Benjamin Wolozin, MD, PhD
Professor
Boston University School of Medicine
Dept of Pharmacology & Experimental Therapeutics

MD, Albert Einstein College of Medicine




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.

Professor
Boston University School of Medicine
Neurology


Member
Boston University
Evans Center for Interdisciplinary Biomedical Research


Member
Boston University
Genome Science Institute


Graduate Faculty (Primary Mentor of Grad Students)
Boston University School of Medicine, Graduate Medical Sciences



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


Genetic Modifiers of Protein Interaction Networks in Tauopathy
08/01/2019 - 03/31/2024 (Multi-PI)
PI: Benjamin Wolozin, MD, PhD
NIH/National Institute on Aging
5R01AG064932-02

Systems-level functional proteomics analysis assemblies in Alzheimer's disease and mouse models of tauopathy
02/15/2019 - 01/31/2024 (Multi-PI)
PI: Benjamin Wolozin, MD, PhD
NIH/National Institute on Aging
1RF1AG061706-01

Capturing the molecular complexity of Alzheimer's disease through the lens of RNA binding proteins
06/01/2018 - 03/31/2023 (PI)
NIH/National Institute on Aging
3RF1AG056318-01A1S1

Development of synthetic gene feedback circuits to prevent tau aggregation
02/01/2020 - 01/31/2023 (PI)
Bright Focus Foundation


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

RNA binding proteins as novel targets in Alzheimer's disease
09/15/2015 - 04/30/2021 (PI)
NIH/National Institute on Aging
5R01AG050471-05

The Role of Acetylation in regulating pathophysiology of tau
09/01/2014 - 08/31/2019 (Subcontract PI)
Mayo Clinic NIH NINDS
5R01NS089544-05

Targeting Stress Granule Biology in Alzheimer's Disease
07/01/2015 - 06/30/2019 (PI)
Bright Focus Foundation


Transformative science driving new treatments for neurodegenerative diseases
02/07/2018 - 02/06/2019 (PI)
Pfizer, Inc.


INHIBITiON OF TAU PATHOLOGY IN HUMAN NEURONS
07/15/2017 - 07/14/2018 (PI)
Cure Alzheimer's Fund


Showing 10 of 34 results. Show All Results


Title


Yr Title Project-Sub Proj Pubs
2021 Genetic Modifiers of Protein Interaction Networks in Tauopathy 5R01AG064932-03 5
2020 Genetic Modifiers of Protein Interaction Networks in Tauopathy 5R01AG064932-02 5
2020 Genetic Modifiers of Protein Interaction Networks in Tauopathy 5R01AG064932-02 5
2020 Targeting tau for the development of novel Alzheimer's disease therapeutics 2R44AG060843-02
2020 Capturing the molecular complexity of Alzheimer's disease through the lens of RNA binding proteins 3RF1AG056318-01A1S1 8
2019 Genetic Modifiers of Protein Interaction Networks in Tauopathy 1R01AG064932-01 5
2019 Systems-level functional proteomics analysis assemblies in Alzheimer's disease and mouse models of tauopathy 1RF1AG061706-01 6
2019 Regulation of brain neuroprotection and inflammation by TIA1 5R21AG059925-02 5
2019 RNA binding proteins as novel targets in Alzheimer's disease 5R01AG050471-05 24
2019 TDP-43 aggregation inhibitors for the treatment of ALS 5R44NS095481-04
Showing 10 of 58 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. Ash PEA, Lei S, Shattuck J, Boudeau S, Carlomagno Y, Medalla M, Mashimo BL, Socorro G, Al-Mohanna LFA, Jiang L, Öztürk MM, Knobel M, Ivanov P, Petrucelli L, Wegmann S, Kanaan NM, Wolozin B. TIA1 potentiates tau phase separation and promotes generation of toxic oligomeric tau. Proc Natl Acad Sci U S A. 2021 Mar 02; 118(9).View Related Profiles. PMID: 33619090
     
  2. Sindi S, Solomon A, Kåreholt I, Hovatta I, Antikainen R, Hänninen T, Levälahti E, Laatikainen T, Lehtisalo J, Lindström J, Paajanen T, Peltonen M, Singh Khalsa D, Wolozin B, Strandberg T, Tuomilehto J, Soininen H, Ngandu T, Kivipelto M. Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline: A Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci. 2021 Feb 25; 76(3):491-498. PMID: 33175128
     
  3. Hekman RM, Hume AJ, Goel RK, Abo KM, Huang J, Blum BC, Werder RB, Suder EL, Paul I, Phanse S, Youssef A, Alysandratos KD, Padhorny D, Ojha S, Mora-Martin A, Kretov D, Ash PEA, Verma M, Zhao J, Patten JJ, Villacorta-Martin C, Bolzan D, Perea-Resa C, Bullitt E, Hinds A, Tilston-Lunel A, Varelas X, Farhangmehr S, Braunschweig U, Kwan JH, McComb M, Basu A, Saeed M, Perissi V, Burks EJ, Layne MD, Connor JH, Davey R, Cheng JX, Wolozin BL, Blencowe BJ, Wuchty S, Lyons SM, Kozakov D, Cifuentes D, Blower M, Kotton DN, Wilson AA, Mühlberger E, Emili A. Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2. Mol Cell. 2021 Jan 07; 81(1):212.View Related Profiles. PMID: 33417854
     
  4. Basu A, Ash PE, Wolozin B, Emili A. Protein Interaction Network Biology in Neuroscience. Proteomics. 2021 Feb; 21(3-4):e1900311.View Related Profiles. PMID: 33314619
     
  5. Hekman RM, Hume AJ, Goel RK, Abo KM, Huang J, Blum BC, Werder RB, Suder EL, Paul I, Phanse S, Youssef A, Alysandratos KD, Padhorny D, Ojha S, Mora-Martin A, Kretov D, Ash PEA, Verma M, Zhao J, Patten JJ, Villacorta-Martin C, Bolzan D, Perea-Resa C, Bullitt E, Hinds A, Tilston-Lunel A, Varelas X, Farhangmehr S, Braunschweig U, Kwan JH, McComb M, Basu A, Saeed M, Perissi V, Burks EJ, Layne MD, Connor JH, Davey R, Cheng JX, Wolozin BL, Blencowe BJ, Wuchty S, Lyons SM, Kozakov D, Cifuentes D, Blower M, Kotton DN, Wilson AA, Mühlberger E, Emili A. Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2. Mol Cell. 2020 12 17; 80(6):1104-1122.e9.View Related Profiles. PMID: 33259812; DOI: 10.1016/j.molcel.2020.11.028;
     
  6. Jiang L, Zhao J, Cheng JX, Wolozin B. Tau Oligomers and Fibrils Exhibit Differential Patterns of Seeding and Association With RNA Binding Proteins. Front Neurol. 2020; 11:579434.View Related Profiles. PMID: 33101187
     
  7. Pourhaghighi R, Ash PEA, Phanse S, Goebels F, Hu LZM, Chen S, Zhang Y, Wierbowski SD, Boudeau S, Moutaoufik MT, Malty RH, Malolepsza E, Tsafou K, Nathan A, Cromar G, Guo H, Al Abdullatif A, Apicco DJ, Becker LA, Gitler AD, Pulst SM, Youssef A, Hekman R, Havugimana PC, White CA, Blum BC, Ratti A, Bryant CD, Parkinson J, Lage K, Babu M, Yu H, Bader GD, Wolozin B, Emili A. BraInMap Elucidates the Macromolecular Connectivity Landscape of Mammalian Brain. Cell Syst. 2020 Aug 26; 11(2):208.View Related Profiles. PMID: 32853540
     
  8. Reiss AB, Glass AD, Wisniewski T, Wolozin B, Gomolin IH, Pinkhasov A, De Leon J, Stecker MM. Alzheimer's disease: many failed trials, so where do we go from here? J Investig Med. 2020 08; 68(6):1135-1140. PMID: 32699179
     
  9. Ruan QT, Yazdani N, Reed ER, Beierle JA, Peterson LP, Luttik KP, Szumlinski KK, Johnson WE, Ash PEA, Wolozin B, Bryant CD. 5' UTR variants in the quantitative trait gene Hnrnph1 support reduced 5' UTR usage and hnRNP H protein as a molecular mechanism underlying reduced methamphetamine sensitivity. FASEB J. 2020 07; 34(7):9223-9244.View Related Profiles. PMID: 32401417
     
  10. Webber CJ, Lei SE, Wolozin B. The pathophysiology of neurodegenerative disease: Disturbing the balance between phase separation and irreversible aggregation. Prog Mol Biol Transl Sci. 2020; 174:187-223. PMID: 32828466
     
Showing 10 of 198 results. Show More

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

Bar chart showing 198 publications over 38 distinct years, with a maximum of 11 publications in 2020

YearPublications
19801
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19822
19861
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19882
19901
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19954
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20026
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201210
20136
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20187
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202011
20213


Transient droplets organize biochemical reactions inside cells

Chemical & Engineering News 7/13/2020

Three BU Research Teams Win First Kilachand Fund Awards

BU Today 9/19/2019

Islands of Tau Coat and Protect Cytoskeleton

Alzforum 9/6/2019

Studies Point to DNA Difficulties in ALS/FTD

ALZFORUM 2/15/2019

To halt brain diseases, drugs take aim at protein traffic jams that kill neurons

Science 1/16/2019

Going the Distance: FUS Travels to Terminals, Drops Off RNA

Alzoforum 12/2/2018

How to Keep Stress Granules from Wreaking Havoc On Your Body

SHAPE 11/13/2018
In addition to these self-described keywords below, a list of MeSH based concepts is available here.

Alzheimer's disease
Amyotrophic lateral sclerosis
biochemistry
C. elegans
cell culture
confocal microscopy
gene knockdown
gene over-expression
hippocampal neurons (in culture)
immumohistochemistry
immunochemistry
immunocytochemistry
immunoprecipitation
induced pluripotent stem cells
live cell imaging
mouse models
movement disorders
Parkinson's disease
RNAi
transfection

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