GENOMICS & BIOLOGY OF NEUROLOGICAL DISEASES

Dr. Binukumar B.K.’s research program is centered on understanding the genomic and molecular mechanisms underlying neurological and metabolic disorders, with a strong emphasis on rare disease genomics. His lab integrates patient-derived stem cell models and large-scale clinical collaborative networks to unravel disease mechanisms and identify potential therapeutic targets.

Key focus areas include:

• Rare disease genomics and collaborative networks:

  • Initiated the Indian Collaborative Research Network on Wilson’s Disease (ICROWD), now comprising over 45 clinicians from 40+ centers, to decode the genetic epidemiology of Wilson’s disease in India.

  • Established genomic variant resources such as WilsonGen and WilsonGenAI, providing clinically annotated variant databases and AI-driven pathogenicity prediction tools for Wilson’s disease.

  • Reported several first-in-India and novel global findings, including rare ATP7B variants and co-occurrence of Wilson’s disease with other neurogenetic syndromes (e.g., KMT2B dystonia).

• Patient-specific stem cell and organoid models:

  • Developed multiple iPSC lines from Wilson’s disease patients, including those carrying compound heterozygous or rare pathogenic variants, to investigate molecular pathology.

  • Applied CRISPR/Cas9 genome editing to generate isogenic controls and study phenotypic outcomes of disease-associated variants.

  • Differentiated iPSCs into brain cell types and organoids to model neurodegeneration, enabling both mechanistic studies and therapeutic screening.

• Expanding the genetic landscape of movement disorders:

  • Conducted the first comprehensive analysis of the genetic landscape of dystonia in Asian Indians, uncovering novel variants and pathways.

  • Contributed to systematic reviews and clinical guidelines on deep brain stimulation for KMT2B-related dystonia.

• Molecular mechanisms of neurodegeneration and comorbidities:

  • Elucidated Cdk5-mediated pathways in neurodegeneration, linking Type 2 Diabetes Mellitus and Alzheimer’s disease.

  • Identified disrupted kinase cross talk, mitochondrial dysfunction, and unfolded protein response as critical drivers of cognitive decline.

  • Demonstrated the therapeutic potential of Cdk5 inhibitors and neuroprotective peptides in restoring cognitive and metabolic functions in preclinical models.

Impact:
Through a combination of rare disease genomics, stem cell modeling, and collaborative research, the lab has advanced the understanding of Wilson’s disease, dystonia, and related neurodegenerative disorders. This translational approach not only improves genetic diagnosis in Indian populations but also opens avenues for precision medicine and targeted therapies.

Join The Lab