Lawrence Goldstein

About

Lawrence Goldstein is an Emeritus Professor of Cellular and Molecular Medicine at UCSD. His research focuses on unraveling how molecular motors interact with and control the behavior of axonal vesicles, and relating this understanding to the molecular basis of neuronal defects in Alzheimer's Disease (AD) and Niemann Pick type C disease. His work utilizes pluripotent stem cell lines containing known mutations that cause hereditary Alzheimer's disease and Niemann Pick Type C disease, with the aim of understanding cholesterol trafficking and transport in relation to dementia. Goldstein's lab also probes basic mechanisms of vesicle movement and sorting in neurons, and how genetic variation predisposes individuals to different neuronal phenotypes and diseases, including sporadic Alzheimer's disease. He has developed quantitative methods for generating and evaluating neurons from human embryonic stem cells and induced pluripotent stem cells, and collaborates on developing potential therapies for ALS using human embryonic stem cells to generate astrocyte progenitors. His research areas include genetics and genomics, membrane trafficking, neurodevelopment, and neurodegenerative disease.

Research topics

• Biology
• Cell biology
• Genetics
• Neuroscience
• Internal medicine
• Biochemistry

Selected publications

• Amyloid-β-independent regulators of tau pathology in Alzheimer disease

  Nature reviews. Neuroscience · 2019-11-28 · 565 citations

  reviewOpen access
  PublisherOA PDFDOI

• Cholesterol Metabolism Is a Druggable Axis that Independently Regulates Tau and Amyloid-β in iPSC-Derived Alzheimer’s Disease Neurons

  Cell stem cell · 2019-01-27 · 366 citations

  articleOpen accessSenior authorCorresponding

  Genetic, epidemiologic, and biochemical evidence suggests that predisposition to Alzheimer's disease (AD) may arise from altered cholesterol metabolism, although the molecular pathways that may link cholesterol to AD phenotypes are only partially understood. Here, we perform a phenotypic screen for pTau accumulation in AD-patient iPSC-derived neurons and identify cholesteryl esters (CE), the storage product of excess cholesterol, as upstream regulators of Tau early during AD development. Using i…

  PublisherOA PDFDOI

• Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer’s patients

  Cell stem cell · 2021 · 244 citations

  PublisherOA PDFDOI

• Stabilizing the Retromer Complex in a Human Stem Cell Model of Alzheimer’s Disease Reduces TAU Phosphorylation Independently of Amyloid Precursor Protein

  Stem Cell Reports · 2018-03-01 · 126 citations

  articleOpen accessSenior authorCorresponding

  Developing effective therapeutics for complex diseases such as late-onset, sporadic Alzheimer's disease (SAD) is difficult due to genetic and environmental heterogeneity in the human population and the limitations of existing animal models. Here, we used hiPSC-derived neurons to test a compound that stabilizes the retromer, a highly conserved multiprotein assembly that plays a pivotal role in trafficking molecules through the endosomal network. Using this human-specific system, we have confirmed…

  PublisherOA PDFDOI

• Full-length amyloid precursor protein regulates lipoprotein metabolism and amyloid-β clearance in human astrocytes

  Journal of Biological Chemistry · 2018-06-01 · 75 citations

  articleOpen accessSenior authorCorresponding

  astrocytes reversed the LDL and Aβ endocytosis defects. In conclusion, FL APP is involved in the endocytosis of LDL receptor ligands and is required for proper cholesterol homeostasis and Aβ clearance in human astrocytes.

  PublisherDOI

Recent grants

• NIH Grant RC1NS068705

  NIH · $1.0M · 2012

• NIH Grant R01GM035252

  NIH · $5.1M · 2007

• NIH Grant R21AG038849

  NIH · $336k · 2013

Frequent coauthors

• Elizabeth A. Roberts

  University of California, San Diego

  65 shared

• Fred H. Gage

  Salk Institute for Biological Studies

  56 shared

• Austin Smith

  53 shared

• Irving L. Weissman

  Stanford University

  52 shared

• Fiona M. Watt

  European Molecular Biology Organization

  50 shared

• Rudolf Jaenisch

  Whitehead Institute for Biomedical Research

  50 shared

• J. B. Gurdon

  University of Cambridge

  50 shared

• Ernest Memorial

  Wellcome/MRC Cambridge Stem Cell Institute

  50 shared

Education

• Ph.D., Molecular Biology

  University of California, San Diego

  1981

• B.S., Biology

  University of California, San Diego

  1976

Similar researchers at University of California, San Diego

• Christopher Glassh-185
• Richard Kolodnerh-146
• Jeffrey Eskoh-99