RESEARCH
AT A GLANCE
Profiled 1500+ trios from 10+ countries
Discovered 50+ new movement disorder causing genes
Identified 10+ candidate genes for Antisense Oligonucleotide (ASO) and drug repurposing
Enrolled 50+ cases with Deep Brain Stimulation
Collaborated across multiple countries in 6 continents
CURRENT AREAS OF STUDY
GENE DISCOVERY IN MOVEMENT DISORDERS
A major aspect of our research entails identifying genetic causes of pediatric movement disorders
Many neurodevelopmental and neurodegenerative disorders are of genetic origins. Cerebral Palsy (CP) is a major neurodevelopmental disorder with an estimate of over 30% of cases linked with genetic causes. Yet many causative genes remain undiscovered to this day, limiting the scope of personalized care. We leverage genomic sequencing data across diverse cohorts and advance more precise care for out patients and their families.
Our lab has been collaborating for many years with the CP Research Network consortium which seeks to establish gold standards for CP diagnosis and treatment. This collaboration has allowed the lab to launch a NIH-funded Genetic Causes of CP study, dedicated to understanding the genomic landscape of CP
Most recently, our team is also collaborating with The Translational Genomics Research Institute (TGen) to look in to the genetics of rare neurodevelopmental disorders with the aid of latest omics technologies that allows us to look into the non-expressed regions of the genome.
CALMING THE BRAIN
Modern medical technology has enabled us to calm a person's brain activity using small amounts of electric current. This is called deep brain stimulation.
Electrodes placed for deep brain stimulation (DBS) can also be used to 'listen' to the brain waves in real time. These brain waves are called local field potentials or LFPs.
Often in case of disorders like dystonia, and chorea, the brain demonstrates abnormal activity as indicated by LFP signals. We analyze and interpret these signals to identify patterns or trends, that can serve as neurophysiological biomarkers of these movement disorders.
Our goal is to utilize our findings to streamline in-clinic programming of DBS devices, as well as to optimize personalized DBS settings for every patient for enhanced treatment and care.
INNOVATION OF THERAPEUTIC STRATEGIES
Once we have an understanding of the mechanism that drives the disease, we need to develop innovative treatment strategies for those who are affected.
Building on genetic and mechanistic insights, our lab explores therapeutic strategies aimed at modifying disease at its source.
We are investigating different treatment strategies such as drug repurposing and antisense oligonucleotides (ASOs) to advance personalized care.
Drug repurposing aims at identifying existing compounds that can be redirected to target newly discovered pathways. ASOs aid in precisely modulating the gene expression of the culprit gene. By integrating computational analysis with experimental validation, we aim to accelerate the translation of molecular discoveries into targeted, effective treatments for pediatric movement disorders.
MECHANISMS OF HEALTH & DISEASE
Although identifying the genetic basis of a disorder represents a major achievement, it is often the first step to understanding the mechanisms involved.
Ongoing studies within the lab include studies of cellular CoA handling, the RHO GTPase pathway, and the integrated stress response.
We use a variety of techniques in order to understand both normal cellular biology and how genetic variants disrupt the trajectory of brain development. These encompass yeast models, mammalian cell lines (including patient-derived cells), Drosophila, neuronally differentiated iPSCs, and most recently human 'mini-brains' or brain organoids.
Within our research group, bioinformaticians and computational biologists, physicians, neuroscientists, geneticists, and molecular and cell biologists work side-by-side to answer challenging questions.
