Current Work Profile

SARS-CoV-2 and Post COVID-19 complications

SARS-CoV-2, an enveloped positive-sense RNA virus from the Coronaviridae family and Betacoronavirus genus, has caused one of the deadliest pandemics in human history, COVID-19. By October 2023, around 700 million cases and 70 million deaths had been reported globally, with India accounting for 45 million cases and 5 million deaths. SARS-CoV-2, one of the largest known RNA viruses with a ~30kB genome, encodes structural proteins (Spike, Envelope, Membrane, and Nucleocapsid) and nonstructural proteins (NSP1-10 and NSP12-16), along with nine accessory proteins. The Spike protein, in particular, has undergone numerous mutations, increasing the virus's pathogenicity and infectivity, leading to the emergence of multiple variants of concern (VOCs).

Our research focuses on understanding the molecular signatures of these VOCs to elucidate the variations in infectivity and severity. We also investigate how co-infections and comorbidities, such as hypertension, cardiovascular diseases, diabetes, and cancer, exacerbate COVID-19 severity. Cancer patients, often immunocompromised, exhibit higher mortality rates and more severe multi-organ dysfunction when infected with SARS-CoV-2.

COVID-19 predominantly manifests through respiratory symptoms, but neurological complications such as Guillain-Barré syndrome, headaches, seizures, and meningitis are also observed. The severity of respiratory issues varies, with some patients developing acute respiratory distress syndrome (ARDS). Host immune responses play a dual role, both combating the virus and contributing to COVID-19 pneumonia via cytokine release. Disruption of the lung-brain axis is increasingly recognized, with severe respiratory distress contributing to neurological impacts such as cognitive impairment and neurological sequelae.

Accurate diagnosis and severity assessment are crucial. While qRT-PCR remains the gold standard for detection, chest CT scans provide critical insights into disease progression. Our lab explores how disruptions in the lung-brain axis contribute to neurological complications, aiming to develop targeted interventions to mitigate these adverse outcomes.

Epstein-Barr Virus and Helicobacter pylori coinfection in Gastric cancer

Gastric cancer remains one of the most common cancers worldwide. Generally, GC is viewed as the consequence of a multifactorial process, involving the host responses, bacterial virulence, diet, and other environmental factors Helicobacter pylori and Epstein Barr virus are two such pathogenic agents causes gastric cancer. H. pylori is commonly found and around 80% of the world population would show positive for the bacterium. GC development is a multistep process initiated by the transition of normal mucosa to chronic superficial gastritis (non-atrophic gastritis), triggered primarily by H. pylori infection. EBV associated gastric cancer comprises of 10% of gastric cancer, Generally, it is harmless and stays in the latent state inside the body. But in an opportunistic condition, it may cause several types of cancer and other conditions. We recently investigated the co-infection scenario with both the pathogens and how they help each other in aggressiveness of the disease. The figure explains the outline of our work in different domains. We are working on the clinical isolates of the bacterium. H. pylori is known to disturb the cell polarity, but how the coinfection scenario changes the status is under investigation. Further the expression and activity of receptor tyrosine kinase (ITK & FYN), serine/threonine kinase (AURKA) and gankyrin the oncogenic proteins also gets modulated upon infection is under examination.

Bacterial- Viral pathogenic synergy in Neurodegeneration

Dr. Hem Chandra Jha and his colleagues at Univ. of Pennsylvania, demonstrated in-vitro EBV infection of neurons for the first time. This work instigated the curiosity in him to explore the domain of neurovirology as a principle investigator at IIT Indore. The IBEG neurovirology team investigated various aspects in this regard like the research of nuances in glial cells (astroglia & microglia) post EBV infection using Raman spectroscopy. The study revealed signature biomolecular changes happening in the host cell upon EBV infection. Further we explored changes occurring in astroglial cells upon direct and indirect EBV infection through EBV infected peripheral blood mononuclear cells. In this study, we observed the possibility that EBV may aid in generating neuroinflammatory reactions. Moreover, our in-silico studies revealed plausible phytochemicals candidates as anti-viral agents as virus-specific therapeutics. In continuation of these studies we are currently looking into various aspects of glial cell mediated neuroinflammation as a cause of neurodegenerative effect.

Gut-Brain axis: Antimicrobial resistance and Neurodegeneration

The gut-brain axis constitutes a sophisticated bidirectional communication network between the gastrointestinal tract and the brain, intricately involved in the regulation of physiological processes such as immune responses, neurotransmitter signaling, and homeostasis. Emerging research highlights the pivotal role of this axis in maintaining neurological health, as it facilitates intricate interactions between microbial metabolites and neural pathways. Our research delves into the mechanisms by which pathogenic microorganisms breach the intestinal barrier, exploiting the gut-brain axis to infiltrate the central nervous system (CNS). Once within the CNS, these pathogens can trigger a cascade of neuroinflammatory responses, potentially leading to severe neurological complications. Of particular interest is the association between gut-derived pathogens and neuronal memory loss, a symptom frequently observed in neurodegenerative disorders. By utilizing advanced molecular techniques and in vivo models, we aim to elucidate the pathways through which these pathogens impact neuronal integrity and cognitive function. This understanding of pathogen-mediated neurodegeneration could pave the way for novel therapeutic interventions.

Identification of Biomarkers in Oral Cancer

The habitual consumption of areca nuts in India and Southeast Asia has been associated with oral submucous fibrosis (OSMF) and its malignant transformation into oral squamous cell carcinoma (OSCC). The early diagnosis of OSCC poses a challenge in the clinical setup. The lesion biopsy remains the gold standard for detecting oral cancer but has disadvantages like scar formation and a further reduction in mouth opening. Moreover, the biopsy is invasive and cannot be performed repeatedly. There is a need to develop non-invasive methods for the early diagnosis of malignant transformation of OSMF. Our group aims to identify the unique biomarkers that are altered in the early stages of malignant transformation of OSMF compared to healthy and OSMF tissues. We also aim to establish an in vitro model to study the effects of areca nut, tobacco and lime on progression of OSCC.

The work includes observational cross-sectional clinical studies and in vitro experiments. Saliva and lesion tissue scrapings were collected from OSMF, OSCC, and Healthy subjects. Total metabolites and lipids were isolated from saliva, and LCMS was performed for metabolomics and lipidomics. RNA was isolated from tissue scrapings, and an mRNA expression profile for OSCC-related genes was performed. Total proteins were isolated from lesion scrapings for proteomic analysis. Biomarker analysis was performed using dimensionality reduction (PLS-DA), and the area under the curve for the metabolites and proteins was studied. Pathway enrichment analysis was also performed to identify the most altered pathways in OSMF and OSCC.

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