M.D., Ph.D., Albert Einstein College of Medicine
General field of research:
Affiliations other than medicine:
Evans Center for Interdisciplinary Biomedical Research
Pharmacology and Neurology
Phone: (617)-414 2652
Phone: (617)-414 2654
Fax: (617)-414 2651
Other research websites:
Parkinson’s disease; ALS; Alzheimer’s disease; Cell Culture; C. elegans; Protein aggregation; Neurodegeneration
Summary of research interest:
The research on Parkinson Disease focuses on genetic factors implicated in Parkinson’s disease, including LRRK2, α-synuclein, parkin, DJ-1 and, LRRK2. Research in our laboratory examines links between these genes and two cellular pathways, mitochondrial function or management of misfolded proteins.
Amyotrophic Lateral Sclerosis:
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. Our work in cell culture demonstrates that TDP-43 aggregates in response to stress, and we hypothesize that the pathway leading to TDP-43 accumulation contributes to the degeneration that occurs in amyotrophic lateral sclerosis.
We are using systems biology approaches, including context likelihood of relatedness (CLR) and mode-of-action by network identification (MNI), to analyze the network biology of Amyloid Precursor Protein (APP) processing and it’s trafficking partner, SORL1.
We are also examining whether Sirt1 agonists (such resveratrol, the compound found in red wine or SRT1720, produced by Sirtris Pharmaceuticals) offer protection in animal models of Parkinson’s disease.
In collaboration with Lewis Kazis we are using the Veteran’s Affairs Database to investigate medications, such as statins and Angiotensin Receptor Blockers, that appear to protect against dementia.
Saha S, Guillily MD, Ferree A, Lanceta J, Chan D, Ghosh J, Hsu CH, Segal L, Raghavan K, Matsumoto K, Hisamoto N, Kuwahara T, Iwatsubo T, Moore L, Goldstein L, Cookson M, Wolozin B. 2009. LRRK2 modulates vulnerability to mitochondrial dysfunction in Caenorhabditis elegans. J Neurosci.; 29(29):9210-8. PMID: 19625511
Oxysterol-binding protein-1 (OSBP1) modulates processing and trafficking of the amyloid precursor protein.
Zerbinatti CV, Cordy JM, Chen CD, Guillily M, Suon S, Ray WJ, Seabrook GR, Abraham CR, Wolozin B. 2008. Oxysterol-binding protein-1 (OSBP1) modulates processing and trafficking of the amyloid precursor protein. Mol Neurodegener.; 3:5. PMID: 18348724
Wolozin B, Wang SW, Li NC, Lee A, Lee TA, Kazis LE. 2007. Simvastatin is associated with a reduced incidence of dementia and Parkinson’s disease. BMC Med.; 5:20. PMID: 17640385
Takashima A, Shimojo M, Wolozin B. 2006. The players on the gamma-secretase team.
Nat Med.; 12(7):766-7; discussion 767. No abstract available. PMID: 16829940
Ved R, Saha S, Westlund B, Perier C, Burnam L, Sluder A, Hoener M, Rodrigues CM, Alfonso A, Steer C, Liu L, Przedborski S, Wolozin B. 2005. Similar patterns of mitochondrial vulnerability and rescue induced by genetic modification of alpha-synuclein, parkin, and DJ-1 in Caenorhabditis elegans. J Biol Chem.; 280(52):42655-68. Epub 2005 Oct 19. PMID: 16239214
Poon HF, Frasier M, Shreve N, Calabrese V, Wolozin B, Butterfield DA. 2005. Mitochondrial associated metabolic proteins are selectively oxidized in A30P alpha-synuclein transgenic mice–a model of familial Parkinson’s disease. Neurobiol Dis.;18(3):492-8. PMID: 15755676
Frasier M, Walzer M, McCarthy L, Magnuson D, Lee JM, Haas C, Kahle P, Wolozin B. 2005. Tau phosphorylation increases in symptomatic mice overexpressing A30P alpha-synuclein.
Exp Neurol.; 192(2):274-87. PMID: 15755545
Snyder H, Mensah K, Hsu C, Hashimoto M, Surgucheva IG, Festoff B, Surguchov A, Masliah E, Matouschek A, Wolozin B. 2005. beta-Synuclein reduces proteasomal inhibition by alpha-synuclein but not gamma-synuclein. J Biol Chem.; 280(9):7562-9. Epub 2004 Dec 9. PMID: 15591046
Technologies available for sharing upon request:
C. elegans assays; Real Time PCR; Protein aggregation assays; Protein Translation