Tsering Stobdan, Ph.D.

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)

1. Stobdan T, Jain PP, Xiong M, Bafna V, Yuan JX, Haddad GG. Heterozygous Tropomodulin 3 mice have improved lung vascularization after chronic hypoxia. Hum Mol Genet. 2021 Oct 28. [PMID: 34718575]
2. Iranmehr A*, Stobdan T*, Zhou D*, Zhao H, Kryazhimskiy S, Bafna V, Haddad GG. Multiple mechanisms drive genomic adaptation to extreme O2 levels in Drosophila melanogaster. Nature Communication. 2021 02 12; 12(1):997. [PMID: 33579965] *Equal contributions.
3. Chapter 19, "Genetic Selection for Tolerance and Adaptation to Hypoxia". Intermittent Hypoxia: From Molecular Mechanisms to Clinical Applications. Edited by Lei Xi and Tatiana V. Serebrovskaya. Nova Science Publishers, Inc. 2011 (Hauppauge, New York 11788, U.S.A; www.novapublishers.com)
4. Zhou D, Stobdan T, Visk D, Xue J, Haddad GG. Genetic interactions regulate hypoxia tolerance conferred by activating Notch in excitatory amino acid transporter 1-positive glial cells in Drosophila melanogaster. G3 (Bethesda). 2021 Feb 12. [PMID: 33576765]
5. Chapter 21, "Mechanisms Regulating Hypoxia Tolerance in Drosophila and Humans". Stress: Genetics, Epigenetics and Genomics. 1st Edition. Editor: George Fink. Academic Press. Volume 4: Handbook of Stress. 2021 (https://doi.org/10.1016/C2016-0-04613-2)
6. Stobdan T and Haddad GG. Commentary: Novel Insight into the Genetic Basis of High Altitude Pulmonary Hypertension in Kyrgyz Highlanders. J Lung Health Dis 2019; 3(2): 29-30. [PMID: 31304480]
7. Stobdan T, Sahoo D, Azad P, Hartley I, et al. High fat diet induces sex-specific differential gene expression in Drosophila melanogaster. PLoS ONE 2019 Mar 12;14(3):e0213474. [PMID: 30861021]
8. Iranmehr A*, Stobdan T*, Zhou D, Poulsen O, et al. Novel insight into the genetic basis of high altitude Pulmonary Hypertension in Kyrgyz highlanders. Eur J Hum Genet. 2019 Jan; 27(1) : 150-159. [PMID: 30254217] *Equal contribution.
9. Stobdan T, Zhou D, Williams AT, Cabrales P, Haddad GG. Cardiac-specific knockout and pharmacological inhibition of Endothelin receptor type B lead to cardiac resistance to extreme hypoxia. J Mol Med (Berl). 2018. Sep;96(9):975-982. [PMID: 30069745]
10. Roach RC, Hackett PH, Oelz O, Bärtsch P, Luks AM, MacInnis MJ, Baillie JK, Lake Louise AMS Score Consensus Committee. The 2018 Lake Louise Acute Mountain Sickness Score. High Alt Med Biol. 2018 Mar;19(1):4-6. (Contribution) [PMID: 29583031]
11. Stobdan T, Akbari A, Azad P, Zhou D, et al. New insights into the genetic basis of Monge's disease and adaptation to high-altitude. Mol Biol Evol. 2017 Dec 1;34(12):3154-3168. [PMID:29029226].
12. Azad P, Stobdan T, Zhou D, Hartley I, et al. High-altitude adaptation in humans: from genomics to integrative physiology. J Mol Med (Berl). 2017 Dec;95(12):1269-1282. [PMID:28951950]
13. Stobdan T, Zhou D, Ao-Ieong E, Ortiz D, et al. Endothelin receptor B, a candidate gene from human studies at high altitude, improves cardiac tolerance to hypoxia in genetically engineered heterozygote mice. Proc Natl Acad Sci USA. 2015 Aug 18;112(33):10425-30. [PMID: 26240367]
14. Norboo T, Stobdan T, Tsering N, Angchuk N, Tsering P, et al. Prevalence of hypertension at high altitude: cross-sectional survey in Ladakh, Northern India 2007-2011. BMJ Open. 2015 Apr 20;5(4):e007026. [PMID: 25897026]
15. Kumar R, Kohli S, Mishra A, Garg R, Alam P, Stobdan T, et al. Interaction between the genes of vasodilatation pathways influence blood pressure and nitric oxide level in hypertension. Am J Hypertens. 2014 Aug 26. pii: hpu130. [PMID: 25159081].
16. Udpa N, Ronen R, Zhou D, Liang J, Stobdan T, et al. Whole genome sequencing of Ethiopian highlanders reveals conserved hypoxia tolerance genes. Genome Biol. 2014 Feb 20;15(2):R36. [PMID: 24555826].
17. Zhou D, Udpa N, Ronen R, Stobdan T, et al. Whole-genome sequencing uncovers the genetic basis of chronic mountain sickness in Andean highlanders. Am J Hum Genet. 2013 Sep 5;93(3):452-62. [PMID: 23954164].
18. Nejatizadeh A, Kumar R, Stobdan T, Qadar Pasha MA. GNB3 C825T polymorphism associates with plasma electrolyte balance and susceptibility to hypertension. Genet. and Mol. Biol. 2011 34(4):553-6. [PMID: 22215956].
19. Kumar S, Sharma S, Norboo T, Dolma D, Norboo A, Stobdan T, et al. Population based study to assess prevalence and risk factors of gastroesophageal reflux disease in a high altitude area. Ind. J Gastroenterol. 2011;30(3):135-43. [PMID: 21181325]
20. Stobdan T, Ali Z, Khan AP, Nejatizadeh A, et al. Polymorphisms of Renin-Angiotensin System genes as a risk factor for High-Altitude Pulmonary Edema. J Renin Angiotensin Aldosterone Syst. 2011;12(2):93-101. [PMID: 21393362]
21. Chapter 31, "High-altitude diseases: The implications of genes, genetics and drugs". Adaptation Biology and Medicine. Vol 6. Cell Adaptations and Challenges. Edited by P.S. Wang, C-H. Kuo, N. Takeda and P.K. Singal. Narosa Publishers, 2011. (http://www.narosa.com/books_display.asp?catgcode=978-81-7319-935-6)
22. Aggarwal S, Jha P, Negi S, Singh PK, Stobdan T, et al. EGLN1 involvement in high altitude adaptation revealed through genetic analysis of extreme constitution types defined in Ayurveda. Proc Natl Acad Sci USA. 2010;107(44):18961-6. [PMID: 20956315]
23. Slessarev M, Prisman E, Ito S, Watson R, Jensen D, Preiss D, Greene R, Norboo T, Stobdan T, et al. Differences in the Control of Breathing between Himalayan and Sea-Level Residents. J Physiol. 2010;588(9):1591-606. [PMID: 20194122]
24. Stobdan T, Kumar R, Mohammad G, Thinlas T, et al. Probable role of beta2-adrenergic receptor gene haplotype in high-altitude pulmonary oedema. Respirology 2010;15(4):651-658. [PMID: 20546540]
25. Nejatizadeh A, Kumar R, Stobdan T, Goyal AK, et al. CYP11B2 gene haplotypes independently and in concurrence with aldosterone and aldosterone to renin ratio increase the risk of hypertension. Clin Biochem. 2010;43:136-41. [PMID: 19786005]
26. Nejatizadeh A, Stobdan T, Kumar R, Qadar Pasha MA. Angiotensinogen gene haplotypes in hypertension. (Correspondence) J Hypertens. 2008; 26(12):2452-53. [PMID: 18475146]
27. Xing G, Qualls C, Huicho L, River-Ch M, Stobdan T, et al. Adaptation and Mal-Adaptation to Ambient Hypoxia; Andean, Ethiopian and Himalayan Patterns. PLoS ONE 2008 3(6): e2342. [PMID: 18523639]
28. Nejatizadeh A, Kumar R, Stobdan T, Goyal AK, et al. Significance of angiotensinogen gene haplotypes and genotypes combinations in hypertension. J Hypertens. 2008 June;26(6):1094-1101. [PMID: 18475146]
29. Stobdan T, Karar J and Qadar Pasha MA. High Altitude Adaptation: genetic perspectives. High Alt Med Biol. 2008 June;9(2):140-147. [PMID: 18578645]
30. Genetic landscape of the people of India: a canvas for disease gene exploration. Indian GENOME VARIATION CONSORTIUM. J Genet 2008 April;87(1) :3-20. (Contribution) [PMID: 18560169]
31. Nejatizadeh A, Kumar R, Stobdan T, Goyal AK, et al. Endothelial nitric oxide synthase gene haplotypes and circulating nitric oxide levels significantly associate with risk of essential hypertension. Free Radical Biology & Medicine 2008;44:1912–1918. [PMID: 18325347]
32. Nejatizadeh A, Stobdan T, Malhotra N, Qadar Pasha MA. The Genetic Aspects of Pre-eclampsia: Achievements and Limitations. Biochem Genet. 2008;46(7-8):451-79. [PMID: 18437552]
33. Chapter 67, "Genomics of high altitude adaptation and maladaptation". Life on the Qinghai-Tibetan Plateau. Proceedings of the 6th World Congress on Mountain Medicine and High Altitude Physiology, Edited by Ge Ri-Li and P. Hackett. Publisher - Peking University Medical Press. 2007 Page 374-386.
34. Norboo T, Stobdan T, Diskit D, Angchuk N and Kunzang M. Chronic mountain sickness in Ladakh. The Autonomic Nervous System 2007 April 44(2);71–75. [Japanese Jr.]
35. Rajput C, Arif E, Vibhuti A, Stobdan T, et al. Predominance of interaction among wild-type alleles of CYP11B2 in Himalayan natives associates with high-altitude adaptation. BBRC. 2006 Sep 22;348(2):735–40. [PMID: 16893516]
36. Stobdan T*, Charu R*, Ram RB, et al. Susceptibility to High-altitude Pulmonary Edema: Roles of ACE and ET-1 Polymorphisms. Thorax. 2006 Nov;61(11):1011-2. [PMID: 17071838] *Equal contribution
37. The Indian Genome Variation Database (IGVdb): A project overview. Invited review in Human Genetics. 2005;118:1–11. (Contribution) [PMID: 16133172]


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