Dr. Dhandapany Perundurai

Dr Dhandapany Perundurai is a full faculty (Scientist F and Associate Professor) at the inStem, Bangalore having more than 24 years of research experience in the field of human genomics, stem cells, and animal models of cardiovascular diseases. Dr. Perundurai earned his MSC and PhD degrees from India in 2000 and 2008 respectively. He completed his post-doctoral training at Mount Sinai School of Medicine, New York City and was promoted to Instructor in Pediatrics 2014. He joined inStem and Oregon Health and Science University, Portland, USA in 2015 as a joint Assistant Professor and as an Associate Professor/ Scientist F from 2022. Despite holding a prestigious tenured faculty position in the United States, he made the bold and commendable decision to join inStem, driven by a profound commitment to tackle the pressing cardiovascular challenges facing the Indian subcontinent. This move underscores his dedication to making a significant impact where it is most needed, demonstrating a visionary approach to fill the gaps in global health issues.

Dr Perundurai is interested in identifying novel genes, mechanisms and drugs for cardiovascular diseases using a multi-model approach involving various model organisms. He is an expert in cardiac genomics, stem cells, organoids, gene editing, and animal models.

Cardiomyopathies are one of the well-recognised genetic diseases, and their delay in diagnosis will lead to sudden cardiac death, heart failure and impair the quality of life. Understanding genetic causes will help in early identification and planning appropriate treatment strategies. However, a significant number of patients’ genetic studies reveal the absence of reported cardiomyopathy-related pathogenic gene mutation, suggesting that novel disease-associated genes remain to be discovered hampering correct drug choice.  Dr Perundurai’s research program-1 is geared to bridge these gaps. To achieve this program, Dr Perundurai collaborated with various clinicians across the country to collect patients’ samples. Using the patient clinical samples and newer pipeline, Dr Perundurai’s lab have discovered various novel genes published these in International reputed journals. He has more than 40 papers in various prestigious and reputed international journals including Nature Genetics, Proc Natl Acad Sci (PNAS) USA, Science Advances, Cell Reports, European Molecular Biology Organization (EMBO), IScience, NPJ Genomic Medicine, Journal of Medical Genetics (JMG), Stem Cell Research, Journal of Clinical Investigation (JCI) Insight, Journal of the American Heart Association (JAHA) etc. His laboratory discovered several new genetic risk factors for cardiomyopathies, such as RPS6KB1, TTL, and NRAP, and identified ADIPOR1 as the first genetic link shared between cardiomyopathy and diabetes. To enhance the potential for discovering new genes and conducting ethnic-specific comparisons, Dr. Perundurai's lab developed an Indian healthy aging reference genome dataset known as i-DHANS.

The discovery of novel genes opens up new avenues for investigating the molecular processes involved in human heart disease. Dr. Perundurai's research initiatives, specifically programs 2 and 3, focus on understanding the global mechanistic connections and identifying therapeutic targets. In program 2, his laboratory employs a range of pre-clinical model systems, such as patient-specific induced pluripotent stem cells (iPSCs), human cardiac vascularized organoids (hcVO), and genetically altered flies and mice. These models are used alongside advanced techniques like CRISPR-Cas9 gene editing, confocal and electron microscopy, global and single-cell transcriptomics, and 3D bioprinting. Functional studies that link gene variants to disease phenotypes further facilitate drug discovery. In program 3, drugs targeting the underlying mechanisms are tested in these models to evaluate their effectiveness in reversing phenotypes. Through these approaches, Dr. Perundurai has demonstrated that each new gene relies on distinct signaling pathways leading to cardiac hypertrophy, highlighting the significance of gene-based treatments for cardiomyopathies. Furthermore, program 4 in his lab examines how lifestyle factors, such as sleep and diet, influence the progression of heart failure.

Dr Perundurai is a recipient of various national and international awards and fellowships including DBT, DST-SERB, ICMR- rare disease challenge grant, Biotechnology Industry Research Assistance Council (BIRAC), Anusandhan National Research Foundation (ANRF), Ramanujan fellowship, American Heart Association (AHA)-Scientist Development Award, Wellcome Trust fellowship, Centre Franco-Indien pour la Promotion de la Recherche Avancée (CEFIPRA), AHA International Professorship Award etc.