Aimee Kao, MD, PhD

Professor in Residence
Department of Neurology
Research Overview: 

Despite intensive research efforts, many of the basic mechanisms underlying neurodegenerative diseases remain unclear.  We are tackling this problem by focusing on how aging, stress, gene variants and mutations alter protein homeostasis and lysosome function to predispose to neurodegeneration. Our recent work includes studies on the normal and abnormal metabolism of tau, TDP-43, progranulin and alpha-synuclein with a focus on how they are degraded by the proteases in the lysosome. We also consider how the lysosome function is regulated, including via pH set point and protease maturation.

For a recent overview of some of our work, please watch the video at this link

Primary Thematic Area: 
Neurobiology
Secondary Thematic Area: 
Human Genetics
Research Summary: 
Pathophysiology of Neurodegenerative Diseases: Aging, Stress, Lysosomes and Protein Homeostasis.
Mentorship Development: 

4/26/19    Sharpening your Mentoring Skills (SyMS) with Sharon Milgram (Mission Bay)    
11/23/20    Building Community in the UCSF MSTP 
9/11/20    Mentoring Across Differences
2/18/21    Three Truths and Three Tries: Facing and Overcoming Critical Social Justice Challenges at the Micro, Mezzo, and Macro Levels    

Websites

Publications: 

Postmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling.

Stem cell reviews and reports

Argouarch AR, Schultz N, Yang AC, Jang Y, Garcia K, Cosme CG, Corrales CI, Nana AL, Karydas AM, Spina S, Grinberg LT, Miller B, Wyss-Coray T, Abyzov A, Goodarzi H, Seeley WW, Kao AW

Phenotypic Screening Using High-Content Imaging to Identify Lysosomal pH Modulators in a Neuronal Cell Model.

ACS chemical neuroscience

Chin MY, Ang KH, Davies J, Alquezar C, Garda VG, Rooney B, Leng K, Kampmann M, Arkin MR, Kao AW

TSC1 loss increases risk for tauopathy by inducing tau acetylation and preventing tau clearance via chaperone-mediated autophagy.

Science advances

Alquezar C, Schoch KM, Geier EG, Ramos EM, Scrivo A, Li KH, Argouarch AR, Mlynarski EE, Dombroski B, DeTure M, Dickson DW, Yokoyama JS, Cuervo AM, Burlingame AL, Schellenberg GD, Miller TM, Miller BL, Kao AW

Processing of progranulin into granulins involves multiple lysosomal proteases and is affected in frontotemporal lobar degeneration.

Molecular neurodegeneration

Mohan S, Sampognaro PJ, Argouarch AR, Maynard JC, Welch M, Patwardhan A, Courtney EC, Zhang J, Mason A, Li KH, Huang EJ, Seeley WW, Miller BL, Burlingame A, Jacobson MP, Kao AW

Genetically Encoded, pH-Sensitive mTFP1 Biosensor for Probing Lysosomal pH.

ACS sensors

Chin MY, Patwardhan AR, Ang KH, Wang AL, Alquezar C, Welch M, Nguyen PT, Grabe M, Molofsky AV, Arkin MR, Kao AW