Varghese John

Varghese John

Professor-in-Residence, Neurology, University of California Los Angeles

Interests

Drug Discovery for Alzheimer's disease and CNS disorders

Education and Training

University of MinnesotaPhD1985Medicinal Chemistry

Publications

  1. Videlock EJ, Hatami A, Zhu C, Kawaguchi R, Chen H, Khan T, Salem Yehya AH, Stiles L, Joshi S, Hoffman JM, Law KM, Rankin CR, Chang L, Maidment NT, John V, Geschwind DH, Pothoulakis C. Distinct Patterns of Gene Expression Changes in the Colon and Striatum of Young Mice Overexpressing Alpha-Synuclein Support Parkinson's Disease as a Multi-System Process.. Journal of Parkinson's disease, 2023.
  2. Barraza-Núñez N, Pérez-Núñez R, Gaete-Ramírez B, Barrios-Garrido A, Arriagada C, Poksay K, John V, Barnier JV, Cárdenas AM, Caviedes P. Pharmacological Inhibition of p-21 Activated Kinase (PAK) Restores Impaired Neurite Outgrowth and Remodeling in a Cellular Model of Down Syndrome.. Neurotoxicity research, 2023.
  3. Okawa H, Kondo T, Hokugo A, Cherian P, Sundberg O, Campagna JJ, Kashemirov BA, John V, Sun S, Ebetino FH, McKenna CE, Nishimura I. Fluorescent risedronate analogue 800CW-pRIS improves tooth extraction-associated abnormal wound healing in zoledronate-treated mice.. Communications medicine, 2022.
  4. Okawa H, Kondo T, Hokugo A, Cherian P, Campagna JJ, Lentini NA, Sung EC, Chiang S, Lin YL, Ebetino FH, John V, Sun S, McKenna CE, Nishimura I. Mechanism of bisphosphonate-related osteonecrosis of the jaw (BRONJ) revealed by targeted removal of legacy bisphosphonate from jawbone using competing inert hydroxymethylene diphosphonate.. eLife, 2022.
  5. Cohn W, Zhu C, Campagna J, Bilousova T, Spilman P, Teter B, Li F, Guo R, Elashoff D, Cole GM, Avidan A, Faull KF, Whitelegge J, Wong DTW, John V. Integrated Multiomics Analysis of Salivary Exosomes to Identify Biomarkers Associated with Changes in Mood States and Fatigue.. International journal of molecular sciences, 2022.
  6. Cohn W, Melnik M, Huang C, Teter B, Chandra S, Zhu C, McIntire LB, John V, Gylys KH, Bilousova T. Multi-Omics Analysis of Microglial Extracellular Vesicles From Human Alzheimer's Disease Brain Tissue Reveals Disease-Associated Signatures.. Frontiers in pharmacology, 2021.
  7. Miyoshi E, Bilousova T, Melnik M, Fakhrutdinov D, Poon WW, Vinters HV, Miller CA, Corrada M, Kawas C, Bohannan R, Caraway C, Elias C, Maina KN, Campagna JJ, John V, Gylys KH. Exosomal tau with seeding activity is released from Alzheimer's disease synapses, and seeding potential is associated with amyloid beta.. Laboratory investigation; a journal of technical methods and pathology, 2021.
  8. Zhu C, Bilousova T, Focht S, Jun M, Elias CJ, Melnik M, Chandra S, Campagna J, Cohn W, Hatami A, Spilman P, Gylys KH, John V. Correction to: Pharmacological inhibition of nSMase2 reduces brain exosome release and α-synuclein pathology in a Parkinson's disease model.. Molecular brain, 2021.
  9. Zhu C, Bilousova T, Focht S, Jun M, Elias CJ, Melnik M, Chandra S, Campagna J, Cohn W, Hatami A, Spilman P, Gylys KH, John V. Pharmacological inhibition of nSMase2 reduces brain exosome release and α-synuclein pathology in a Parkinson's disease model.. Molecular brain, 2021.
  10. Gabrielyan L, Liang H, Minalyan A, Hatami A, John V, Wang L. Behavioral Deficits and Brain α-Synuclein and Phosphorylated Serine-129 α-Synuclein in Male and Female Mice Overexpressing Human α-Synuclein.. Journal of Alzheimer's disease : JAD, 2021.
  11. Liu J, Campagna J, John V, Damoiseaux R, Mokhonova E, Becerra D, Meng H, McNally EM, Pyle AD, Kramerova I, Spencer MJ. A Small-Molecule Approach to Restore a Slow-Oxidative Phenotype and Defective CaMKIIβ Signaling in Limb Girdle Muscular Dystrophy.. Cell reports. Medicine, 2020.
  12. Shu C, Parfenova L, Mokhonova E, Collado JR, Damoiseaux R, Campagna J, John V, Crosbie RH. High-throughput screening identifies modulators of sarcospan that stabilize muscle cells and exhibit activity in the mouse model of Duchenne muscular dystrophy.. Skeletal muscle, 2020.
  13. Bilousova T, Simmons BJ, Knapp RR, Elias CJ, Campagna J, Melnik M, Chandra S, Focht S, Zhu C, Vadivel K, Jagodzinska B, Cohn W, Spilman P, Gylys KH, Garg NK, John V. Dual Neutral Sphingomyelinase-2/Acetylcholinesterase Inhibitors for the Treatment of Alzheimer's Disease.. ACS chemical biology, 2020.
  14. Heinzelman P, Powers DN, Wohlschlegel JA, John V. Shotgun Proteomic Profiling of Bloodborne Nanoscale Extracellular Vesicles.. Methods in molecular biology (Clifton, N.J.), 2019.
  15. Duong AT, Simmons BJ, Alam MP, Campagna J, Garg NK, John V. Synthesis of Fused Indolines by Interrupted Fischer Indolization in a Microfluidic Reactor.. Tetrahedron letters, 2018.
  16. Campagna J, Spilman P, Jagodzinska B, Bai D, Hatami A, Zhu C, Bilousova T, Jun M, Elias CJ, Pham J, Cole G, LaDu MJ, Jung ME, Bredesen DE, John V. A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model.. Scientific reports, 2018.
  17. Campagna J, Vadivel K, Jagodzinska B, Jun M, Bilousova T, Spilman P, John V. Evaluation of an Allosteric BACE Inhibitor Peptide to Identify Mimetics that Can Interact with the Loop F Region of the Enzyme and Prevent APP Cleavage.. Journal of molecular biology, 2018.
  18. Bilousova T, Elias C, Miyoshi E, Alam MP, Zhu C, Campagna J, Vadivel K, Jagodzinska B, Gylys KH, John V. Suppression of tau propagation using an inhibitor that targets the DK-switch of nSMase2.. Biochemical and biophysical research communications, 2018.
  19. Shkhyan R, Van Handel B, Bogdanov J, Lee S, Yu Y, Scheinberg M, Banks NW, Limfat S, Chernostrik A, Franciozi CE, Alam MP, John V, Wu L, Ferguson GB, Nsair A, Petrigliano FA, Vangsness CT, Vadivel K, Bajaj P, Wang L, Liu NQ, Evseenko D. Drug-induced modulation of gp130 signalling prevents articular cartilage degeneration and promotes repair.. Annals of the rheumatic diseases, 2018.
  20. Alam MP, Bilousova T, Spilman P, Vadivel K, Bai D, Elias CJ, Evseenko D, John V. A Small Molecule Mimetic of the Humanin Peptide as a Candidate for Modulating NMDA-Induced Neurotoxicity.. ACS chemical neuroscience, 2017.
  21. Subbiah N, Campagna J, Spilman P, Alam MP, Sharma S, Hokugo A, Nishimura I, John V. Deformable Nanovesicles Synthesized through an Adaptable Microfluidic Platform for Enhanced Localized Transdermal Drug Delivery.. Journal of drug delivery, 2017.
  22. Poksay KS, Sheffler DJ, Spilman P, Campagna J, Jagodzinska B, Descamps O, Gorostiza O, Matalis A, Mullenix M, Bredesen DE, Cosford ND, John V. Screening for Small Molecule Inhibitors of Statin-Induced APP C-terminal Toxic Fragment Production.. Frontiers in pharmacology, 2017.
  23. Alam MP, Jagodzinska B, Campagna J, Spilman P, John V. C-O bond Formation in a Microfluidic Reactor: High Yield SNAr Substitution of Heteroaryl Chlorides.. Tetrahedron letters, 2016.
  24. Heinzelman P, Bilousova T, Campagna J, John V. Nanoscale Extracellular Vesicle Analysis in Alzheimer's Disease Diagnosis and Therapy.. International journal of Alzheimer's disease, 2016.
  25. Spilman PR, Corset V, Gorostiza O, Poksay KS, Galvan V, Zhang J, Rao R, Peters-Libeu C, Vincelette J, McGeehan A, Dvorak-Ewell M, Beyer J, Campagna J, Bankiewicz K, Mehlen P, John V, Bredesen DE. Netrin-1 Interrupts Amyloid-β Amplification, Increases sAβPPα in vitro and in vivo, and Improves Cognition in a Mouse Model of Alzheimer's Disease.. Journal of Alzheimer's disease : JAD, 2016.
  26. Ellerby HM, Bredesen DE, Fujimura S, John V. Correction to hunter-killer peptide (HKP) for targeted therapy.. Journal of medicinal chemistry, 2015.
  27. Peters-Libeu C, Campagna J, Mitsumori M, Poksay KS, Spilman P, Sabogal A, Bredesen DE, John V. sAβPPα is a Potent Endogenous Inhibitor of BACE1.. Journal of Alzheimer's disease : JAD, 2015.
  28. Zhang Q, Descamps O, Hart MJ, Poksay KS, Spilman P, Kane DJ, Gorostiza O, John V, Bredesen DE. Paradoxical effect of TrkA inhibition in Alzheimer's disease models.. Journal of Alzheimer's disease : JAD, 2014.
  29. Spilman P, Descamps O, Gorostiza O, Peters-Libeu C, Poksay KS, Matalis A, Campagna J, Patent A, Rao R, John V, Bredesen DE. The multi-functional drug tropisetron binds APP and normalizes cognition in a murine Alzheimer's model.. Brain research, 2013.
  30. Theendakara V, Patent A, Peters Libeu CA, Philpot B, Flores S, Descamps O, Poksay KS, Zhang Q, Cailing G, Hart M, John V, Rao RV, Bredesen DE. Neuroprotective Sirtuin ratio reversed by ApoE4.. Proceedings of the National Academy of Sciences of the United States of America, 2013.
  31. Ng RA, Sun M, Bowers S, Hom RK, Probst GD, John V, Fang LY, Maillard M, Gailunas A, Brogley L, Neitz RJ, Tung JS, Pleiss MA, Konradi AW, Sham HL, Dappen MS, Adler M, Yao N, Zmolek W, Nakamura D, Quinn KP, Sauer JM, Bova MP, Ruslim L, Artis DR, Yednock TA. Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: prime side chromane-containing inhibitors.. Bioorganic & medicinal chemistry letters, 2013.
  32. Bredesen DE, John V. Next generation therapeutics for Alzheimer's disease.. EMBO molecular medicine, 2013.
  33. Descamps O, Spilman P, Zhang Q, Libeu CP, Poksay K, Gorostiza O, Campagna J, Jagodzinska B, Bredesen DE, John V. AβPP-selective BACE inhibitors (ASBI): novel class of therapeutic agents for alzheimer's disease.. Journal of Alzheimer's disease : JAD, 2013.
  34. Maccecchini ML, Chang MY, Pan C, John V, Zetterberg H, Greig NH. Posiphen as a candidate drug to lower CSF amyloid precursor protein, amyloid-β peptide and τ levels: target engagement, tolerability and pharmacokinetics in humans.. Journal of neurology, neurosurgery, and psychiatry, 2012.
  35. Libeu CA, Descamps O, Zhang Q, John V, Bredesen DE. Altering APP proteolysis: increasing sAPPalpha production by targeting dimerization of the APP ectodomain.. PloS one, 2012.
  36. Rao RV, Descamps O, John V, Bredesen DE. Ayurvedic medicinal plants for Alzheimer's disease: a review.. Alzheimer's research & therapy, 2012.
  37. Jin K, Mao XO, Xie L, John V, Greenberg DA. Pharmacological induction of neuroglobin expression.. Pharmacology, 2011.
  38. Descamps O, Zhang Q, John V, Bredesen DE. Induction of the C-terminal proteolytic cleavage of AβPP by statins.. Journal of Alzheimer's disease : JAD, 2011.
  39. Libeu CP, Poksay KS, John V, Bredesen DE. Structural and functional alterations in amyloid-β precursor protein induced by amyloid-β peptides.. Journal of Alzheimer's disease : JAD, 2011.
  40. Probst GD, Bowers S, Sealy JM, Stupi B, Dressen D, Jagodzinska BM, Aquino J, Gailunas A, Truong AP, Tso L, Xu YZ, Hom RK, John V, Tung JS, Pleiss MA, Tucker JA, Konradi AW, Sham HL, Jagodzinski J, Toth G, Brecht E, Yao N, Pan H, Lin M, Artis DR, Ruslim L, Bova MP, Sinha S, Yednock TA, Gauby S, Zmolek W, Quinn KP, Sauer JM. Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: structure-activity relationship of the aryl region.. Bioorganic & medicinal chemistry letters, 2010.
  41. Truong AP, Probst GD, Aquino J, Fang L, Brogley L, Sealy JM, Hom RK, Tucker JA, John V, Tung JS, Pleiss MA, Konradi AW, Sham HL, Dappen MS, Tóth G, Yao N, Brecht E, Pan H, Artis DR, Ruslim L, Bova MP, Sinha S, Yednock TA, Zmolek W, Quinn KP, Sauer JM. Improving the permeability of the hydroxyethylamine BACE-1 inhibitors: structure-activity relationship of P2' substituents.. Bioorganic & medicinal chemistry letters, 2010.
  42. Bredesen DE, John V, Galvan V. Importance of the caspase cleavage site in amyloid-β protein precursor.. Journal of Alzheimer's disease : JAD, 2010.
  43. Sealy JM, Truong AP, Tso L, Probst GD, Aquino J, Hom RK, Jagodzinska BM, Dressen D, Wone DW, Brogley L, John V, Tung JS, Pleiss MA, Tucker JA, Konradi AW, Dappen MS, Toth G, Pan H, Ruslim L, Miller J, Bova MP, Sinha S, Quinn KP, Sauer JM. Design and synthesis of cell potent BACE-1 inhibitors: structure-activity relationship of P1' substituents.. Bioorganic & medicinal chemistry letters, 2009.
  44. Ellerby HM, Bredesen DE, Fujimura S, John V. Hunter-killer peptide (HKP) for targeted therapy.. Journal of medicinal chemistry, 2008.
  45. Maillard MC, Hom RK, Benson TE, Moon JB, Mamo S, Bienkowski M, Tomasselli AG, Woods DD, Prince DB, Paddock DJ, Emmons TL, Tucker JA, Dappen MS, Brogley L, Thorsett ED, Jewett N, Sinha S, John V. Design, synthesis, and crystal structure of hydroxyethyl secondary amine-based peptidomimetic inhibitors of human beta-secretase.. Journal of medicinal chemistry, 2007.
  46. John V. Human beta-secretase (BACE) and BACE inhibitors: progress report.. Current topics in medicinal chemistry, 2006.
  47. Hom RK, Gailunas AF, Mamo S, Fang LY, Tung JS, Walker DE, Davis D, Thorsett ED, Jewett NE, Moon JB, John V. Design and synthesis of hydroxyethylene-based peptidomimetic inhibitors of human beta-secretase.. Journal of medicinal chemistry, 2004.
  48. John V, Beck JP, Bienkowski MJ, Sinha S, Heinrikson RL. Human beta-secretase (BACE) and BACE inhibitors.. Journal of medicinal chemistry, 2003.
  49. Hom RK, Fang LY, Mamo S, Tung JS, Guinn AC, Walker DE, Davis DL, Gailunas AF, Thorsett ED, Sinha S, Knops JE, Jewett NE, Anderson JP, John V. Design and synthesis of statine-based cell-permeable peptidomimetic inhibitors of human beta-secretase.. Journal of medicinal chemistry, 2003.
  50. Tung JS, Davis DL, Anderson JP, Walker DE, Mamo S, Jewett N, Hom RK, Sinha S, Thorsett ED, John V. Design of substrate-based inhibitors of human beta-secretase.. Journal of medicinal chemistry, 2002.