Page 29 - Annual report 2021-22

Annual Report 2021-22 |

Ritushree Kukreti

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Ritushree Kukreti works on pharmacogenomics, to understand the varied responses of drugs used for
treating brain disorders, mainly epilepsies.

Epilepsy is characterized by recurrent seizures because of an uncontrolled activity in a group of
neurons. It is one of the most common neurological diseases in the world. Anti-epileptic drug (AED)
treatment is the initial choice for epilepsy management. However, inter-individual variability exists in
response to these AEDs. Some drugs show good efficacy in some people and others show poor
response. Some drugs can also cause adverse drug reactions in some patients. These differences in
the drug responses are primarily attributable to individual genetic differences, called
pharmacogenomic (PGx) variants.

Through her work, Ritushree aims to comprehend the genes and its variants involved in variable drug
response with a focus on drug metabolizing enzymes, efflux transporters and drug targets. The goal is
to present pre-emptively testing patients (before the drug is prescribed) for a panel of clinically
relevant PGx markers for commonly prescribed drugs for complex disorders. Pharmacogenomic
information for patient stratification is of value to tailor optimized treatment regimens thus
introducing a platform for early as well as efficient diagnosis and clinical recommendations. To this
end, the evaluation of correlation of a marker genotype to a specific phenotype, validation of the
statistical models and ascertaining the credibility of the genetic marker to be recommended as a
genetic test for clinical practice was performed using data collected from 1062 epilepsy patients and
498 age-matched healthy controls. The diagnostic predictability for PGx variants for specific anti-
epileptic drugs (AED) was tested by calculating the sensitivity and specificity to detect the risk allele
and the wild type allele.
Ritushree is also looking into the molecular regulators of drug metabolizing enzymes and the efflux
transporters involved in affecting AED response/ adverse effects. Improved understanding of the
regulatory events and identifying the signalling molecule affecting the expression of multidrug
transporter proteins will have a great potential for effective therapeutic intervention. Using a
combination of high-throughput genomic technologies, with in vitro functional assays, she aims to
elucidate the specific transcriptional modulators, which may serve to control the expression of such
transporters.

Altogether, developing knowledge resources to support precision medicine by screening for
polymorphisms associated with drug response phenotype and functionally validating the biomarkers
of clinical significance is the major objective of her lab.