UNLOCKING THE GENETIC CODE TO THE HEART, LUNG AND BRAIN DEFECTS.

PROJECTS

FUNDAMENTAL mechanisms governing cellular and developmental biology of cilia

At the Kulkarni Lab, we delve deeply into the fundamental cellular and developmental mechanisms that regulate cilia formation, function, and regeneration. Cilia are microscopic, hair-like organelles present on almost all vertebrate cells, playing critical roles in sensory signaling, tissue homeostasis, and embryonic development. Defects in cilia lead to severe human diseases (ciliopathies), including respiratory dysfunction, congenital heart defects, kidney disease, and neurodevelopmental disorders.

Our research is uniquely innovative in its integration of developmental biology, mechanobiology, and cutting-edge live imaging and single-cell transcriptomics with in vivo models such as Xenopus and mouse, as well as stem cell based organoids, we uncover the new molecular pathways and cellular behaviors that orchestrate multiciliated cell differentiation, centriole amplification and cilia biogenesis. Furthermore, we explore mechanochemical signaling pathways—such as the Piezo1-ERK-YAP axis—and their roles in sensing mechanical forces and regulating cellular fate during differentiation of ciliated cells.

The significance of our research lies not only in illuminating fundamental developmental processes but also in laying a robust scientific foundation for translational research. Insights gained from our investigations offer novel perspectives into developmental biology, regeneration, and disease mechanisms, ultimately contributing towards innovative therapeutic strategies and enhancing human health.

High-throughput TRANSLATIONAL genomics of cardiopulmonary and neurodevelopmental disorders.

The Kulkarni Lab is committed to uncovering the genetic basis of congenital heart and lung diseases, as well as neurodevelopmental disorders such as microcephaly— conditions that profoundly affect millions of individuals and their families worldwide. These disorders lead to significant lifelong impacts, ranging from chronic respiratory distress and severe cardiovascular limitations to developmental delays and cognitive impairments, thereby imposing substantial physical, emotional, and economic burdens on society.

Employing state-of-the-art high-throughput sequencing and advanced CRISPR-based genome editing approaches, our lab innovatively identifies and characterizes pathogenic genetic variants responsible for these complex disorders. We leverage in vivo models (such as Xenopus and mouse), alongside stem cell based 2D and 3D organoids, to precisely model human diseases and dissect intricate molecular and mechanochemical pathways. By pioneering novel methodologies and integrative experimental pipelines, our research not only elucidates fundamental biological mechanisms but also paves the way toward transformative diagnostic tools and personalized therapeutic strategies.

Ultimately, the Kulkarni Lab aims to translate genomic discoveries into meaningful clinical applications, significantly improving patient care, enhancing quality of life, and fostering breakthroughs that can reshape clinical practices and public health interventions.

OBJECTIVES

Variant Classification: Develop robust pipelines for the functional assessment of variants of unknown significance (VUS) identified in patients with cardiopulmonary and neurodevelopmental disorders.

Gene Discovery: Identify novel genes and pathways involved in the development and function of the heart, lungs, and brain.

Translational Impact: Facilitate the integration of genomic findings into clinical practice, enhancing diagnostic accuracy and informing personalized therapeutic strategies.

COLLABORATIVE EFFORTS:

We collaborate with clinicians, genetic counselors, and bioinformaticians to bridge the gap between bench research and bedside application, striving to improve outcomes for patients affected by these debilitating conditions.