Lennart Mucke, MD

Director
M_Neurology
[email protected]
+1 415 734-2504

Overview
Lennart Mucke’s laboratory aims to unravel how major neurologic and psychiatric conditions cause cognitive deficits, behavioral abnormalities, and other disabling symptoms, with an emphasis on dementias, epilepsy, and autism.

Our group uses mouse models and brain cell cultures to study disease-causing factors and pathways at molecular, cellular, network, and behavioral levels. Such models are also used to identify and validate novel entry points for therapeutic interventions.

The clinical relevance of discoveries is assessed through collaborative studies of human patients and brain tissues. Several findings we originally made in mouse models were subsequently identified for the first time in the human condition, highlighting the validity and power of experimental models. The most informative models have been used to identify novel strategies to counteract the development of brain dysfunctions and decline.

Major Contributions
• Instigated paradigm shifts in understanding and preventing the pathogenesis of Alzheimer’s disease

• Advanced the field from its traditional focus on morphological changes toward an understanding of Alzheimer’s disease at the synaptic and neural network level

• Defined molecular and cellular mechanisms underlying cognitive decline in Alzheimer’s disease

• Discovered unexpected links among Alzheimer’s disease, epilepsy and autism

• Identified novel therapeutic strategies and paved the path toward the development of tau-lowering therapeutics

• Provided critical guidance for the design of clinical trials aimed at reversing network hyperexcitability in Alzheimer’s disease

• Encouraged and enabled the translation of scientific discoveries into better treatments for brain diseases that are frequent, devastating, and costly to populations around the world

Interests and Ongoing Studies
• Mechanisms and treatment of dementia, epilepsy, and autism spectrum disorders

• Pathobiology of amyloid proteins, tau, apolipoprotein E, α-synuclein, TREM2, PTEN, and related signaling pathways

• Neural processes underlying important brain functions

• Role of glia in health and disease

• Dissection of complex neuropathogenic pathways in experimental models

• Development and (pre)clinical assessment of novel therapeutic strategies

• Establishment and guidance of interdisciplinary research programs

Publications

Fibrin-targeting immunotherapy protects against neuroinflammation and neurodegeneration.

Nature immunology

Ryu JK, Rafalski VA, Meyer-Franke A, Adams RA, Poda SB, Rios Coronado PE, Pedersen LØ, Menon V, Baeten KM, Sikorski SL, Bedard C, Hanspers K, Bardehle S, Mendiola AS, Davalos D, Machado MR, Chan JP, Plastira I, Petersen MA, Pfaff SJ, Ang KK, Hallenbeck KK, Syme C, Hakozaki H, Ellisman MH, Swanson RA, Zamvil SS, Arkin MR, Zorn SH, Pico AR, Mucke L, Freedman SB, Stavenhagen JB, Nelson RB, Akassoglou K

The Psychiatric Cell Map Initiative: A Convergent Systems Biological Approach to Illuminating Key Molecular Pathways in Neuropsychiatric Disorders.

Cell

Willsey AJ, Morris MT, Wang S, Willsey HR, Sun N, Teerikorpi N, Baum TB, Cagney G, Bender KJ, Desai TA, Srivastava D, Davis GW, Doudna J, Chang E, Sohal V, Lowenstein DH, Li H, Agard D, Keiser MJ, Shoichet B, von Zastrow M, Mucke L, Finkbeiner S, Gan L, Sestan N, Ward ME, Huttenhain R, Nowakowski TJ, Bellen HJ, Frank LM, Khokha MK, Lifton RP, Kampmann M, Ideker T, State MW, Krogan NJ

Life extension factor klotho enhances cognition.

Cell reports

Dubal DB, Yokoyama JS, Zhu L, Broestl L, Worden K, Wang D, Sturm VE, Kim D, Klein E, Yu GQ, Ho K, Eilertson KE, Yu L, Kuro-o M, De Jager PL, Coppola G, Small GW, Bennett DA, Kramer JH, Abraham CR, Miller BL, Mucke L

A roadmap for the prevention of dementia II: Leon Thal Symposium 2008.

Alzheimer's & dementia : the journal of the Alzheimer's Association

Khachaturian ZS, Snyder PJ, Doody R, Aisen P, Comer M, Dwyer J, Frank RA, Holzapfel A, Khachaturian AS, Korczyn AD, Roses A, Simpkins JW, Schneider LS, Albert MS, Egge R, Deves A, Ferris S, Greenberg BD, Johnson C, Kukull WA, Poirier J, Schenk D, Thies W, Gauthier S, Gilman S, Bernick C, Cummings JL, Fillit H, Grundman M, Kaye J, Mucke L, Reisberg B, Sano M, Pickeral O, Petersen RC, Mohs RC, Carrillo M, Corey-Bloom JP, Foster NL, Jacobsen S, Lee V, Potter WZ, Sabbagh MN, Salmon D, Trojanowski JQ, Wexler N, Bain LJ

Genes contributing to prion pathogenesis.

The Journal of general virology

Tamgüney G, Giles K, Glidden DV, Lessard P, Wille H, Tremblay P, Groth DF, Yehiely F, Korth C, Moore RC, Tatzelt J, Rubinstein E, Boucheix C, Yang X, Stanley P, Lisanti MP, Dwek RA, Rudd PM, Moskovitz J, Epstein CJ, Cruz TD, Kuziel WA, Maeda N, Sap J, Ashe KH, Carlson GA, Tesseur I, Wyss-Coray T, Mucke L, Weisgraber KH, Mahley RW, Cohen FE, Prusiner SB

Affiliation
Committee Members