Isha Jain’s lab is interested in how the human body senses and responds to variations in oxygen levels. A number of diseases, including mitochondrial diseases, strokes, heart attacks, and respiratory diseases, reflect an imbalance between oxygen supply and oxygen demand. Using a combination of systems biology, metabolism, and physiology, the Jain Lab aims to identify conditions that may benefit from “turning the oxygen dial.” A long-term goal of the team’s work is to understand the role of oxygen in aging and age-associated conditions. Using similar approaches, the lab is also investigating pathologies associated with variations in vitamin levels in the body.
Areas of Expertise
Oxygen is both vital and toxic for life. It enables efficient energy production in the mitochondria. Yet, excess oxygen leads to oxidative damage of biomolecules.
One of Jain’s seminal contributions was the discovery that in a mouse model of mitochondrial disease, lowering inhaled oxygen levels could alleviate and even reverse neurodegeneration. This finding raises the possibility that therapies aimed at “turning the oxygen dial” may benefit other mitochondrial or metabolic disorders. This work has led to a Phase 1 clinical trial.
Jain’s findings also have implications for aging and longevity. Epidemiological studies show that people who live at higher altitude—where oxygen pressure is lower—are longer-lived than people who live at sea level. Understanding the molecular mechanisms that kick in at high altitude and their interaction with the aging process may uncover new ways to alleviate age-related conditions.
Jain’s work could also lead to therapies aimed at preventing or reversing the tissue damage associated with states of ischemia, such as strokes or heart failure, where much of the pathology is due to an insufficient supply of oxygen and nutrients.
Assistant Investigator, Gladstone Institutes
Assistant Professor, Department of Biochemistry, UC San Francisco
Isha Jain is an assistant investigator at Gladstone Institutes, as well as an assistant professor at UC San Francisco (UCSF).
Jain received her undergraduate degree in chemical and physical biology from Harvard University. There, she worked in the lab of Erin O’Shea on bacterial chromosome segregation. Subsequently, she joined the Harvard-MIT Program in health sciences and technology. She earned a PhD in computer science and systems biology and worked in the labs of Vamsi Mootha and Warren Zapol, where she made the discovery that hypoxia could serve as a therapy for mitochondrial disorders. Before joining Gladstone, Jain was a UCSF Sandler Fellow.
Why Are You Dedicated to Discovery?
The feeling of discovery and solving a scientific mystery is an indescribable form of euphoria. Gladstone embodies the truly remarkable idea that we, as scientists, can understand how the human body works and use this knowledge to develop therapies.
Honors and Awards
2021 Searle Scholar Award
2021 Klingenstein-Simons Award in Neuroscience
2021 Mallinckrodt Award
2018 NIH Early Independence Award (DP5), National Institutes of Health
2018 Glenn Award for Aging Research, Glenn Foundation for Medical Research
2018–2020 Junior Faculty Grant, American Federation for Aging Research
2018–2023 Sandler Fellowship, UC San Francisco
2017 Harold Weintraub Graduate Student Award, Fred Hutch
2013–2016 Computational Sciences Graduate Fellowship, Department of Energy
2011 Barry Goldwater Award, The Barry Goldwater Scholarship and Excellence in Education Foundation
2009 Glamour Magazine’s Top 10 College Women
2008 Discover Magazine’s Top 5 Scientists under 20
2007 National Individual Winner, Siemens Competition in Math, Science, and Technology
- Coordinated transcriptional and catabolic programs support iron dependent adaptation to RAS-MAPK pathway inhibition in pancreatic cancer. Ravichandran M, Hu J, Cai C, Ward NP, Venida A, Foakes C, Kuljanin M, Yang A, Hennessey CJ, Yang Y, Desousa BR, Rademaker G, Staes AAL, Cakir Z, Jain IH, Aguirre AJ, Mancias JD, Shen Y, DeNicola GM, Perera RM. Cancer Discov. 2022 Jun 30.
- Airway stem cells sense hypoxia and differentiate into protective solitary neuroendocrine cells. Shivaraju M, Chitta UK, Grange RMH, Jain IH, Capen D, Liao L, Xu J, Ichinose F, Zapol WM, Mootha VK, Rajagopal J. Science. 2021 01 01; 371(6524):52-57.
- Turning the Oxygen Dial: Balancing the Highs and Lows. Baik AH, Jain IH. Trends Cell Biol. 2020 07; 30(7):516-536.
- Genetic Screen for Cell Fitness in High or Low Oxygen Highlights Mitochondrial and Lipid Metabolism. Jain IH, Calvo SE, Markhard AL, Skinner OS, To TL, Ast T, Mootha VK. Cell. 2020 04 30; 181(3):716-727.e11.
- Leigh Syndrome Mouse Model Can Be Rescued by Interventions that Normalize Brain Hyperoxia, but Not HIF Activation. Jain IH, Zazzeron L, Goldberger O, Marutani E, Wojtkiewicz GR, Ast T, Wang H, Schleifer G, Stepanova A, Brepoels K, Schoonjans L, Carmeliet P, Galkin A, Ichinose F, Zapol WM, Mootha VK. Cell Metab. 2019 10 01; 30(4):824-832.e3.
- Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome. Ferrari M, Jain IH, Goldberger O, Rezoagli E, Thoonen R, Cheng KH, Sosnovik DE, Scherrer-Crosbie M, Mootha VK, Zapol WM. Proc Natl Acad Sci U S A. 2017 05 23; 114(21):E4241-E4250.
- Hypoxia as a therapy for mitochondrial disease. Jain IH, Zazzeron L, Goli R, Alexa K, Schatzman-Bone S, Dhillon H, Goldberger O, Peng J, Shalem O, Sanjana NE, Zhang F, Goessling W, Zapol WM, Mootha VK. Science. 2016 Apr 01; 352(6281):54-61.
- Spatial ordering of chromosomes enhances the fidelity of chromosome partitioning in cyanobacteria. Jain IH, Vijayan V, O'Shea EK. Proc Natl Acad Sci U S A. 2012 Aug 21; 109(34):13638-43.
- A high resolution map of a cyanobacterial transcriptome. Vijayan V, Jain IH, O'Shea EK. Genome Biol. 2011; 12(5):R47.
- The making of a young scientist. Jain I, Iovine K. Dev Dyn. 2008 Jun; 237(6):1535-6.
- Connexin43 (GJA1) is required in the population of dividing cells during fin regeneration. Hoptak-Solga AD, Nielsen S, Jain I, Thummel R, Hyde DR, Iovine MK. Dev Biol. 2008 May 15; 317(2):541-8.
- Bone growth in zebrafish fins occurs via multiple pulses of cell proliferation. Jain I, Stroka C, Yan J, Huang WM, Iovine MK. Dev Dyn. 2007 Sep; 236(9):2668-74.