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.

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


Professor
Boston University School of Medicine
Neurology



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


Targeting Stress Granule Biology in Alzheimer's Disease
07/01/2015 - 06/30/2018 (PI)
Bright Focus Foundation

RNA binding proteins as novel targets in Alzheimer's disease
09/15/2015 - 04/30/2018 (PI)
NIH/National Institute on Aging
5R01AG050471-02

Targeting RNA Metabolism and the Stress Granule Pathway to Inhibit Tau Aggregation
12/31/2015 - 12/30/2017 (PI)
The Edward N. & Della L. Thome Memorial

The Role of Acetylation in regulating pathophysiology of tau
09/01/2014 - 08/31/2017 (PI)
Mayo Clinic NIH NINDS
5R01NS089544-03

It Takes TIA to Tangle: The Role of RNA Binding Proteins in AD
01/01/2014 - 06/30/2017 (PI)
Alzheimer's Association

Regulation of RNA translation by MAPT in Alzheimer's disease
09/01/2015 - 02/28/2017 (PI)
Cure Alzheimer's Fund

Stress Granules and the Biology of TDP-43
01/01/2016 - 12/31/2016 (PI)
NIH/National Institute of Environmental
4R01ES020395-05

TDP-43 aggregation for the treatment of ALS
09/15/2015 - 09/14/2016 (PI)
Aquinnah Pharmaceuticals, Inc. NIH NINDS
1R43NS095481-01

Target Identification for TDP-43 Inclusion Inhibitors
03/01/2014 - 03/01/2016 (PI)
Massachusetts Life Sciences Center

Stress Granules and the Biology of TDP-43
03/01/2012 - 12/31/2015 (PI)
NIH/National Institute of Environmental
5R01ES020395-04

Showing 10 of 27 results. Show All Results



Yr Title Project-Sub Proj Pubs
2017 RNA binding proteins as novel targets in Alzheimer's disease 3R01AG050471-03S1 2
2017 The role of acetylation in regulating pathophysiology of tau 5R01NS089544-04 4
2016 RNA binding proteins as novel targets in Alzheimer's disease 5R01AG050471-02 2
2016 TDP-43 aggregation inhibitors for the treatment of ALS 5R43NS095481-02
2016 The role of acetylation in regulating pathophysiology of tau 5R01NS089544-03 4
2016 Stress Granules and the Biology of TDP-43 4R01ES020395-05 37
2015 RNA binding proteins as novel targets in Alzheimer's disease 1R01AG050471-01 2
2015 TDP-43 aggregation inhibitors for the treatment of ALS 1R43NS095481-01
2015 The role of acetylation in regulating pathophysiology of tau 5R01NS089544-02 4
2015 Stress Granules and the Biology of TDP-43 5R01ES020395-04 37
Showing 10 of 40 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.

  1. Wolozin B, Sotiropoulos I. Dendritic TAU-telidge. EBioMedicine. 2017 Jun; 20:3-4. PMID: 28529034.
  2. Ash PEA, Stanford EA, Al Abdulatif A, Ramirez-Cardenas A, Ballance HI, Boudeau S, Jeh A, Murithi JM, Tripodis Y, Murphy GJ, Sherr DH, Wolozin B. Dioxins and related environmental contaminants increase TDP-43 levels. Mol Neurodegener. 2017 May 05; 12(1):35.View Related Profiles. PMID: 28476168; DOI: 10.1186/s13024-017-0177-9;.
  3. Russo A, Scardigli R, La Regina F, Murray ME, Romano N, Dickson DW, Wolozin B, Cattaneo A, Ceci M. Increased cytoplasmic TDP-43 reduces global protein synthesis by interacting with RACK1 on polyribosomes. Hum Mol Genet. 2017 Apr 15; 26(8):1407-1418. PMID: 28158562; DOI: 10.1093/hmg/ddx035;.
  4. Maziuk B, Ballance HI, Wolozin B. Dysregulation of RNA Binding Protein Aggregation in Neurodegenerative Disorders. Front Mol Neurosci. 2017; 10:89. PMID: 28420962; DOI: 10.3389/fnmol.2017.00089;.
  5. Zhu H, Xue X, Wang E, Wallack M, Na H, Hooker JM, Kowall N, Tao Q, Stein TD, Wolozin B, Qiu WQ. Amylin receptor ligands reduce the pathological cascade of Alzheimer''s disease. Neuropharmacology. 2017 Jun; 119:170-181.View Related Profiles. PMID: 28363773; DOI: 10.1016/j.neuropharm.2017.03.030;.
  6. Sindi S, Ngandu T, Hovatta I, Kåreholt I, Antikainen R, Hänninen T, Levälahti E, Laatikainen T, Lindström J, Paajanen T, Peltonen M, Khalsa DS, Wolozin B, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M, Solomon A. Baseline Telomere Length and Effects of a Multidomain Lifestyle Intervention on Cognition: The FINGER Randomized Controlled Trial. J Alzheimers Dis. 2017; 59(4):1459-1470. PMID: 28777749.
  7. Kuwahara T, Inoue K, D''Agati VD, Fujimoto T, Eguchi T, Saha S, Wolozin B, Iwatsubo T, Abeliovich A. LRRK2 and RAB7L1 coordinately regulate axonal morphology and lysosome integrity in diverse cellular contexts. Sci Rep. 2016 Jul 18; 6:29945. PMID: 27424887; PMCID: PMC4947924; DOI: 10.1038/srep29945;.
  8. Wolozin B, Ikezu T. Corrigendum to "Syk and ye shall find" [EBioMedicine 2 (11) (2015) 190-1591]. EBioMedicine. 2016 Jun; 8:349.View Related Profiles. PMID: 27428444; DOI: 10.1016/j.ebiom.2016.05.033;.
  9. Vanderweyde T, Apicco DJ, Youmans-Kidder K, Ash PEA, Cook C, Lummertz da Rocha E, Jansen-West K, Frame AA, Citro A, Leszyk JD, Ivanov P, Abisambra JF, Steffen M, Li H, Petrucelli L, Wolozin B. Interaction of tau with the RNA-Binding Protein TIA1 Regulates tau Pathophysiology and Toxicity. Cell Rep. 2016 May 17; 15(7):1455-1466.View Related Profiles. PMID: 27160897; DOI: 10.1016/j.celrep.2016.04.045;.
  10. Meier S, Bell M, Lyons DN, Rodriguez-Rivera J, Ingram A, Fontaine SN, Mechas E, Chen J, Wolozin B, LeVine H, Zhu H, Abisambra JF. Pathological Tau Promotes Neuronal Damage by Impairing Ribosomal Function and Decreasing Protein Synthesis. J Neurosci. 2016 Jan 20; 36(3):1001-7. PMID: 26791227; PMCID: PMC4719006; DOI: 10.1523/JNEUROSCI.3029-15.2016;.
Showing 10 of 164 results. Show More

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

Bar chart showing 164 publications over 34 distinct years, with a maximum of 10 publications in 1996 and 2001 and 2004 and 2012

YearPublications
19801
19811
19822
19861
19874
19882
19901
19911
19926
19937
19943
19954
199610
19974
19985
19994
20006
200110
20026
20035
200410
20053
20068
20073
20083
20093
20108
20117
201210
20135
20146
20154
20165
20176

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