Lennart Mucke’s lab focuses on how major neurological and psychiatric conditions, such as Alzheimer’s disease and autism spectrum disorders, cause cognitive deficits, behavioral abnormalities, and other disabling symptoms. They study people afflicted by these conditions, as well as related mouse and cell culture models, to unravel disease mechanisms and identify novel therapeutic strategies. The group’s ultimate goal is to advance the understanding of devastating brain disorders to a point where transformative treatments can be developed for their prevention, control, and reversal.

Disease Areas

Alzheimer’s Disease
Autism Spectrum Disorders
Epilepsy
Other Dementias

Areas of Expertise

Creation and Direction of Interdisciplinary Research Programs
Development and Preclinical Assessment of Novel Therapeutic Strategies
Dissection of Complex Pathogenic Pathways in Mouse Models
Pathobiology of Amyloid Proteins and Tau
Role of Glia in Health and Disease
Training of Leaders in Disease-Focused Neuroscience
Gladstone_ZhuLei_MuckeLab.png

Lab Focus

Mechanisms and pathogenic impact of neural network dysfunction and DNA damage in Alzheimer’s disease and related conditions.
Understanding the roles of tau and glial cells in health and disease.
Therapeutic strategies targeting tau or other molecules that promote neuronal impairments in major neurological and psychiatric disorders.

Research Impact

Mucke’s studies revealed that Aβ and apoE4 can elicit neuronal deficits independently of amyloid plaques and that Aβ causes not only synaptic depression, but also neural network hyperexcitability. He discovered that reducing neuronal tau levels prevent network hyperexcitability of diverse causes and is well tolerated, revealing a novel role for tau in the regulation of neuronal activity and challenging the long-standing notion that tau aggregation causes neurodegeneration through loss of tau functions.

These discoveries paved the path toward the development of tau-lowering therapeutics, which is now pursued in academic laboratories and pharmaceutical companies around the world. Mucke’s investigations of patients with Alzheimer’s and related models also shed new light on the intriguing overlap between Alzheimer’s disease and epilepsy, culminating in the discoveries that a substantial proportion of Alzheimer’s patients have subclinical, non-convulsive epileptiform activity and that the suppression of such activity in animal models can reverse synaptic and cognitive deficits. These insights provided critical guidance for the design of ongoing clinical trials aimed at reversing network dysfunction in early stages of Alzheimer’s disease. Mucke has advanced this field from its traditional focus on morphological changes toward an understanding of Alzheimer’s disease at the synaptic and neural network level and identified novel therapeutic strategies in a field in desperate need of them. In addition, he has developed novel strategies to expedite the translation of scientific discoveries into better treatments for diseases that are frequent, devastating, and costly to populations around the world.

 

Professional Titles

Director, Gladstone Institute of Neurological Disease

Senior Investigator, Gladstone Institutes

Joseph B. Martin Distinguished Professor of Neuroscience and Professor of Neurology, UC San Francisco

Bio

Lennart Mucke is the director of the Gladstone Institute of Neurological Disease, and a senior investigator at Gladstone. He is also the Joseph B. Martin Distinguished Professor of Neuroscience and a professor of neurology at UC San Francisco (UCSF). He has joint appointments in UCSF’s Neuroscience, Biomedical Sciences, and Medical Scientist (MD/PhD) Graduate Training Programs.

Mucke is a graduate of the Georg-August University and the Max Planck Institute for Biophysical Chemistry (Neurobiology) in Göttingen, Germany. He trained in internal medicine at the Cleveland Clinic, in neurology at Massachusetts General Hospital and Harvard Medical School, and in neuroimmunology and neurovirology at The Scripps Research Institute, where he was subsequently appointed to the faculty. Mucke was recruited to Gladstone Institutes in 1996.

How Did You Get Your Start in Science?

“I developed a great interest in psychiatry, neurology, and neuroscience in high school and to this day can’t think of anything more fascinating and rewarding than to discover how the brain works and how to preserve the fragile structures that harbor the very essence of who we are.”

Lennart Mucke, MD

Honors and Awards

2019 Fellow of the German Center for Neurodegenerative Diseases (DZNE)

2013 MetLife Award for Medical Research in Alzheimer’s Disease, MetLife Foundation

2013 American Pacesetter Award, ARCS Foundation

2013 J. Elliott Royer Award for Excellence in Academic Neurology, UC San Francisco

2012 Khalid Iqbal Lifetime Achievement Award in Recognition of Outstanding Research, Alzheimer’s Association

2012 Honorary Citizen of New Orleans

2011 Chancellor’s Award in Neurosciences, Louisiana State University

2010 Potamkin Prize for Research in Pick’s, Alzheimer’s, and Related Diseases, American Academy of Neurology

2007 Award for Excellence in Direct Teaching and/or Excellence in Mentoring and Advising, Haile T. Debas Academy of Medical Educators

2006 Arthur Cherkin Memorial Award, UCLA

2003 Promising Investigator Award, MetLife Foundation

2003 Elected to the Association of American Physicians

1999 Zenith Award, Alzheimer’s Association

1998 Elected to the American Neurological Association

Publications

More Publications

Contact

Lennart Mucke

415.734.2504

Jordan Rosendorf
Administrative Assistant I
415.734.4857


Lab Members

Amandine Berthet, PhD
Visiting Scientist
Che-Wei Chang, PhD
Postdoctoral Scholar
Melanie Das, PhD
Scientist
Daniel Gulbranson, PhD
Postdoctoral Scholar
Kaitlyn Ho
Senior Research Associate
Daniel Kim
Research Scientist
Wenjie Mao, PhD
Postdoctoral Scholar
Lisa McConlogue, PhD
Visiting Scientist
Laura Mitic, PhD
Visiting Scientist
Cathrine Petersen
Graduate Student
Eric Shao, PhD
Postdoctoral Scholar
Yasemin Sucu
Research Associate II
Xin Wang
Research Associate III
Jiaming Wang, MS
Research Associate II
Xing Yu
Research Associate II
Gui-Qiu Yu, MS
Research Scientist