Mission Statement: The Varshney lab is dedicated to pioneering advancements in genetic research, directly impacting the understanding and treatment of human diseases through innovative tools and collaborative efforts. Varshney lab’s research is centered on three main themes:
1. Cutting-edge CRISPR-based Genome Editing Technologies
Our lab focuses on developing and optimizing advanced CRISPR-based genome editing methods. We are at the forefront of creating highly efficient base editors and expanding the CRISPR toolkit to enhance the functional analysis of genetic variants. Key projects include:
- Next-generation Base Editors: Development of Adenine and Cytosine base editors that offer higher editing efficiency, flexible PAM requirements, and reduced off-target effects.
- High-throughput Functional Screening: Implementing streamlined CRISPR/Cas9 workflows to rapidly generate and phenotype biallelic mutations in zebrafish, significantly shortening the time required to link genetic variants to their functional outcomes.
2. Understanding Neurological Disorders and Hearing Impairment
We delve into the mechanistic insights of novel candidate genes associated with a range of neurological and neurodevelopmental disorders and hearing impairments. Our research aims to elucidate the genetic underpinnings and pathogenic mechanisms, facilitating the development of therapeutic interventions. Highlights include:
- Functional Analysis of Neurological Genes: Using zebrafish models to study genes encoding nuclear-encoded mitochondrial genes, tRNA synthetase genes, and others identified through international collaborations.
- Hearing Impairment Pathologies: Investigating genes involved in sensorineural hearing loss, with successful models replicating human clinical phenotypes, aiding in understanding and potentially treating these conditions.
3. In Vivo Functional Analysis of Non-coding Variants from GWAS
Our lab is pioneering methods to explore the functional implications of non-coding variants identified through genome-wide association studies (GWAS). This research aims to uncover the regulatory roles of these variants and their contributions to complex human diseases. Key initiatives include:
- Characterizing Conserved Non-exonic DNA Elements (CNEs): Collaborating with Stanford University (Dr. Philippe Mourrain) to identify and functionally validate non-coding SNPs that are evolutionarily conserved, linking them to various human traits and conditions.
- Hearing Impairment GWAS Loci: Functional validation of genes identified through GWAS associated with age-related and non-syndromic hearing impairment using zebrafish models.
Key Achievements:
- Developed high-throughput workflows for targeted mutagenesis in zebrafish, significantly accelerating the timeframe for uncovering gene function.
- Identified and validated numerous candidate disease genes in collaboration with international research networks, enhancing our understanding of their roles in neurological and hearing impairment disorders.
- Created a comprehensive library of zebrafish models for studying hearing impairment genes, enabling detailed investigations into their genetic and molecular mechanisms.
Collaborations: We actively partner with researchers worldwide, including collaborations with the Undiagnosed Diseases Network and international experts in hearing loss and neurodevelopmental disorders. These partnerships are crucial in accessing diverse genetic data and accelerating the discovery of disease-causing genes.
Innovate | Impact | Collaborate
- Innovate: We develop pioneering genetic tools and apply novel approaches to studying disease genes.
- Impact: Our research directly contributes to understanding human disease and identifying potential therapeutic targets.
- Collaborate: We actively partner with international researchers to accelerate the discovery of disease-causing genes.