• Country: India
  • Official Title: Senior Scientist
  • Department: Genomics and Genome Biology
  • Institute: CSIR-Institute of Genomics and Integrative Biology
  • E-Mail: aastha.mishra@igib.in

Speech Title

Physiological genomics of hypoxia: How integrated omics approach delineates high altitude physiology and pathophysiology

High-altitude (HA) exposure is often unavoidable, making it crucial to understand HA adaptive and
maladaptive mechanisms. This understanding is critical to developing better therapeutic targets and inference of hypoxia response in human health and diseases. Our cross-sectional design comprising sojourners who visited HA but did not suffer from any HA-related disorders and sojourners who suffer from high altitude pulmonary edema (HAPE) upon exposure to HA, provides a chance to identify and compare acute physiological and pathophysiological hypoxia responses, respectively. HAPE is noncardiogenic pulmonary edema that develops upon rapid ascent to altitudes >2500m in otherwise healthy individuals within the first 2-5 days of HA exposure and can be fatal if left untreated. Our laboratory follows the integrated approach of whole genome cell-free DNA (cfDNA) fragmentomics integrated with the high-resolution transcriptomics data to identify the regulatory networks involved during HAPE development. The preliminary data on cfDNA observed differential cfDNA fragment patterns that correlated with peripheral oxygen saturation levels in HAPE patients. These differential patterns can further lead to a sensitive tissue-of-origin analysis contributing to the cfDNA pool for identification of significant sources of the disease-specific cell, tissue, and organ injury in HAPE patients, suggesting the potential relevance of cfDNA as a minimally invasive biomarker of inflammation, tissue injury, and cell death in understanding pathophysiological processes.