studied in Central schools where ever we were posted). Later, we moved to my home town in Hyderabad, where I pursued the rest of my education. My mother is a homemaker. I have a younger brother who is a Lt. Commander in the Indian Navy. Between the two, he is the more sportive and adventurous person, but I was very much inclined towards dance and whenever I had the opportunity, I always participated in school and college cultural programs. I also took formal training in kathak (North Indian Classical dance form) for a couple of years. Apart from my job, dance is something that I have always enjoyed. I believe, pursuing a hobby helps in overall personal growth, time management skills, self-introspection and becomes a good emotional outlet. 

What did you do for graduation/ post-graduation? 

I did my Bachelors in Biotechnology, with Bioinformatics as my second major from Osmania University. In my final year of BSc, I started preparing for all the entrance exams to get into a Master’s program in Biotechnology. I secured a state 59th rank for the Osmania University entrance exam and pursued Masters in Biotechnology from Department of Genetics, OU. For my elective in the second year, I studied medical genetics. The molecular basis of genetic disorders greatly intrigued me and I decided to pursue a PhD in medical genetics. 

Following my Masters, I joined as a Project fellow in a DST (Department of Science & Technology, India) funded project and also had the opportunity to register for PhD. During my PhD, I received a Junior Research Fellowship from UGC and Senior Research Fellowship from Indian Council of Medical Research (ICMR). My research work focused on studying the genetic variants responsible for causing hypertrophic cardiomyopathy in Indian population. These variants were analyzed for pathogenicity (disease causing) by bioinformatics tools. Since I had a basic understanding of bioinformatics at undergrad level, I learned the application of those concepts for data analysis in PhD. I presented my work at several national and international conferences and have publications in peer-reviewed cardiology journals. My supervisor had been very supportive and was instrumental in developing my research interest in cardiovascular genetics. She had a well-established cardiovascular genetics lab, where I had the opportunity to study about various inherited cardiac disorders. 

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

I was always inclined towards studying biology after schooling. We tend to associate biology with becoming a doctor, but I never regretted not getting through the medical entrance. Since Biotechnology started gaining importance, I decided to pursue Bachelors and Masters in Biotechnology as mentioned above. My parents had always been very supportive. My husband, who works as a program manager in a Financial technology sector is also quite encouraging. Further, I will always be grateful to my PhD supervisor who was instrumental in raising my interest in cardiovascular genetics. I always look up to her for any suggestions and feedback. 

How did you plan the steps to get into a career you wanted? Tell us about your career path. 

After my PhD, I joined a hospital and worked as Molecular Genetic Scientist. Here, I learnt about the application of molecular genetics and cytogenetics (study of chromosomes) in clinical decision making. I had the opportunity to work with the clinicians, conceptualizing and carrying out research projects that had clinical applications. This was very different from academic research in the university. I believe, working with a clinician on a research project helps translate the research study into diagnostics. Secondly, there is vast patient clinical data available in hospitals from various departments, which can be a goldmine for designing population- based research studies. Genetic scientists can work with the clinicians to develop research studies based on the clinical data available in the hospitals. However, there are very few hospital-based research centers in India. 

Fortunately, I had the opportunity to work with a electrophysiologist (a cardiologist who is trained to treat heart rhythm disorders) and contribute to a research study on genetic variants of recurrent ventricular tachycardia in patients with post myocardial infarction in collaboration with a genetic testing company. The objective of this project was to identify genetic variants in patients with myocardial infarction who are pre-disposed to developing recurrent ventricular tachycardia (fast and abnormal heart rate). Such patients can be medically intervened by implanting a pacemaker. (Pacemaker is a device implanted in the heart to regulate the heartbeat) 

Apart from pursuing research, working in the hospital sector also gave me an invaluable experience of interacting with patients. I learned the practical application of medical genetics concepts in real life scenarios. It was interesting to know how systematic genetic evaluation, testing and pre-natal diagnosis can prevent various genetic disorders. Effectively communicating complex genetic information to help patients make informed decisions is a specialized skill, so, I decided to pursue a certification course in genetic counseling as an additional skillset. I am a certified genetic counselor with board of genetic counseling-India. This course gave me a platform to get a basic clinical orientation on various genetic conditions from other specialties as well like pediatrics, oncology and prenatal. Though I didn’t take up genetic counseling as a full-time job, this experience immensely helped me to frame and address my research questions with a clinical application. 

The initial pilot research study on the genetics of recurrent ventricular tachycardia revealed interesting results and to continue working on this project, I applied for an independent research grant and successfully received Women Scientist-A Grant from Department of Science and Technology, to pursue postdoctoral research at the Department of Molecular Diagnostics at Centre for DNA Fingerprinting and Diagnostics, Hyderabad. Here, I got an opportunity to learn about exome sequencing data analysis, variant analysis and interpretation. Additionally, I could also learn about other genetic tests that the lab offers. My postdoc mentor also had been very supportive. Unfortunately, I could not continue this project for a long time, as I moved to USA with my husband. It has been a huge change for me and a great learning experience to know how genetic testing and counseling is so well integrated in the US healthcare system with established guidelines. There are variant databases and disease registries for different genetic disorders that are useful in developing carrier screening programs (a genetic test used to determine if a healthy person is a carrier of a recessive genetic disease) and also for designing new research studies. 

Where do you work now? 

Currently, I am a visiting scholar at a genetic laboratory in Atlanta, USA. I receive advanced training from the laboratory director to understand the nuances and detailed thought process that goes into variant interpretation, before a report is generated. I work with him on exome sequencing data analysis and make clinical correlation of gene/variant with the patient phenotype. I also perform classification and interpretation of variants obtained from targeted panel testing for hereditary genetic disorders. 

Genetic testing is performed by next generation sequencing (NGS) technology. When the whole genome is sequenced, it is called as genome sequencing, when only the protein coding part of the genome (Exons) is sequenced, it called as ‘Exome sequencing’. Sequencing gives rise to thousands of genetic variants and not all variants are the cause of the condition. Each variant needs to be analyzed and then classified as ‘disease causing’ or ‘benign’. A clinical variant scientist performs this job, who is a PhD in Genetics or a related field. The genetic counselors, variant scientists work with the laboratory director to develop a genetic test report. 

I have transitioned from academic research to a clinical lab. My usual work day involves going through the data that is generated from exome sequencing and identify the variants that are disease-causing, as per the patient’s symptoms and condition. Some part of the day goes into manuscript writing for publications and reading literature. This line of work can be immensely satisfying as it is a continuous learning process and involves lot of reading. However, it also comes with responsibility and accountability, as the medical decisions that physicians and patients make largely depend on the genetic test report generated by the clinical laboratory. 

How does your work benefit the Society? 

Genetic disorders are diseases that are inherited in the family, sometimes they can be sporadic as well. It is important to understand that there is no cure for genetic diseases, prevention is the only way. Therefore, it is important to know your family history and diseases that run in the family. Presence of a variant or a mutation in the gene results in an abnormal protein function, leading to a genetic disorder. Genetic testing is a process to identify these variants for an accurate diagnosis for the patient and subsequent risk stratification in the family members. It also helps in prenatal diagnosis and family planning. Genetic testing followed by genetic counseling can help patients and their family members to make informed decisions. It also helps the physician to solve a diagnostic odyssey and come up with a better disease management plan for the patient. Due to the prevalent tradition of consanguineous marriages in India, there is a high frequency of genetic disorders. Therefore, there is a need to spread awareness on genetic syndromes among the communities. Having said that, genetic testing and counseling has begun to gain importance in most of the states in India. The technological advancements have made these tests cost-effective and accessible too. There are several companies who offer direct- to-consumer genetic testing, which can become a nightmare, if the test results are not understood properly. It is important to know the limitations and scope of a genetic test, therefore going to a genetic counselor will help to better comprehend the answers and put all the anxiety to rest. 

Advice to students. 

With so much information available on fingertips these days, there are higher chances of getting confused with several options and suggestions from family members. Therefore, it is important to know yourself, 

your interests, strengths, weaknesses, and capacities before deciding a career option. Going forward, place of internships, supervisors and mentors are instrumental in how one’s research interest and career shapes up. Research publications are very important in this field. Being at the right place at the right time sometimes does the trick. Nevertheless, trust the process of life and discover your own path! 

Future plans? 

I plan to continue in the field of laboratory genetics and aspire to pursue a fellowship program in Laboratory Genetics and Genomics.