The primary focus of my research is to identify novel hypoxia-associated markers. We examine the molecular mechanisms involved in the physiological or pathophysiological conditions caused by the hypoxic environment e.g., high altitude (Fig 1). We use both genomic and transcriptomic approaches to identify molecular markers. We have expertise to conducting functional validation studies in both in-vitro i.e., 2D and 3D cell cultures, and in-vivo i.e., fruit fly and mice, model systems. For example, from the whole-genome sequence analysis of human populations adapted to hypoxic environment of high altitude we identified EDNRB as a candidate gene associated with altitude adaptation in Ethiopian highlanders. Subsequent experiments involving mice with lower level of EdnrB (EdnrB^-/+) indicated better cardiac performance, as depicted by a 40-50 % higher cardiac output and less tissue hypoxic in these mice, in 5% oxygen environment (Fig 2). Similarly, heterozygous tropomodulin 3 (TMOD3) mice, a candidate gene we found associated with high altitude pulmonary hypertension, depicts higher pulmonary vascularization when exposed to 10% oxygen environment (Fig 3). Since hypoxia has a role in almost all major diseases e.g., cardiac ischemia, stroke, chronic lung diseases etc. our research offers significant opportunities to understand tolerance and sensitivity to hypoxic conditions and to develop novel drug targets.

Fig 1: Cover image of Mol. Biol. Evol., depicting two distinct populations, non-CMS (adapted) and CMS (mal-adapted) living at similar altitudes. A clear separation of CMS and non-CMS groups is evident from their hematocrit level and the CMS-score.

Fig 2: Heart tissue of EdnrB^+/+ and EdnrB^−/+ mice stained with hypoxia indicator pimonidazole dye (Green). (PNAS 2015)

Fig 3: Improved vascularization in the lungs of Tmod3^−/+ mice after 4 weeks of chronic hypoxia treatment. (Hum Mol Genet., 2021)