Research Summary
My team has diversified interest on complex disorders of brain with specific interest on genetics and epigenetics and developing tools for personalised medicine. Fundamental aspects of complex disorders lies in its population and its environment, which is responsible for its phenotypic, metabolomic and biochemical diversities. Therefore, before getting into the complex diseases of brain we first used population genetics approach for population stratification and then for epigenetic stratification we considered epigenetic genes and similar dietary and environmental parameters. Population stratification was carried out using non-functional markers, such as microsatellite markers, and functional markers like immunogenetic markers (HLA, Cytokines) and Pharmacogenomics markers (drug target, drug metabolism and drug transporter genes) and epigenetic genes was used for epigenomic stratification. In the quest for complex diseases we use different approaches for genetic and epigenetic observations. For genetics, we use pathway-based genes, functional domains-based genes such as immunogenetics, pharmacogenetics and epigenetic genes, genomewide microarray and whole exome. For epigenetics we use gene specific and genomewide methylation, individual miRNA and genome wide microRNA and histone modifications. In our investigations we also use individual metabolite to complete metabolomic screening, metagenomic approaches and extensive In-Silico genomics, bioinformatics and systems approach.
In most of the diseases that we work there is no precise biochemical or phenotypic marker which makes diagnosis and therapy even more difficult. Some of our work on population genetics has become a part of Kerala folklore. With our background on population genetics our investigations on complex neurological and neuropsychiatric disorders became simpler. Presently we are involved in investigating the genetic, immunogenetics, pharmacogenetics, and epigenetics of complex diseases such as Schizophrenia, Autism, Cerebral stroke (Aneurysm), Dementia, Epilepsy (paediatric and adult), Suicide, Cancer, Parkinsons and Hearing loss. Most of these works are being carried out with extensive collaborations within and outside the country with excellent team of researchers and clinicians from many referral centers, medical and dental institutions around the globe.
In most of the diseases that we work there is no precise biochemical or phenotypic marker and diagnosis can be difficult. My team has demonstrated the genetics of symptomatology in Schizophrenia (Behav Brain Function 2007, J Hum Genetics, 2009, IJMR, 2014) and the role of chronic exposure to altered immune response in development of Schizophrenia (J.Neuroinflammation 2016, J Psychiatric Res., 2018). In addition we for the first time demonstrated that genetics of epigenome are critical in deciding the altered epigenetic response in development of schizophrenia (PlosOne 2014). This work on genetics of epigenome is fast becoming prominent in many complex disorders. We ourselves have demonstrated its role, not only in schizophrenia but also in Aneurysm, Autism, Epilepsy and Dementia (Epigenomics 2020, IUBMB Life 2018). Several studies worldwide has discussed the role of epigenomic alterations in Schizophrenia, however, we have questioned these observations and demonstrated that a large majority of the epigenetic observations are not characteristics of its pathology but instead they are drug induced alterations. This field of pharmacoepigenomics in schizophrenia has been extensively demonstrated and validated in our studies (Epigenomics 2017, 2018, 2019, PlosOne 2017) which in return will help in fine tuning the personalized medication. In many of these diseases drug response and side effects are a matter of concern. Our work on genetics and pharmacogenetics of schizophrenia and epilepsies demonstrates the genetic signatures of treatment response and malformations associated with the drugs (Drug. Metab. Pharmacokinet 2009, Pharmacogenomics 2012, Pharmacogenetics and Genomics.2013, Gene 2013, Epilepsy Res.2012, IANS, 2014, PloSOne 2014). Our work on genetics, epigenetics and metabolomics of Intracranial aneurysm has also been extensively published (Disease Markers 2008, Cerebrovascular Disease, 2010, Mol Biology Reports 2013, J Neuroinflammation 2015). Now we have developed an GERS score (Gene Environment Risk score) for aneurysm. We proposed a novel immunological hypothesis in Non-Syndromic deafness (Front Immunol. 2019) which is undergoing validation.
My team has developed several technologies.
Developed and validated four STR based DNA fingerprinting markers.
Method for generating 100bp ladder for endless usage.
RAGEP PCR: A novel method for assessing biodiversity and genetic variation.
A STR based multiplex kit for determining Ankylosing spondilytis
Allele Typer a Windows based Allele typing software used for mutation studies.
Genome Profile Analysis software, Windows based for mutation analysis on genes of Pharmacogenomic and Immunogenetic interests.
Genopack a Linux based software for Allele sequence matching, Sequence Alignment, Complementary and reverse complementary strand generation, Protein translation, Position Matching, Motif matching, Restriction Mapping, Consensus sequence generation, searching for open reading frames and the corresponding patterns and supports Format conversion.
Psychiatric disease management software, to be used for predictive medicine.
