Benjamin Wolozin, MD, PhD
Professor
Boston University Chobanian & Avedisian School of Medicine
Anatomy & Neurobiology

MD/PhD, Albert Einstein College of Medicine
BA, Wesleyan University



Dr. Wolozin’s research examines the pathophysiology of neurodegenerative diseases, including Alzheimer’s disease, Amyotrophic Lateral Sclerosis and Parkinson’s disease. His laboratory is currently focused on the role of RNA binding proteins and translational regulation in disease processes.

Parkinson’s disease: The research on Parkinson Disease focuses on genetic factors implicated in Parkinson’s disease, including LRRK2, a-synuclein, parkin, PINK1 and DJ-1. Research in our laboratory suggests that genetic mutations linked to Parkinson’s disease act by converging on a biological system that integrates the stress response, regulating autophagy, protein translation and mitochondrial function. Using genetically modified cells (e.g., primary neuronal cultures or cell lines) and genetically modified animals (C. elegans and mice), we have demonstrated that a-synuclein and LRRK2 enhance the sensitivity of dopaminergic neurons to mitochondrial dysfunction. Our work points to particular biochemical pathways mediating the actions of LRRK2. We have recently demonstrated that LRRK2 binds to MKK6, a kinase that lies upstream of p38 and regulates the stress response. LRRK2 regulates membrane localization of its binding proteins, including MKKs, JIPs, rac1 (a small GTPase) and other important proteins mediating the stress response. This work has direct relevance to therapy because it points to chemicals that might protect dopaminergic neurons and modify the course of Parkinson’s disease. For instance, we are investigating the action of SirT1 agonists (such resveratrol, the compound found in red wine or SRT1720, produced by Sirtris Pharmaceuticals), which stimulate synthesis of anti-oxidant enzymes and appear to offer protection in animal models of Parkinson’s disease. We are also investigating the action of brain penetrant analogues of rapamycin, which stimulate the neuron to remove protein aggregates, and offer neuroprotection through mechanisms complementary to SirT1.

Amyotrophic Lateral Sclerosis (ALS): Our current work focuses on a protein, TDP-43, that was recently shown to be the predominant protein that accumulates during the course of the disease. We have shown that TDP-43 is a stress granule protein, and that TDP-43 pathology co-localizes with other stress granule markers in spinal cords of subjects with ALS, as well as those with Frontotemporal Dementia. We are currently examining how TDP-43 and disease-linked mutations in TDP-43 modify synaptic function in neuronal arbors. We are using protein binding assays (immunoprecipitation, mass spectrometry) and imaging assay (fixed cells and live cell imaging) to determine the effects of TDP-43 and its mutations. We use cell lines, primary cultures of hippocampal neurons and human brain samples for our studies.

We also have an active drug discover program related to TDP-43. This program utilizes cells that inducibly over-express TDP-43, as well as lines of C. elegans expressing TDP-43 and studies in primary cultures of hippocampal neurons. We examine the compounds using imaging (in collaboration with Marcie Glicksman at LDDN) and biochemistry.

Alzheimer disease (AD): We have recently extended our work on stress granules to Alzheimer’s disease. As with ALS, we have shown that tau pathology (neurofibrillary tangles) in the AD brain co-localizes with stress granule markers. The amount of stress granule pathology in the AD brain is very striking. Proteins such as TIA-1, G3BP and TTP, strongly accumulate. Interestingly, though, the pattern of accumulation differs based on the stress granule protein. The pathology appears to correlate with binding to tau protein. TIA-1 and TTP both bind to tau, while G3BP does not bind tau. Stress granules might also directly modulate tau pathology, because co-transfecting TIA-1 with tau induces formation of phosphorylated tau inclusions. The work on AD and stress granules uses biochemical/immunochemical studies focusing on proteins implicated in AD (e.g., antibodies to tau) and on stress granule markers. The work also uses extensive imaging assays (fixed cells, live cell imaging, confocal microscopy). We use studies of hippocampal neurons grown culture, transgenic mice expressing P301L tau and human tissues.


The role of N6-methyladenosine modified RNA in Alzheimer's disease
12/15/2022 - 11/30/2027 (Multi-PI)
PI: Benjamin Wolozin, MD, PhD
NIH/National Institute on Aging
5R01AG080810-02

Circular RNAs and their interactions with RNA-binding proteins to modulate AD-related neuropathology
07/01/2021 - 06/30/2026 (Multi-PI)
PI: Benjamin Wolozin, MD, PhD
NIH/National Institute on Aging
5U01AG072577-04

Nanobodies targeting stress granule components
09/01/2023 - 08/31/2025 (Subcontract PI)
University of Connecticut NIH NIA
1R21AG083761-01

Genetic Modifiers of Protein Interaction Networks in Tauopathy
08/01/2019 - 03/31/2025 (Multi-PI)
PI: Benjamin Wolozin, MD, PhD
NIH/National Institute on Aging
5R01AG064932-05

TDP-43 aggregation for the treatment of ALS
09/15/2015 - 09/14/2024 (Multi-PI)
PI: Benjamin Wolozin, MD, PhD
Aquinnah Pharmaceuticals, Inc. NIH NINDS
1R43NS095481-01

Exploring the pathophysiology of AD and ADRDs with 3D Asteroid models
09/15/2021 - 08/31/2024 (PI)
NIH/National Institute on Aging
1R56AG074591-01

Systems-level functional proteomics analysis assemblies in Alzheimer's disease and mouse models of tauopathy
02/15/2019 - 06/30/2024 (Multi-PI)
PI: Benjamin Wolozin, MD, PhD
NIH/National Institute on Aging
1RF1AG061706-01

Development of synthetic gene feedback circuits to prevent tau aggregation
02/01/2020 - 01/31/2024 (Multi-PI)
PI: Benjamin Wolozin, MD, PhD
Bright Focus Foundation


Capturing the molecular complexity of Alzheimer's disease through the lens of RNA binding proteins
06/01/2018 - 08/31/2023 (PI)
NIH/National Institute on Aging
3RF1AG056318-01A1S1

Regulation of brain neuroprotection and inflammation by TIA1
08/15/2018 - 05/31/2021 (PI)
NIH/National Institute on Aging
5R21AG059925-02

Showing 10 of 39 results. Show All Results


Title


Yr Title Project-Sub Proj Pubs
2024 APOE Genotype Mediated Effects on Alzheimer Disease Risk and Mechanisms 1U01AG082665-01A1
2024 The role of N6-methyladenosine modified RNA in Alzheimer's disease 5R01AG080810-02
2024 Circular RNAs and their interactions with RNA-binding proteins to modulate AD-related neuropathology 5U01AG072577-04
2024 Circular RNAs and their interactions with RNA-binding proteins to modulate AD-related neuropathology 3U01AG072577-04S1
2024 Development of a novel Alzheimer's disease therapeutic targeting tau 2R44AG060843-04
2023 The role of N6-methyladenosine modified RNA in Alzheimer's disease 1R01AG080810-01
2023 The role of N6-methyladenosine modified RNA in Alzheimer's disease: Equipment Supplement 3R01AG080810-01S1
2023 Circular RNAs and their interactions with RNA-binding proteins to modulate AD-related neuropathology 5U01AG072577-03
2023 Genetic Modifiers of Protein Interaction Networks in Tauopathy 5R01AG064932-05
2022 Circular RNAs and their interactions with RNA-binding proteins to modulate AD-related neuropathology 5U01AG072577-02
Showing 10 of 71 results. Show All Results

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

iCite Analysis       Copy PMIDs To Clipboard

  1. Rondón-Ortiz AN, Zhang L, Ash PEA, Basu A, Puri S, van der Spek SJF, Wang Z, Dorrian L, Emili A, Wolozin B. Proximity labeling reveals dynamic changes in the SQSTM1 protein network. J Biol Chem. 2024 Sep; 300(9):107621.View Related Profiles. PMID: 39098523; PMCID: PMC11401034; DOI: 10.1016/j.jbc.2024.107621;
     
  2. Jiang L, Roberts R, Wong M, Zhang L, Webber CJ, Libera J, Wang Z, Kilci A, Jenkins M, Ortiz AR, Dorrian L, Sun J, Sun G, Rashad S, Kornbrek C, Daley SA, Dedon PC, Nguyen B, Xia W, Saito T, Saido TC, Wolozin B. ß-amyloid accumulation enhances microtubule associated protein tau pathology in an APPNL-G-F/MAPTP301S mouse model of Alzheimer's disease. Front Neurosci. 2024; 18:1372297. PMID: 38572146; PMCID: PMC10987964; DOI: 10.3389/fnins.2024.1372297;
     
  3. Rondón Ortiz AN, Zhang L, Ash PEA, Basu A, Puri S, van der Spek SJF, Dorrian L, Emili A, Wolozin B. Proximity labeling reveals dynamic changes in the SQSTM1 protein network. bioRxiv. 2023 Dec 13.View Related Profiles. PMID: 38168279; PMCID: PMC10760047; DOI: 10.1101/2023.12.12.571324;
     
  4. Webber CJ, Murphy CN, Rondón-Ortiz AN, van der Spek SJF, Kelly EX, Lampl NM, Chiesa G, Khalil AS, Emili A, Wolozin B. Human herpesvirus 8 ORF57 protein is able to reduce TDP-43 pathology: network analysis identifies interacting pathways. Hum Mol Genet. 2023 Oct 04; 32(20):2966-2980.View Related Profiles. PMID: 37522762; PMCID: PMC10549787; DOI: 10.1093/hmg/ddad122;
     
  5. Park J, Wu Y, Shao W, Gendron TF, van der Spek SJF, Sultanakhmetov G, Basu A, Castellanos Otero P, Jones CJ, Jansen-West K, Daughrity LM, Phanse S, Del Rosso G, Tong J, Castanedes-Casey M, Jiang L, Libera J, Oskarsson B, Dickson DW, Sanders DW, Brangwynne CP, Emili A, Wolozin B, Petrucelli L, Zhang YJ. Poly(GR) interacts with key stress granule factors promoting its assembly into cytoplasmic inclusions. Cell Rep. 2023 Aug 29; 42(8):112822.View Related Profiles. PMID: 37471224; PMCID: PMC10528326; DOI: 10.1016/j.celrep.2023.112822;
     
  6. Zhao J, Jiang L, Matlock A, Xu Y, Zhu J, Zhu H, Tian L, Wolozin B, Cheng JX. Mid-infrared chemical imaging of intracellular tau fibrils using fluorescence-guided computational photothermal microscopy. Light Sci Appl. 2023 Jun 15; 12(1):147. PMID: 37322011; PMCID: PMC10272128; DOI: 10.1038/s41377-023-01191-6;
     
  7. Jiang L, Roberts R, Wong M, Zhang L, Webber CJ, Kilci A, Jenkins M, Sun J, Sun G, Rashad S, Dedon PC, Daley SA, Xia W, Ortiz AR, Dorrian L, Saito T, Saido TC, Wolozin B. Accumulation of m6A exhibits stronger correlation with MAPT than ß-amyloid pathology in an APPNL-G-F /MAPTP301S mouse model of Alzheimer's disease. Res Sq. 2023 May 18. PMID: 37292629; PMCID: PMC10246280; DOI: 10.21203/rs.3.rs-2745852/v1;
     
  8. Jiang L, Roberts R, Wong M, Zhang L, Webber CJ, Kilci A, Jenkins M, Sun G, Rashad S, Sun J, Dedon PC, Daley SA, Xia W, Ortiz AR, Dorrian L, Saito T, Saido TC, Wolozin B. Accumulation of m 6 A exhibits stronger correlation with MAPT than ß-amyloid pathology in an APP NL-G-F /MAPT P301S mouse model of Alzheimer's disease. bioRxiv. 2023 Mar 28. PMID: 37034774; PMCID: PMC10081259; DOI: 10.1101/2023.03.28.534515;
     
  9. Zhao J, Jiang L, Matlock A, Xu Y, Zhu J, Zhu H, Tian L, Wolozin B, Cheng JX. Mid-infrared Chemical Imaging of Intracellular Tau Fibrils using Fluorescence-guided Computational Photothermal Microscopy. ArXiv. 2023 Feb 23. PMID: 36866226; PMCID: PMC9980272
     
  10. Puri S, Hu J, Sun Z, Lin M, Stein TD, Farrer LA, Wolozin B, Zhang X. Identification of circRNAs linked to Alzheimer's disease and related dementias. Alzheimers Dement. 2023 Aug; 19(8):3389-3405.View Related Profiles. PMID: 36795937; PMCID: PMC10427739; DOI: 10.1002/alz.12960;
     
Showing 10 of 214 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 214 publications over 41 distinct years, with a maximum of 11 publications in 2020

YearPublications
19801
19811
19822
19861
19874
19882
19901
19911
19926
19937
19943
19954
199610
19974
19985
19994
20006
200110
20026
20035
200410
20054
20068
20073
20083
20093
20108
20117
201210
20136
20146
20154
20167
20177
20187
20198
202011
20216
20222
20239
20242

2017 Boston University: Spivack Award: Distinguished Scholar in Neuroscience
2016 American Association for the Advancement of Science (AAAS): Fellow
2016 New Economy Magazine, World Media Group: Aquinnah Pharmaceuticals Inc., “Most innovative company in neurodegeneration research, 2016”
2013 Alzheimer Association: Zenith Award
2013 Boston University School of Medicine: Evans Center DOM Collaborator of the Year Award: Basic Sciences
2000 Loyola University Dept. of Pharmacology: Faculty of the Year
2000 Loyola University Medical Center: Graduate School Faculty of the Year
1993 Society for Biological Psychiatry: A. E. Bennett Award
1988 Society for Neuroscience: Donald B. Lindsley Prize

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