Rajesh K. Thimmulappa

ORCID: 0000-0001-6050-1323
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About
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Research Areas
  • Genomics, phytochemicals, and oxidative stress
  • Glutathione Transferases and Polymorphisms
  • Chronic Obstructive Pulmonary Disease (COPD) Research
  • Air Quality and Health Impacts
  • Neonatal Respiratory Health Research
  • Immune cells in cancer
  • IL-33, ST2, and ILC Pathways
  • Immune Response and Inflammation
  • Pediatric health and respiratory diseases
  • Respiratory Support and Mechanisms
  • MicroRNA in disease regulation
  • Bioactive Compounds and Antitumor Agents
  • Inflammation biomarkers and pathways
  • Cancer-related molecular mechanisms research
  • RNA modifications and cancer
  • Neurological Complications and Syndromes
  • Kruppel-like factors research
  • Vitamin C and Antioxidants Research
  • Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Circular RNAs in diseases
  • Retinal and Optic Conditions
  • Retinal Diseases and Treatments
  • Asthma and respiratory diseases
  • Immune Cell Function and Interaction
  • RNA Research and Splicing

JSS Academy of Higher Education and Research
2016-2025

JSS Medical College and Hospital
2021-2024

Johns Hopkins University
2008-2017

University of California, San Diego
2015

University of Tsukuba
2006

German Institute of Human Nutrition
2006

Sidney Kimmel Comprehensive Cancer Center
2006

Nuclear factor erythroid-2 related 2 (NRF2) is a redox-sensitive transcription that positively regulates the expression of genes encoding antioxidants, xenobiotic detoxification enzymes, and drug efflux pumps, confers cytoprotection against oxidative stress xenobiotics in normal cells. Kelch-like ECH-associated protein 1 (KEAP1) negatively NRF2 activity by targeting it to proteasomal degradation. Increased cellular antioxidants enzymes has been implicated resistance tumor cells...

10.1371/journal.pmed.0030420 article EN cc-by PLoS Medicine 2006-09-28

Host genetic factors that regulate innate immunity determine susceptibility to sepsis. Disruption of nuclear factor-erythroid 2–related factor 2 (Nrf2), a basic leucine zipper transcription regulates redox balance and stress response, dramatically increased the mortality mice in response endotoxin- cecal ligation puncture–induced septic shock. LPS as well TNF-α stimulus resulted greater lung inflammation Nrf2-deficient mice. Temporal analysis pulmonary global gene expression after challenge...

10.1172/jci25790 article EN Journal of Clinical Investigation 2006-03-23

Although inflammation and protease/antiprotease imbalance have been postulated to be critical in cigarette smoke–induced (CS-induced) emphysema, oxidative stress has suspected play an important role chronic obstructive pulmonary diseases. Susceptibility of the lung injury, such as that originating from inhalation CS, depends largely on its upregulation antioxidant systems. Nuclear factor, erythroid-derived 2, like 2 (Nrf2) is a redox-sensitive basic leucine zipper protein transcription...

10.1172/jci21146 article EN Journal of Clinical Investigation 2004-11-01

Although inflammation and protease/antiprotease imbalance have been postulated to be critical in cigarette smoke–induced (CS-induced) emphysema, oxidative stress has suspected play an important role chronic obstructive pulmonary diseases. Susceptibility of the lung injury, such as that originating from inhalation CS, depends largely on its upregulation antioxidant systems. Nuclear factor, erythroid-derived 2, like 2 (Nrf2) is a redox-sensitive basic leucine zipper protein transcription...

10.1172/jci200421146 article EN Journal of Clinical Investigation 2004-11-01

Electronic cigarettes (E-cigs) have experienced sharp increases in popularity over the past five years due to many factors, including aggressive marketing, increased restrictions on conventional cigarettes, and a perception that E-cigs are healthy alternatives cigarettes. Despite this perception, studies health effects humans extremely limited vivo animal models not been generated. Presently, we determined E-cig vapor contains 7x1011 free radicals per puff. To determine whether exposure...

10.1371/journal.pone.0116861 article EN cc-by PLoS ONE 2015-02-04

Abstract Nuclear factor erythroid-2–related 2 (Nrf2) is a redox-sensitive transcription that regulates the expression of electrophile and xenobiotic detoxification enzymes efflux proteins, which confer cytoprotection against oxidative stress apoptosis in normal cells. Loss function mutations Nrf2 inhibitor, Kelch-like ECH-associated protein (Keap1), results constitutive activation non–small cell lung cancer. In this study, we show cancer cells promotes tumorigenicity contributes to...

10.1158/0008-5472.can-08-1401 article EN Cancer Research 2008-09-30

Oxidative stress is a key contributor in chronic obstructive pulmonary disease (COPD) pathogenesis caused by cigarette smoking. NRF2, redox-sensitive transcription factor, dissociates from its inhibitor, KEAP1, to induce antioxidant expression that inhibits oxidative stress.To determine the link between severity of COPD, stress, and NRF2-dependent levels peripheral lung tissue patients with COPD.We assessed antioxidants, regulators NRF2 activity, damage non-COPD (smokers former smokers)...

10.1164/rccm.200803-380oc article EN American Journal of Respiratory and Critical Care Medicine 2008-06-13

Bacterial clearance in macrophages from lungs with chronic obstructive pulmonary disease is improved by stimulating the Nrf2 antioxidant signaling pathway.

10.1126/scitranslmed.3002042 article EN Science Translational Medicine 2011-04-13

Disruption of NF-E2-related factor (Nrf2), a redox-sensitive basic leucine zipper transcription factor, causes early-onset and more severe emphysema due to chronic cigarette smoke. Nrf2 determines the susceptibility lungs smoke-induced in mice through transcriptional induction numerous antioxidant genes. The Nrf2-/- have higher oxidative stress as evident from increased levels lipid peroxidation (4-hydroxy-2-nonenal) DNA damage (7,8-dihydro-8-Oxo-2'deoxyguanosine) response Glutathione...

10.1165/rcmb.2005-0325oc article EN American Journal of Respiratory Cell and Molecular Biology 2006-06-23

Sepsis syndrome is characterized by inappropriate amplified systemic inflammatory response and bacteremia that promote multiorgan failure mortality. Nuclear factor-erythroid 2 p45-related factor (Nrf2) regulates a pleiotropic cytoprotective defense program including antioxidants protects against several disorders inhibiting oxidative tissue injuries. However, the role of enhanced Nrf2 activity in modulating innate immune responses to microbial infection pathogenesis sepsis unclear.To...

10.1164/rccm.201102-0271oc article EN American Journal of Respiratory and Critical Care Medicine 2011-07-29

Nuclear factor erythroid 2-related 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes. However, where high levels are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although molecular mechanism for this defect uncertain. Here, we show that down-regulation histone deacetylase (HDAC) causes instability, resulting reduced gene and increase sensitivity to stress. Although...

10.1016/j.bbrc.2011.02.035 article EN cc-by Biochemical and Biophysical Research Communications 2011-02-13

Sepsis syndrome is characterized by a dysregulated inflammatory response to infection. NADPH oxidase-dependent reactive oxygen species (ROS) play significant roles in the pathophysiology of sepsis. We previously showed that disruption Nrf2, master regulator antioxidant defenses, caused dysregulation innate immune resulted greater mortality polymicrobial sepsis and LPS shock model; however, underlying mechanisms are unclear. In current study, compared with wild-type (Nrf2(+/+)) macrophages,...

10.4049/jimmunol.0902315 article EN The Journal of Immunology 2010-05-29

Background Oxidative stress and inflammation are two critical factors that drive the formation of plaques in atherosclerosis. Nrf2 is a redox-sensitive transcription factor upregulates battery antioxidative genes cytoprotective enzymes constitute cellular response to oxidative stress. Our previous studies have shown disruption mice (Nrf2−/−) causes increased susceptibility pulmonary emphysema, asthma sepsis due inflammation. Here we tested hypothesis Principal Findings To investigate role...

10.1371/journal.pone.0003791 article EN cc-by PLoS ONE 2008-11-21

Nrf2-mediated activation of antioxidant response element is a central part molecular mechanisms governing the protective function phase II detoxification and enzymes against carcinogenesis, oxidative stress, inflammation. Nrf2 sequestered in cytoplasm by its repressor, Keap1. We have designed synthesized novel chalcone derivatives as activators. The potency these compounds was measured expression dependent genes GCLM, NQO1, HO1 human lung epithelial cells, while cytotoxicity analyzed using...

10.1021/jm2002348 article EN Journal of Medicinal Chemistry 2011-05-03

Sepsis is characterized by an inappropriate host immune-inflammatory response and sustained oxidative damage. Nrf2, a bZIP oxidant-responsive transcription factor, regulates battery of cytoprotective genes including antioxidants maintains cellular redox homeostasis. Mouse studies have demonstrated critical role Nrf2 in improving survival during sepsis. This preclinical ex vivo study using neutrophils peripheral blood mononuclear cells (PBMCs) as surrogate evaluates the efficacy CDDO-Im...

10.1089/ars.2007.1745 article EN Antioxidants and Redox Signaling 2007-08-30

Nuclear factor erythroid 2-related 2 (Nrf2), an important regulator of lung antioxidant defenses, declines in chronic obstructive pulmonary disease (COPD). However, Nrf2 also regulates the proteasome system that degrades damaged and misfolded proteins. Because accumulation proteins endoplasmic reticulum (ER) causes ER stress stress-induced apoptosis, may potentially prevent stress-mediated apoptosis COPD.To determine whether Nrf2-regulated function affects COPD.We assessed expression Nrf2,...

10.1164/rccm.200903-0324oc article EN American Journal of Respiratory and Critical Care Medicine 2009-10-02

Chronic obstructive pulmonary disease (COPD), which is caused primarily by cigarette smoking, a major health problem worldwide. The progressive decline in lung function that occurs COPD result of persistent inflammation the airways and destruction parenchyma. Despite key role pathogenesis COPD, treatment with corticosteroids — normally highly effective antiinflammatory drugs has little therapeutic benefit. This corticosteroid resistance largely inactivation histone deacetylase 2 (HDAC2),...

10.1172/jci45144 article EN Journal of Clinical Investigation 2011-10-17
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