Zhu Laboratory

Genetics, epigenetics and therapeutic innovation in neurodegenerative diseases

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease that causes progressive loss of voluntary muscle control and movement, and that leads to total paralysis and death within two to five years of diagnosis. Frontotemporal dementia (FTD) is an umbrella term for a group of neurological disorders clinically characterized by degeneration of the frontal and/or temporal lobes of the brain. FTD patients suffer from personality and behavioral changes, gradual language impairment and other symptoms. FTD is the most common form of dementia for people under age 60. Currently, there is no cure for either ALS or FTD. There can be significant costs for medical care, equipment and home health caregiving later in the disease.

The Zhu Laboratory seeks to reveal the mechanisms that give rise to these devastating diseases and to leverage this knowledge to develop novel strategies for slowing or stopping disease progression. One of the lab’s main research focuses is the large hexanucleotide repeat expansion in the C9ORF72 gene, which is the most common genetic cause for both genetic-inherited familiar ALS and FTD, and also affects a large portion of sporadic cases without family history. Through in-depth studies on this mutation, we can enhance understanding of the mechanistic basis of cognitive and motor activities and answer fundamental questions about motor dysfunction and mental illness, with a particular focus on cell-type specific toxicities, neuron-glia interactions, genetics and epigenetics. To address these challenges, we integrate interdisciplinary approaches including new disease model generation based on genome-modified animals and human iPSCs, CRISPR gene editing, locus-specific epigenetic modification and behavioral neuroscience.

We also will build on previous work by Dr. Zhu, colleagues and biotech industry partners that leads to an antisense oligonucleotide (ASO)-mediated therapy in clinical trials for treating the repeat disease. We expect to discover new drug targets or biomarkers by cutting-edge large-scale screening and single-cell multiomics and develop therapies for neurological disorders through ASO, small-molecule drug, AAV-mediated gene therapy or other novel methods.