Ritushree Kukreti

Institute of Genomics and Integrative Biology | IGIB · Genomics and Molecular Medicine Unit (IGIB)

This work primarily focusses on the role of Desmoplakin, a cell adhesion molecule in the development of idiopathic pulmonary fibrosis (IPF).

Epilepsy treatment is challenging due to heterogeneous syndromes, different seizure types and higher inter-individual variability. Identification of genetic variants predicting drug efficacy, tolerability and risk of adverse-effects for anti-seizure medications (ASMs) is essential. Here, we assessed the clinical actionability of known genetic varia...

Background: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disorder of unknown cause, affecting about three million people worldwide. Being a multifactorial disease, complex genetic and environmental factors contribute to its susceptibility. Therefore, we conducted a two-staged systematic literature search and meta-analyses of published gen...

Background: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disorder of unknown cause, affecting about three million people worldwide. Being a multifactorial disease, complex genetic and environmental factors contribute to its susceptibility. Many genetic association studies have been published to date, but studies have reported conflicting...

The brain, one of the most resilient organs of the body is highly enriched in lipid content, suggesting the essential role of lipids in brain physiological activities. Lipids constitute an important structural part of the brain and act as a rich source of metabolic energy. Besides, lipids in their bioactive form (known as bioactive lipids) play an...

Background: The clinical heterogeneity in major depressive disorder (MDD), variable treatment response and conflicting findings limit the ability of genomics towards the discovery of evidence-based diagnosis and treatment regimen. This study attempts to curate all genetic association findings to evaluate potential variants for clinical translation...

The humancytochrome P450 1A (CYP1A) subfamily genes, CYP1A1 and CYP1A2, encoding monooxygenases are critically involved in biotransformation of key endogenous substrates (estradiol, arachidonic acid, cholesterol) and exogenous compounds (smoke constituents, carcinogens, caffeine, therapeutic drugs). This suggests their significant involvement in mu...

Despite the progress made in the development of new antiepileptic drugs (AEDs), poor response to them is a rising concern in epilepsy treatment. Of several hypotheses explaining AED treatment failure, the most promising theory is the overexpression of multidrug transporters belonging to ATP-binding cassette (ABC) transporter family at blood-brain b...

Pneumonia, an acute respiratory tract infection, is one of the major causes of mortality worldwide. Depending on the site of acquisition, pneumonia can be community acquired pneumonia (CAP) or nosocomial pneumonia (NP). The risk of pneumonia, is partially driven by host genetics. CYP1A1 is a widely studied pulmonary CYP family gene primarily expres...

Abstract Oxidative stress (OS) is a metabolic dysfunction mediated by the imbalance between the biochemical processes leading to elevated production of reactive oxygen species (ROS) and the antioxidant defense system of the body. It has a ubiquitous role in the development of numerous noncommunicable maladies including cardiovascular diseases, canc...

Multimodal or combination therapy has been considered as a powerful approach for treatment of complex diseases like cancer. The fascinating physicochemical and optoelectronic properties of gold nanoparticles make them potential candidate for cancer therapeutic and diagnostic applications. Herein, we design a multifunctional nanosystem by conjugatin...

Neurodegenerative diseases are conditions characterized by irreversible loss of neurons and loss of cognitive and motor function, mostly occurring in elderly people. The increasing age has been the most consistent risk factor for developing a neurodegenerative disorder. Interlinking of oxidative stress and neurodegeneration is well established, ind...

Citation: Mishra, M.K.; Kukal, S.; Paul, P.R.; Bora, S.; Singh, A.; Kukreti, S.; Saso, L.; Muthusamy, K.; Hasija, Y.; Kukreti, R. Insights into Structural Modifications of Valproic Acid and Their Pharmacological Profile. Molecules 2022, 27, 104. https:// Abstract: Valproic acid (VPA) is a well-established anticonvulsant drug discovered serendipitou...

Previously, we demonstrated an integrated genomic convergence and network analysis approach to identify the candidate genes associated with the complex neurodegenerative disorder, Alzheimer’s disease (AD). Here, we performed a pilot study to validate the in silico approach by studying the association of genetic variants from three identified critic...

The adenosine triphosphate (ATP)-binding cassette efflux transporter G2 (ABCG2) was originally discovered in a multidrug-resistant breast cancer cell line. Studies in the past have expanded the understanding of its role in physiology, disease pathology and drug resistance. With a widely distributed expression across different cell types, ABCG2 play...

The risk for community acquired pneumonia (CAP) is partially driven by genetics. To identify the CAP-associated genetic risk loci, we performed a meta-analysis of clinically diagnosed CAP (3310 individuals) with 2655 healthy controls. The findings revealed CYP1A1 variants (rs2606345, rs4646903, rs1048943) associated with pneumonia. We observed rs26...

Moderate levels of endogenous reactive oxygen species (ROS) are important for various cellular activities, but high levels lead to toxicity and are associated with various diseases. Levels of ROS are maintained as a balance between oxidants and antioxidants. Accumulating data suggest that oxidative stress is a major factor in deterioration of renal...

With the advent of DNA sequencing technology that led to the human genome project, there was an explosion of big data in the field of biomedical sciences. The successful completion of the human genome project led to the emergence of numerous fields for data-driven discovery like genomics, proteomics, and bioinformatics per se. It was expected that...

[This corrects the article DOI: 10.3389/fphar.2019.00839.].

Epilepsy, a neurological disease characterized by recurrent seizures, is highly heterogeneous in nature. Based on the prevalence, epilepsy is classified into two types: common and rare epilepsies. Common epilepsies affecting nearly 95% people with epilepsy, comprise generalized epilepsy which encompass idiopathic generalized epilepsy like childhood...

Antiepileptic drug therapy has significant inter-patient variability in response towards it. The current study aims to understand this variability at the molecular level using microarray-based analysis of peripheral blood gene expression profiles of patients receiving valproate (VA) monotherapy. Only 10 unique genes were found to be differentially...

Prostaglandin E2 (PGE2), a physiologically active lipid compound, is increased in several diseases characterized by chronic inflammation. To determine its significance in epilepsy-associated inflammation and response to antiepileptic drug (AED), we evaluated the plasma PGE2 (median, pg/ml) levels in drug-free patients with epilepsy (N=34) and patie...

Epilepsy, a common multifactorial neurological disease, affects about 69 million people worldwide constituting nearly 1% of the world population. Despite decades of extensive research on understanding its underlying mechanism and developing the pharmacological treatment, very little is known about the biological alterations leading to epileptogenes...

Purpose: The major goal of epilepsy management using antiepileptic drug therapy is to attain seizure freedom without any adverse effects. However, the reported adverse effects of antiepileptic drugs on the hematological and biochemical profiles are subject of considerable debate in clinical practice. The objective of the present study was to invest...

Over the decades, oxidative stress has emerged as a major concern to biological researchers. It is involved in the pathogenesis of various lifestyle-related diseases such as hypertension, diabetes, atherosclerosis, and neurodegenerative diseases. The connection between oxidative stress and telomere shortening via oxidative guanine lesion is well do...

Background: Hypertension is a prevalent cardiovascular complication caused by genetic and nongenetic factors. Blood pressure (BP) management is difficult because most patients become resistant to monotherapy soon after treatment initiation. Although many antihypertensive drugs are available, some patients do not respond to multiple drugs. Identifi...

Understanding patients’ genomic variations and their effect in protecting or predisposing them to drug response phenotypes is important for providing personalized healthcare. Several studies have manually curated such genotype–phenotype relationships into organized databases from clinical trial data or published literature. However, there are no te...

Abstract Oxidative stress is proposed as a regulatory element in ageing and various neurological disorders. The excess of oxidants causes a reduction of antioxidants, which in turn produce an oxidation–reduction imbalance in organisms. Paucity of the antioxidant system generates oxidative-stress, characterized by elevated levels of reactive species...

Despite numerous studies on major depressive disorder (MDD) susceptibility, the precise underlying molecular mechanism has not been elucidated which restricts the development of etiology-based disease-modifying drug. Major depressive disorder treatment is still symptomatic and is the leading cause of (~30%) failure of the current antidepressant the...

Heterogeneity in epilepsy often interferes with its diagnosis as well as treatment. To examine this heterogeneity at transcriptomic level, we performed whole-genome mRNA expression profiling in whole blood samples from 34 patients with epilepsy (PWE) (idiopathic, n = 13; cryptogenic, n = 9; and symptomatic, n = 12) and 41 healthy controls (HC) usin...

Quasi-palindromic sequences (AT)XN12(AT)Y present in HS2 (hypersensitive site 2) of the human β-globin locus are known to be significantly associated with increased fetal hemoglobin (HbF) levels. High HbF levels in some adults arise due to pathological conditions such as sickle cell disease and β-thalassemia. However, elevated levels of HbF are als...

Background: Nearly 40%–50% of the individuals fail to respond to first line antiepileptic drug (AED) monotherapy and 30% are refractory, which calls for the need to recognize predictive markers for treatment failure. This study aims to identify clinical factors predictive of a poor prognosis in patients on AED therapy. Materials and Methods: A pros...

Alzheimer's disease (AD) is genetically complex with multifactorial etiology. Here, we aim to identify the potential viral pathogens leading to aberrant inflammatory and oxidative stress response in AD along with potential drug candidates using systems biology approach. We retrieved protein interactions of amyloid precursor protein (APP) and tau pr...

A gradual dementia, which leads to the loss of memory and intellectual abilities, is the main characteristics of Alzheimer’s disease. Amyloid-β (Aβ) plaques are the main components that accumulate and form clumps in the brains of people suffering from Alzheimer’s disease. Apolipoprotein E (APOE), an amyloid-binding protein is considered as one of t...

Interactions amongst different amyloid proteins have been proposed as a probable mechanism of aggregation and thus an important risk factor for the onset as well as progression of various neurodegenerative disorders including Alzheimer's, Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis. Evidences suggest that transthyretin (TTR), a pla...

Background and Objectives: Vitamin D Receptor (VDR) gene polymorphism has long been known for its association with Chronic Kidney Disease (CKD). We aimed to investigate the potential role of VDR gene polymorphisms in CKD patients. Design and Methods: The association of VDR gene polymorphisms in CKD patients (N=147; males =100 (68.03%) and females=4...

A gradual dementia, which leads to the loss of memory and intellectual abilities, is the main characteristics of Alzheimer’s disease. Amyloid-β (Aβ) plaques are the main components that accumulate and form clumps in the brains of people suffering from Alzheimer’s disease. Apolipoprotein E (APOE), an amyloid-binding protein is considered as one of t...

The criteria for dose and drug selection are based on clinical studies. Generally a standard empiric dose of a drug is defined which provides an optimum benefit to patients. But in some cases this empiric drug-dose concept does not work properly. There are many factors, like disease severity, patient’s age, gender, weight, etc., which influence dru...

ABC transporters have a significant role in drug disposition and response and various studies have implicated their involvement in epilepsy pharmacoresistance. Since genetic studies till now are inconclusive, we thought of investigating the role of xenobiotics as transcriptional modulators of ABC transporters. Here, we investigated the effect of si...

Background PD is a progressive neurodegenerative disorder commonly treated by levodopa. The findings from genetic studies on adverse effects (ADRs) and levodopa efficacy are mostly inconclusive. Here, we aim to identify predictive genetic biomarkers for levodopa response (LR) and determine common molecular link with disease susceptibility. A system...

Background As variability in the clinical profile of dementia subtypes had been reported with regional differences across the world, we conducted a retrospective hospital-based study in a North Indian population. Methods We retrieved patient records from 2007 to 2014 for details of clinical evaluation, diagnosis, neuroimaging, biochemical investig...

Purpose: Over expression of ATP-binding cassette transporters is considered one of the major reasons for non-responsiveness to antiepileptic drugs. Carbamazepine (CBZ), one of first line antiepileptic drug is known to influence ABCC2 expression but its exact molecular mechanism is unknown. Methods: We investigated the effect of CBZ on expression...

A huge number of G-rich sequences forming quadruplexes are found in human genome, especially on telomeric regions, UTR’s, and promoter regions of a number of genes. One such gene is GRIN1 encoded by NR1 subunit of N-methyl-D-aspartate receptor (NMDA). Several lines of reports have implicated that attenuated function of NMDA results in schizophrenia...

Background: Alzheimer disease (AD) is a progressive neurodegenerative disease with a complex multifactorial etiology. Here, we aim to identify a biomarker pool comprised of genetic variants and blood biomarkers as predictor of AD risk. Methods: We performed a case-control study involving 108 cases and 159 non-demented healthy controls to examine...

In the last century, advances in biomedical sciences led to improvements in quality of human life mainly by decreasing the disease burden and providing various healthcare innovations. Effective medications were developed for most infectious diseases, lifestyle disorders, and other diseases. For once, we all believed that we can create a disease-fre...

Epilepsy is a neurological disorder affecting around 1%-2% of population worldwide and its treatment includes use of antiepileptic drugs to control seizures. Failure to respond to antiepileptic drug therapy is a major clinical problem and over expression of ATP-binding cassette transporters is considered one of the major reasons for pharmacoresista...

Pathogenic expansion of a hexanucleotide repeat in C9orf72 is associated with ~ 30% of familial ALS and ~ 7% of sporadic ALS patients amongst different populations. This repeat expansion was screened in 75 ALS patients and 115 healthy individuals from North India. On analysis by repeat-primed PCR, pathogenic expansion was not observed either in ALS...

Animal experiments that are conducted worldwide contribute to significant findings and breakthroughs in the understanding of the underlying mechanisms of various diseases, bringing up appropriate clinical interventions. However, their predictive value is often low, leading to translational failure. Problems like translational failure of animal stud...

Background: Genetic differences in the target proteins, metabolizing enzymes and transporters that contribute to inter-individual differences in drug response are not integrated in contemporary drug development programs. Ayurveda, that has propelled many drug discovery programs albeit for the search of new chemical entities incorporates inter-indiv...

BACKGROUND: Genetic differences in the target proteins, metabolizing enzymes and transporters that contribute to inter-individual differences in drug response are not integrated in contemporary drug development programs. Ayurveda, that has propelled many drug discovery programs albeit for the search of new chemical entities incorporates inter-indiv...

Background: Genetic differences in the target proteins, metabolizing enzymes and transporters that contribute to inter-individual differences in drug response are not integrated in contemporary drug development programs. Ayurveda, that has propelled many drug discovery programs albeit for the search of new chemical entities incorporates inter-indiv...

Background: Genetic differences in the target proteins, metabolizing enzymes and transporters that contribute to inter-individual differences in drug response are not integrated in contemporary drug development programs. Ayurveda, that has propelled many drug discovery programs albeit for the search of new chemical entities incorporates inter-indiv...

Background: Genetic differences in the target proteins, metabolizing enzymes and transporters that contribute to inter-individual differences in drug response are not integrated in contemporary drug development programs. Ayurveda, that has propelled many drug discovery programs albeit for the search of new chemical entities incorporates inter-indiv...

Background: Genetic differences in the target proteins, metabolizing enzymes and transporters that contribute to inter-individual differences in drug response are not integrated in contemporary drug development programs. Ayurveda, that has propelled many drug discovery programs albeit for the search of new chemical entities incorporates inter-indiv...

Background: Genetic differences in the target proteins, metabolizing enzymes and transporters that contribute to inter-individual differences in drug response are not integrated in contemporary drug development programs. Ayurveda, that has propelled many drug discovery programs albeit for the search of new chemical entities incorporates inter-indi...

Table S1. Gene‐wise summarized status of SNPs for final genotype‐phenotype correlation. Table S2. Association of variants in all epilepsy patients and seizure type subgroups. Table S3. Association of variants in all epilepsy patients and epilepsy type subgroups. Table S4. Gene‐gene interaction results for best models among SVC and ion channel ge...

"Common epilepsies", merely explored for genetics are the most frequent, nonfamilial, sporadic cases in hospitals. Because of their much debated molecular pathology, there is a need to focus on other neuronal pathways including the existing ion channels. Methods: For this study, a total of 214 epilepsy cases of North Indian ethnicity comprising 59....

Aim: The present study aimed to evaluate association of genetic variants on drug response and therapy optimization parameters in patients treated with first-line antiepileptic drugs (AEDs). Genetic variants from ion channels, their functionally related genes, and synaptic vesicle cycle (SVC) genes with a potential role in epilepsy pathophysiology...

Introduction “Common epilepsies”, merely explored for genetics are the most frequent, nonfamilial, sporadic cases in hospitals. Because of their much debated molecular pathology, there is a need to focus on other neuronal pathways including the existing ion channels. Methods For this study, a total of 214 epilepsy cases of North Indian ethnicity c...

Background: The catechol-O-methyltransferase (COMT) enzyme plays a crucial role in dopamine degradation, and the COMT Val158Met polymorphism (rs4680) is associated with significant differences in enzymatic activity and consequently dopamine concentrations in the prefrontal cortex. Multiple studies have analyzed the COMT Val158Met variant in relatio...

CYP1A1 gene is involved in estrogen metabolism, and previously, we have reported association of variant rs2606345 with altered anti-epileptic drugs (AED) response in North Indian women with epilepsy (WWE). The present study aims to replicate the pharmacogenetic association, perform functional characterization and study its distribution within ethni...

Mutations in the superoxide dismutase (SOD1) gene account for ∼15% and in the transactive response DNA binding protein (TARDBP) gene for ∼5% of familial amyotrophic lateral sclerosis (FALS) cases. These two genes were analysed in two siblings from North India with ALS and a positive family history. The coding region of SOD1 and TARDBP genes was seq...

The possible association between Apolipoprotein E (ApoE) levels in the cerebrospinal fluid (CSF) and Alzheimer's disease (AD) has been studied extensively. However, previous findings have been inconsistent. We conducted a meta-analysis of observational studies, seeking to provide insights into ApoE's potential as a biomarker for AD. A systematic li...

Background: Leptin, a 16 kDa peptide hormone synthesized and secreted specifically from white adipose cells protects neurons against amyloid β-induced toxicity, by increasing Apolipoprotein E (APO E)-dependent uptake of β amyloid into the cells, thereby, protect individuals from developing Alzheimer's disease (AD). The APO E ε4 allele is a known g...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and other cognitive functions. AD can be classified into familial AD (FAD) and sporadic AD (SAD) based on heritability and into early onset AD (EOAD) and late onset AD (LOAD) based on age of onset. LOAD cases are more prevalent with genetically comp...

Table S2. In silico functional analysis of associated SNP in antipsychotic treatment.

Table S1. Chlorpromazine (100 mg/day) equivalent doses for antipsychotics prescribed in present study.

Neurodevelopmental and neuroimmunological genes critically regulate antipsychotic treatment outcome. We report genetic associations of antipsychotic response in 742 schizophrenia patients from Indian populations of Indo-European and Dravidian ancestry, segregated by disease severity. Meta-analysis comparing the two populations identified CCL2 [rs47...

Genetic factors have potential of predicting response to antidepressants in patients with major depressive disorder (MDD). In this study, an attempt was made to find an association between response to escitalopram in patients with MDD, and serotonin transporter (SLC6A4) and receptor (5HTR1A, 5HTR2A) polymorphisms. Fifty five patients diagnosed as s...

Genetic studies pertaining to effector molecules have been pivotal in schizophrenia research. The serotonin receptor HTR3A is an effector that plays a key role in schizophrenia development. Previously, we identified a promoter variant of HTR3A, rs1062613, to be associated with the disease in the Indian population. The present study was undertaken t...

The renin-angiotensin system (RAS) genes polymorphism have been associated with blood pressure (BP) response to antihypertensives drugs and may also influence the variability in visit-to-visit BP. Here we have investigated the association of RAS gene polymorphism with response to three classes of antihypertensive drugs (atenolol, amlodipine and ena...

Context: Phenytoin (PHT) is one of the frontrunner drugs used as monotherapy in the management of epilepsy. It is also one of the most common drugs causing adverse drug reactions (ADRs). The aim of this study was to study the relationship between serum PHT levels and the age, gender, dosage and genetic polymorphisms in a North Indian population. Th...

I Introduction Patients with chronic schizophrenia require long term treatment. Attitude towards antipsychotic medications is a crucial determinant of medication adherence and is influenced by multiple factors. The present study was conducted to investigate clinical and socio-demographic correlates of attitude of patients with schizophrenia to the...