725 N Wolfe Street
Baltimore, MD 21205
Redox regulation plays a central role in signal transduction processes operating in the brain. Aberrant redox signaling is a hallmark of several neurodegenerative diseases such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis and various Ataxias. It is becoming increasingly clear that redox imbalance contributes to disease progression and pathophysiology of these diseases. My laboratory studies the molecular mechanisms underlying redox homeostasis in the brain with a focus on signaling mediated by gaseous messenger molecules such as hydrogen sulfide (H2S) and nitric oxide (NO). H2S and NO signal via post-translational modifications, on reactive cysteine residues, termed persulfidation/sulfhydration and nitrosylation respectively. We also study signaling mediated by redox active small molecules (bilirubin, cysteine, cysteamine, NAD+ and glutathione) and associated enzymes. Most recently we have been studying redox signaling in myalgic encephalomyelitis/chronic fatigue syndrome and COVID-19. Using cell culture, mouse models and patient samples, we have shown that modulating sulfhydration and nitrosylation networks have therapeutic benefits. These studies have yielded important clues that may be harnessed to develop novel therapeutics that delay, halt, reverse or better still, prevent neurodegeneration.
Paul BD*, Lemle MD, Komaroff AL and Snyder SH* Redox Imbalance Links COVID-19 and Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome. Proc Natl Acad Sci USA. 2021. (*Corresponding). Aug 24;118(34):e2024358118. doi: 10.1073/pnas.2024358118. Study highlights possible link between ‘long’ COVID-19, chronic fatigue syndrome – UPI.com
Giovinazzo D, Bursac B, Sbodio JI, Nalluru S, Snowman AM, Whiteman M, Filipovic MR, Snyder SH* and Paul BD*. Hydrogen sulfide mediates neuroprotection in Alzheimer’s disease by sulfhydration of GSK3β and inhibition of Tau hyper-phosphorylation. Proc Natl Acad Sci USA. 2021. Jan 26;118(4):e2017225118. doi: 10.1073/pnas.2017225118. (*Corresponding). PMID: 33431651. Rotten Egg Gas Could Guard Against Alzheimer’s Disease (hopkinsmedicine.org)
Vasavda C, Kothari R, Malla AP, Tokhunts R, Lin A , Ji M, Xu R, Saavedra H, Snowman AM, Ricco C, Albacarys LK , Sbodio JI, Sedlak TW, Paul BD* and Snyder SH. Bilirubin links heme catabolism to neuroprotection by scavenging superoxide radicals. Cell Chem Biol. 2019; 26(10):1450-1460 (*Corresponding). PMID: 31353321. More Than Just Jaundice: Mouse Study Shows Bilirubin May Protect The Brain (hopkinsmedicine.org)
Zivanovic J, Kouroussis E, Kohl J, Adhikari B, Schot-Roux S, Thomas D, Miljkovic J, Bursac B, Petrovic D, Jung Y, Miler M, Mitchell SJ, Milosevic V, Gomes EJ, Benhar M, Gonzales-Zorn B, Ivanovic-Burmazovic I, Torregrossa R, Mitchell JR, Whiteman M, Schwarz G, Snyder SH, Paul BD, Carroll KS, Filipovic MR. Selective persulfide detection reveals evolutionarily conserved anti-aging effects of s-sulfhydration. Cell Metab. 2019; 30(6):1152-1170. PMID: 31735592.
Sedlak TW#, Paul BD#, Parker GM, Hester LD, Snowman AM, Taniguchi Y, Kamiya A, Snyder SH and Sawa A. The glutathione cycle shapes synaptic glutamate activity Proc Natl Acad Sci USA. 2019; 116(7):2701-2706. (#Co-first author). PMID: 30692251.
Sbodio JI#, Snyder SH* and Paul BD#*. Golgi stress response reprograms cysteine metabolism to confer cytoprotection in Huntington’s disease. Proc Natl Acad Sci USA. 2018; 115(4):780-785. PMID: 29317536. (#Equal contribution, *Corresponding). [A New Signaling Pathway Involving the Golgi Apparatus Identified in Cells With Huntington’s Disease (hopkinsmedicine.org)
Sbodio JI#, Snyder SH* and Paul BD#*. Transcriptional control of amino acid homeostasis is disrupted in Huntington’s disease. Proc Natl Acad Sci USA. 2016; 113(31):8843-8848. PMID: 27436896. (#Equal contribution, *Corresponding). New Evidence: How Amino Acid Cysteine Combats Huntington’s Disease – 07/26/2016 (hopkinsmedicine.org)
Sbodio JI, Paul BD, Machamer C and Snyder SH. Golgi protein ACBD3 mediates neurotoxicity associated with Huntington’s Disease. Cell Rep. 2013; 4(5):890-897. PMID: 24012756.
Paul BD, Sbodio JI, Xu R, Vandiver MS, Cha JY, Snowman AM and Snyder SH. Cystathionine g-lyase deficiency mediates neurodegeneration in Huntington’s disease. Nature. 2014; 509(7498):96-100. PMID: 24670645. Brain Degeneration In Huntington’s Disease Caused By Amino Acid Deficiency – 03/26/2014 (hopkinsmedicine.org)
Paul BD and Snyder SH. H₂S signaling through protein sulfhydration and beyond. Nat Rev Mol Cell Biol. 2012; 13(8):499-507. PMID: 22781905. (COVER PAGE ARTICLE).