Molecular Medicine

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* (Molecular Medicine Faculty Profile)

Laura J. Blair

Laura J. Blair, PhD

Associate Professor, Molecular Medicine

Contact Info

Education

  • PhD, Medical Sciences, University of South Florida, 2014
  • MS, Medical Sciences, University of South Florida, 2013
  • BA, Chemistry, USF, 2009

Interdisciplinary and Emerging Signature Programs

  • Neuroscience

Research Interests

  • In your cells there are a group of sentinel proteins called chaperones that ensure the well-being of the other cellular proteins and functions. Our lab is focused on the role of chaperones in a group of more than 15 neurological degenerative diseases collectively termed “tauopathies”, the most common being Alzheimer's disease. We hope that an understanding of chaperone function will enable therapeutic strategies that increase quality of life, halt disease progression and ultimately cure neurodegenerative diseases.

Memberships

  • Member (ISTAART, 2017 - Present)
  • Memeber (Society for Neuroscience, 2014 - Present)
  • Student Member (Society for Neuroscience, 2009 - 2014)

Recent Publications

  • Oroz J, Chang BJ, Wysoczanski P, Lee CT, Pérez-Lara Á, Chakraborty P, Hofele RV, Baker JD, Blair LJ, Biernat J, Urlaub H, Mandelkow E, Dickey CA, Zweckstetter M. Structure and pro-toxic mechanism of the human Hsp90/PPIase/Tau complex. Nature communications. 9(1) : 4532, 2018.
  • Sabbagh JJ, Cordova RA, Zheng D, Criado-Marrero M, Lemus A, Li P, Baker JD, Nordhues BA, Darling AL, Martinez-Licha C, Rutz DA, Patel S, Buchner J, Leahy JW, Koren J, Dickey CA, Blair LJ. Targeting the FKBP51/GR/Hsp90 Complex to Identify Functionally Relevant Treatments for Depression and PTSD. ACS chemical biology. 13(8) : 2288-2299, 2018.
  • Baker JD, Ozsan I, Rodriguez Ospina S, Gulick D, Blair LJ. Hsp90 Heterocomplexes Regulate Steroid Hormone Receptors: From Stress Response to Psychiatric Disease. International journal of molecular sciences. 20(1) , 2018.
  • Stothert AR, Suntharalingam A, Tang X, Crowley VM, Mishra SJ, Webster JM, Nordhues BA, Huard DJE, Passaglia CL, Lieberman RL, Blagg BSJ, Blair LJ, Koren J, Dickey CA. Isoform-selective Hsp90 inhibition rescues model of hereditary open-angle glaucoma. Scientific reports. 7(1) : 17951, 2017.
  • Shelton LB, Koren J, Blair LJ. Imbalances in the Hsp90 Chaperone Machinery: Implications for Tauopathies. Frontiers in neuroscience. 11: 724, 2017.
  • Baker JD, Shelton LB, Zheng D, Favretto F, Nordhues BA, Darling A, Sullivan LE, Sun Z, Solanki PK, Martin MD, Suntharalingam A, Sabbagh JJ, Becker S, Mandelkow E, Uversky VN, Zweckstetter M, Dickey CA, Koren J, Blair LJ. Human cyclophilin 40 unravels neurotoxic amyloids. PLoS biology. 15(6) : e2001336, 2017.
  • Shelton LB, Baker JD, Zheng D, Sullivan LE, Solanki PK, Webster JM, Sun Z, Sabbagh JJ, Nordhues BA, Koren J, Ghosh S, Blagg BSJ, Blair LJ, Dickey CA. Hsp90 activator Aha1 drives production of pathological tau aggregates. Proceedings of the National Academy of Sciences of the United States of America. 114(36) : 9707-9712, 2017.
  • Fontaine SN, Zheng D, Sabbagh JJ, Martin MD, Chaput D, Darling A, Trotter JH, Stothert AR, Nordhues BA, Lussier A, Baker J, Shelton L, Kahn M, Blair LJ, Stevens SM, Dickey CA. DnaJ/Hsc70 chaperone complexes control the extracellular release of neurodegenerative-associated proteins. The EMBO journal. 35(14) : 1537-49, 2016.
  • Zheng D, Sabbagh JJ, Blair LJ, Darling AL, Wen X, Dickey CA. MicroRNA-511 Binds to FKBP5 mRNA, Which Encodes a Chaperone Protein, and Regulates Neuronal Differentiation. The Journal of biological chemistry. 291(34) : 17897-906, 2016.
  • Sabbagh JJ, Fontaine SN, Shelton LB, Blair LJ, Hunt JB, Zhang B, Gutmann JM, Lee DC, Lloyd JD, Dickey CA. Noncontact Rotational Head Injury Produces Transient Cognitive Deficits but Lasting Neuropathological Changes. Journal of neurotrauma. 33(19) : 1751-1760, 2016.
  • Blair LJ, Frauen HD, Zhang B, Nordhues BA, Bijan S, Lin YC, Zamudio F, Hernandez LD, Sabbagh JJ, Selenica ML, Dickey CA. Tau depletion prevents progressive blood-brain barrier damage in a mouse model of tauopathy. Acta neuropathologica communications. 3: 8, 2015.
  • Blair LJ, Baker JD, Sabbagh JJ, Dickey CA. The emerging role of peptidyl-prolyl isomerase chaperones in tau oligomerization, amyloid processing, and Alzheimer''s disease. Journal of neurochemistry. 133(1) : 1-13, 2015.
  • Blair LJ, Sabbagh JJ, Dickey CA. Targeting Hsp90 and its co-chaperones to treat Alzheimer''s disease. Expert opinion on therapeutic targets. 18(10) : 1219-32, 2014.
  • Selenica ML, Davtyan H, Housley SB, Blair LJ, Gillies A, Nordhues BA, Zhang B, Liu J, Gestwicki JE, Lee DC, Gordon MN, Morgan D, Dickey CA. Epitope analysis following active immunization with tau proteins reveals immunogens implicated in tau pathogenesis. Journal of neuroinflammation. 11: 152, 2014.
  • Sabbagh JJ, O''Leary JC, Blair LJ, Klengel T, Nordhues BA, Fontaine SN, Binder EB, Dickey CA. Age-associated epigenetic upregulation of the FKBP5 gene selectively impairs stress resiliency. PloS one. 9(9) : e107241, 2014.
  • Abisambra JF Jinwal UK Miyata Y Rogers J Blair L Li X Seguin SP Wang L Jin Y Bacon J et al. Allosteric heat shock protein 70 inhibitors rapidly rescue synaptic plasticity deficits by reducing aberrant tau. Biol Psychiatry. 74: 367-374., 2013.
  • O''Leary JC 3rd B, Zhang Koren J III Blair LJ Dickey CA. The Role of FKBP5 in Mood Disorders: Action of FKBP5 on Steroid Hormone Receptors Leads to Questions About its Evolutionary Importance. CNS Neurol Disord Drug Targets.. 12(8) : 1157-62, 2013.
  • Abisambra JF, Jinwal UK, Blair LJ, O''Leary JC, Li Q, Brady S, Wang L, Guidi CE, Zhang B, Nordhues BA, Cockman M, Suntharalingham A, Li P, Jin Y, Atkins CA, Dickey CA. Tau accumulation activates the unfolded protein response by impairing endoplasmic reticulum-associated degradation. The Journal of neuroscience : the official journal of the Society for Neuroscience. 33(22) : 9498-507, 2013.
  • Jinwal UK, Akoury E, Abisambra JF, O''Leary JC, Thompson AD, Blair LJ, Jin Y, Bacon J, Nordhues BA, Cockman M, Zhang J, Li P, Zhang B, Borysov S, Uversky VN, Biernat J, Mandelkow E, Gestwicki JE, Zweckstetter M, Dickey CA. Imbalance of Hsp70 family variants fosters tau accumulation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 27(4) : 1450-9, 2013.
  • Blair LJ, Zhang B, Dickey CA. Potential synergy between tau aggregation inhibitors and tau chaperone modulators. Alzheimer''s research & therapy. 5(5) : 41, 2013.
  • Blair LJ, Nordhues BA, Hill SE, Scaglione KM, O''Leary JC, Fontaine SN, Breydo L, Zhang B, Li P, Wang L, Cotman C, Paulson HL, Muschol M, Uversky VN, Klengel T, Binder EB, Kayed R, Golde TE, Berchtold N, Dickey CA. Accelerated neurodegeneration through chaperone-mediated oligomerization of tau. The Journal of clinical investigation. 123(10) : 4158-69, 2013.
  • Suntharalingam A O''Leary JC III Koren J III Joe MK Blair LJ Hill SE Abisambra JF Jinwal UK Cockman M Duerfeldt AS Rapoport T Ye Y Tomarev S Blagg BSJ Lieberman RL and Dickey CA. Grp94 depletion shunts mutant myocilin away from ERAD towards a more efficient clearance mechanism. Journal of Biological Chemistry.. 287(48) : 40661-40669., 2012.
  • Suntharalingam A, Abisambra JF, O''Leary JC, Koren J, Zhang B, Joe MK, Blair LJ, Hill SE, Jinwal UK, Cockman M, Duerfeldt AS, Tomarev S, Blagg BS, Lieberman RL, Dickey CA. Glucose-regulated protein 94 triage of mutant myocilin through endoplasmic reticulum-associated degradation subverts a more efficient autophagic clearance mechanism. The Journal of biological chemistry. 287(48) : 40661-9, 2012.
  • Koren J, Miyata Y, Kiray J, O''Leary JC, Nguyen L, Guo J, Blair LJ, Li X, Jinwal UK, Cheng JQ, Gestwicki JE, Dickey CA. Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance. PloS one. 7(4) : e35566, 2012.
  • O''Leary JC, Dharia S, Blair LJ, Brady S, Johnson AG, Peters M, Cheung-Flynn J, Cox MB, de Erausquin G, Weeber EJ, Jinwal UK, Dickey CA. A new anti-depressive strategy for the elderly: ablation of FKBP5/FKBP51. PloS one. 6(9) : e24840, 2011.
  • Jones JR, Lebar MD, Jinwal UK, Abisambra JF, Koren J, Blair L, O''Leary JC, Davey Z, Trotter J, Johnson AG, Weeber E, Eckman CB, Baker BJ, Dickey CA. The diarylheptanoid (+)-aR,11S-myricanol and two flavones from bayberry (Myrica cerifera) destabilize the microtubule-associated protein tau. Journal of natural products. 74(1) : 38-44, 2011.
  • Abisambra JF, Jinwal UK, Jones JR, Blair LJ, Koren J, Dickey CA. Exploiting the diversity of the heat-shock protein family for primary and secondary tauopathy therapeutics. Current neuropharmacology. 9(4) : 623-31, 2011.
  • Koren J, Jinwal UK, Jin Y, O''Leary J, Jones JR, Johnson AG, Blair LJ, Abisambra JF, Chang L, Miyata Y, Cheng AM, Guo J, Cheng JQ, Gestwicki JE, Dickey CA. Facilitating Akt clearance via manipulation of Hsp70 activity and levels. The Journal of biological chemistry. 285(4) : 2498-505, 2010.
  • Jinwal UK, O''Leary JC, Borysov SI, Jones JR, Li Q, Koren J, Abisambra JF, Vestal GD, Lawson LY, Johnson AG, Blair LJ, Jin Y, Miyata Y, Gestwicki JE, Dickey CA. Hsc70 rapidly engages tau after microtubule destabilization. The Journal of biological chemistry. 285(22) : 16798-805, 2010.
  • O''Leary JC, Li Q, Marinec P, Blair LJ, Congdon EE, Johnson AG, Jinwal UK, Koren J, Jones JR, Kraft C, Peters M, Abisambra JF, Duff KE, Weeber EJ, Gestwicki JE, Dickey CA. Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden. Molecular neurodegeneration. 5: 45, 2010.
  • Abisambra JF, Blair LJ, Hill SE, Jones JR, Kraft C, Rogers J, Koren J, Jinwal UK, Lawson L, Johnson AG, Wilcock D, O''Leary JC, Jansen-West K, Muschol M, Golde TE, Weeber EJ, Banko J, Dickey CA. Phosphorylation dynamics regulate Hsp27-mediated rescue of neuronal plasticity deficits in tau transgenic mice. The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(46) : 15374-82, 2010.
  • Jinwal UK, Koren J, Borysov SI, Schmid AB, Abisambra JF, Blair LJ, Johnson AG, Jones JR, Shults CL, O''Leary JC, Jin Y, Buchner J, Cox MB, Dickey CA. The Hsp90 cochaperone, FKBP51, increases Tau stability and polymerizes microtubules. The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(2) : 591-9, 2010.
  • Lee DC, Rizer J, Selenica ML, Reid P, Kraft C, Johnson A, Blair L, Gordon MN, Dickey CA, Morgan D. LPS- induced inflammation exacerbates phospho-tau pathology in rTg4510 mice. Journal of neuroinflammation. 7: 56, 2010.
  • Koren J, Jinwal UK, Lee DC, Jones JR, Shults CL, Johnson AG, Anderson LJ, Dickey CA. Chaperone signalling complexes in Alzheimer''s disease. Journal of cellular and molecular medicine. 13(4) : 619-30, 2009.
  • Dickey C, Kraft C, Jinwal U, Koren J, Johnson A, Anderson L, Lebson L, Lee D, Dickson D, de Silva R, Binder LI, Morgan D, Lewis J. Aging analysis reveals slowed tau turnover and enhanced stress response in a mouse model of tauopathy. The American journal of pathology. 174(1) : 228-38, 2009.
  • Jiang L, Chakraborty P, Zhang L, Wong M, Hill SE, Webber CJ, Libera J, Blair LJ, Wolozin B, Zweckstetter MA. Chaperoning of specific tau structure by immunophilin FKBP12 regulates the neuronal resilience to extracellular stress Science Advances. 9(5) , 2023.
  • Gebru NT, Hill SE, Blair LJ Genetically Engineered Mouse Models of FK506-Binding Protein 5 Journal of Cellular Biochemistry. , 2023.
  • Hill SE, Beaulieu-Abdelahad D, Lemus A, Webster JM, Rodriguez Ospina S, Darling AL, Martin MD, Patel S, Bridenstine L, Swonger R, Paul S, Blackburn R, Calcul L, Dickey CA, Leahy JW, and Blair LJ Benzothiazole Substitution Analogs of Rhodacyanine Hsp70 Inhibitors Modulate Tau Accumulation ACS Chemical Biology. 18: 1124-1135, 2023.
  • Esquivel AR, Hill SE, Blair LJ DnaJs are enriched in tau regulators International Journal of Biological Macromolecules. 253(7) : 127486, 2023.
  • Hill SE, Esquivel AR, Ospina SR, Rahal LM, Dickey CA, Blair LJ. Chaperoning activity of the cyclophilin family prevents tau aggregation. Protein science : a publication of the Protein Society. 31(11) : e4448, 2022.
  • Rodriguez Ospina S, Blazier DM, Criado-Marrero M, Gould LA, Gebru NT, Beaulieu-Abdelahad D, Wang X, Remily-Wood E, Chaput D, Stevens S, Uversky VN, Bickford PC, Dickey CA, Blair LJ. Small Heat Shock Protein 22 Improves Cognition and Learning in the Tauopathic Brain. International journal of molecular sciences. 23(2) , 2022.
  • Green R, Mayilsamy K, McGill AR, Martinez TE, Chandran B, Blair LJ, Bickford PC, Mohapatra SS, Mohapatra S. SARS-CoV-2 infection increases the gene expression profile for Alzheimer''s disease risk. Molecular therapy. Methods & clinical development. 27: 217-229, 2022.
  • Criado-Marrero M, Blazier DM, Gould LA, Gebru NT, Rodriguez Ospina S, Armendariz DS, Darling AL, Beaulieu-Abdelahad D, Blair LJ. Evidence against a contribution of the CCAAT-enhancer binding protein homologous protein (CHOP) in mediating neurotoxicity in rTg4510 mice. Scientific reports. 12(1) : 7372, 2022.
  • Sandusky-Beltran LA, Kovalenko A, Placides DS, Ratnasamy K, Ma C, Hunt JB, Liang H, Calahatian JIT, Michalski C, Fahnestock M, Blair LJ, Darling AL, Baker JD, Fontaine SN, Dickey CA, Gamsby JJ, Nash KR, Abner E, Selenica MB, Lee DC. Aberrant AZIN2 and polyamine metabolism precipitates tau neuropathology. The Journal of clinical investigation. 131(4) , 2021.
  • Criado-Marrero M, Gebru NT, Blazier DM, Gould LA, Baker JD, Beaulieu-Abdelahad D, Blair LJ. Correction to: Hsp90 co‑chaperones, FKBP52 and Aha1, promote tau pathogenesis in aged wild‑type mice. Acta neuropathologica communications. 9(1) : 85, 2021.
  • Criado-Marrero M, Gebru NT, Gould LA, Blazier DM, Vidal-Aguiar Y, Smith TM, Abdelmaboud SS, Shelton LB, Wang X, Dahrendorff J, Beaulieu-Abdelahad D, Dickey CA, Blair LJ. FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model. NPJ aging and mechanisms of disease. 7(1) : 9, 2021.
  • Criado-Marrero M, Gebru NT, Blazier DM, Gould LA, Baker JD, Beaulieu-Abdelahad D, Blair LJ. Hsp90 co-chaperones, FKBP52 and Aha1, promote tau pathogenesis in aged wild-type mice. Acta neuropathologica communications. 9(1) : 65, 2021.
  • Darling AL, Dahrendorff J, Creodore SG, Dickey CA, Blair LJ, Uversky VN. Small heat shock protein 22 kDa can modulate the aggregation and liquid-liquid phase separation behavior of tau. Protein science : a publication of the Protein Society. 30(7) : 1350-1359, 2021.
  • Favretto F, Baker JD, Strohäker T, Andreas LB, Blair LJ, Becker S, Zweckstetter M. The Molecular Basis of the Interaction of Cyclophilin A with α-Synuclein. Angewandte Chemie (International ed. in English). 59(14) : 5643-5646, 2020.
  • Criado-Marrero M, Smith TM, Gould LA, Kim S, Penny HJ, Sun Z, Gulick D, Dickey CA, Blair LJ. FKBP5 and early life stress affect the hippocampus by an age-dependent mechanism. Brain, behavior, & immunity - health. 9: 100143, 2020.
  • Criado-Marrero M, Sabbagh JJ, Jones MR, Chaput D, Dickey CA, Blair LJ. Hippocampal Neurogenesis Is Enhanced in Adult Tau Deficient Mice. Cells. 9(1) , 2020.
  • Favretto F, Flores D, Baker JD, Strohäker T, Andreas LB, Blair LJ, Becker S, Zweckstetter M. Catalysis of proline isomerization and molecular chaperone activity in a tug-of-war. Nature communications. 11(1) : 6046, 2020.
  • Webster JM, Darling AL, Sanders TA, Blazier DM, Vidal-Aguiar Y, Beaulieu-Abdelahad D, Plemmons DG, Hill SE, Uversky VN, Bickford PC, Dickey CA, Blair LJ. Hsp22 with an N-Terminal Domain Truncation Mediates a Reduction in Tau Protein Levels. International journal of molecular sciences. 21(15) , 2020.
  • Singh JK, Hutt DM, Tait B, Guy NC, Sivils JC, Ortiz NR, Payan AN, Komaragiri SK, Owens JJ, Culbertson D, Blair LJ, Dickey C, Kuo SY, Finley D, Dyson HJ, Cox MB, Chaudhary J, Gestwicki JE, Balch WE. Management of Hsp90-Dependent Protein Folding by Small Molecules Targeting the Aha1 Co-Chaperone. Cell chemical biology. 27(3) : 292-305.e6, 2020.
  • Sandusky-Beltran LA, Kovalenko A, Ma C, Calahatian JIT, Placides DS, Watler MD, Hunt JB, Darling AL, Baker JD, Blair LJ, Martin MD, Fontaine SN, Dickey CA, Lussier AL, Weeber EJ, Selenica MB, Nash KR, Gordon MN, Morgan D, Lee DC. Spermidine/spermine-N-acetyltransferase ablation impacts tauopathy-induced polyamine stress response. Alzheimer''s research & therapy. 11(1) : 58, 2019.
  • Gracia L, Lora G, Blair LJ, Jinwal UK. Therapeutic Potential of the Hsp90/Cdc37 Interaction in Neurodegenerative Diseases. Frontiers in neuroscience. 13: 1263, 2019.
  • Oroz J, Blair LJ, Zweckstetter M. Dynamic Aha1 co-chaperone binding to human Hsp90. Protein science : a publication of the Protein Society. 28(9) : 1545-1551, 2019.
  • Webster JM, Darling AL, Uversky VN, Blair LJ. Small Heat Shock Proteins, Big Impact on Protein Aggregation in Neurodegenerative Disease. Frontiers in pharmacology. 10: 1047, 2019.
  • Criado-Marrero M, Gebru NT, Gould LA, Smith TM, Kim S, Blackburn RJ, Dickey CA, Blair LJ. Early Life Stress and High FKBP5 Interact to Increase Anxiety-Like Symptoms through Altered AKT Signaling in the Dorsal Hippocampus. International journal of molecular sciences. 20(11) , 2019.
  • Blair LJ, Genest O, Mollapour M. The multiple facets of the Hsp90 machine. Nature structural & molecular biology. 26(2) : 92-95, 2019.
  • Darling AL, Breydo L, Rivas EG, Gebru NT, Zheng D, Baker JD, Blair LJ, Dickey CA, Koren J, Uversky VN. Repeated repeat problems: Combinatorial effect of C9orf72-derived dipeptide repeat proteins. International journal of biological macromolecules. 127: 136-145, 2019.
  • Blair LJ, Criado-Marrero M, Zheng D, Wang X, Kamath S, Nordhues BA, Weeber EJ, Dickey CA. The Disease-Associated Chaperone FKBP51 Impairs Cognitive Function by Accelerating AMPA Receptor Recycling. eNeuro. 6(1) , 2019.
  • Criado-Marrero M, Rein T, Binder EB, Porter JT, Koren J, Blair LJ. Hsp90 and FKBP51: complex regulators of psychiatric diseases. Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 373(1738) , 2018.