Molecular And Cellular Medicine

• Mechanisms of Immune shift in Acute Liver failure and Acute on Chronic Liver Failures
• Resistance mechanism of Hepatocellular Carcinoma
• Mechanisms of immune paresis and sepsis in liver failure
• Regenerative Medicine and Genome Editing
• Hepatomics : Microbiome, Metagenome, Metabolome and Epigenome
• Extracellular vesicles in liver disease
• Animal physiology
• Vascular biology and portal hypertension
• Developing animal models of liver disease

National Recognitions

• BIRAC Funded program for establishing preclinical models for Drug discovery
• DST funded core Laboratory for Non-Transplant Therapeutic Strategies for Advanced Liver Disease.
• ILBS-Ayush Project on Pre-clinical Trials of Ayur Formulations for Fatty Liver Disorder
• Indo-French Node, 'InFLeMin', supported by the CEFIPRA/DST and INSERM, France
• ICMR-approved Centre for Advanced Research on Bioengineered In-vitroLiver Models for Evaluation of Hepatotropic Infectionsand Therapeutics: In collaboration with IIT-Guwahati

Highlights of the Research Activities

(Dr. Nirupma Trehanpati, Hepato Immunology Lab)
scRNA-Seq Reveals Sustained Pro-Inflammation by Innate Immune Activation in In Utero HBV-Exposed Neonates of High HBsAg Mothers (Pahwa et al. 2025, Liver International)

Dr Trehanpati's group is focused in viral hepatitis, especially in HBV vertical transmission and fulminant hepatitis in HEV pregnant women. We performed a comprehensive analysis of immune responses before and after HBV vaccination in infants born to mothers with high and low viral load and HBsAg levels. Single-cell RNA sequencing (scRNA-seq) and immunophenotyping allowed us to directly characterise the impact of HBV exposure on the newborn immune status, pre-and post-HBV vaccination. Neonates exposed to high viral load showed increased exhaustion markers and reduced metabolic activity in CD8+T cells at pre-and post-HV vaccination.

ScRNA-seq Identifies High CXCL8 Linked to Liver Fibrosis in HBeAg Negative Chronic Hepatitis B Patients with Low HBsAg ( Singh et al. Gastro Hep Advances, 2025)
Unravelling the molecular pathogenesis of gallstone-associated disease (Dr Gayatri Ramakrishna, BiochemBiophys Res Communication)

India has a high incidence of gallstone disease, which leads to chronic inflammation of the gallbladder and substantially increases the risk of gallbladder cancer. Owing to its aggressive biology and late clinical presentation, gallbladder cancer is associated with a dismal prognosis. In this context, we recently initiated two major lines of investigation in gallstone-associated disease:

(a) delineating the dynamics of gallstone formation, including growth kinetics, dormancy patterns, and compositional heterogeneity, and (b) characterising the evolutionary trajectory of gallbladder cancer to better understand tumour initiation and progression. Our pilot findings using the bomb pulse method of 14C dating suggest that a minimum of 6 years is required for complete gallstone formation and remain dormant for further 4-18 years. Using 16S rRNA, we report the presence of pathogenic species of Klebsiella and E coli in the gallstone core, which was rich in oxalate (Yadav et al, J GastrointestSurg, 2025). We successfully established a patient-derived xenograft model of gallbladder adenosquamous carcinoma, with KRAS (G12V) identified as a potential initiating mutation, and the probable tumour-initiating cell is derived from an EpCAM-positive putative cancer stem cell. Sequential analysis revealed the emergence of resistant clones and adaptive selection of chromatin remodelers (ARID) in the PDX model (Yadav et al , Dig Dis Sci, 2025). In parallel, we proposed the Hepatocyte Red Queen Effect, describing adaptive strategies that confer hepatic resilience to ageing (Chatterjee et al., Ann Hepatol, 2024).

Protein supplementation differentially alters gut microbiota and associated liver injury recovery in mouse model of alcohol-related liver disease (PI: Dr. Shevtank, Clin Nutr.)

The work of the group spans a broad spectrum of cutting-edge biomedical topics, emphasizing the intricate interplay between host metabolism, microbiota, and molecular pathogenesis in liver diseases and systemic inflammatory disorders.With a strong background in integrated analytical methods including computational biology we continue to influence clinical protocols and inspires new investigations into the intricate mechanisms of liver health and disease.Patients with Alcohol-related Liver Disease (ALD) are advised increased protein supplementation. A recent study from the group evaluated the effects of protein supplementation from two sources, soya (veg) or egg, on gut microbiota modulation and ALD remission.Veg-diet decreased hepatic steatosis and fibrosis compared with std diet. ALT and AST levels reduced by 40 % and occludinby 80 %, compared to egg-diet. Plasma endotoxin levels in veg were reduced by 64 % and 32 % compared to stdor egg diet.Veg-diet increased beneficial taxa, Lachnospiraceae UCG-006, Prevotellaceae NK3B31, while decreasing pathogenic Roseburia, Klebsiella, Staphylococcus etc. Thus, alteration in protein alone can affect variable outcomes in ALD, with protein from vegetable sources resulting in enhanced improvement in the gut-liver axis. Vegetable protein-supplemented diet enhances fatty acid beta oxidation and energy metabolism accompanied by improvement in gut-dysbiosis and ALD associated hepatic injury.

Liver Macrophage Dysfunction as a Central Driver of Regeneration Failure in ACLF (Nat Rev Gastroenterol Hepatol., Dr Anupam Kumar)

Liver regeneration after parenchymal injury is initiated by bone-marrow derived macrophages (BMDMs), which clear necrotic tissue and orchestrate hepatocyte proliferation through trophic growth-factor signalling(figure -X). In acute-on-chronic liver failure (ACLF), however, monocytes and macrophages undergo profound bioenergetic failure, leading to accumulation of metabolically exhausted and immunoparalyzed macrophages with defective phagocytosis, impaired efferocytosis, and blunted regenerative signalling.

As a result, compensatory hepatocyte proliferation becomes ineffective despite ongoing tissue injury. This macrophage dysfunction is further reinforced by depletion of bone-marrow stem cell reserves and a shift from pro-regenerative IL-6/STAT3 to anti-regenerative IFN- /STAT1 signaling. Restoring macrophage bioenergetics and function such as through umbilical cord derived mesenchymal stromal cell therapy has been shown to reprogram pathogenic myelopoiesis, enhance hepatic repair, and improve liver regeneration in experimental ACLF.( Sarin SK, Choudhury A, Kumar A et al ; Acute-on-chronic liver failure: pathophysiological mechanisms and clinical management. Nat Rev Gastroenterol Hepatol. 2026 PMID:

41486194). Figure: Steps in liver regeneration and dysregulation of these steps inacute-on-chronic liver failure.

Hepatitis B Virus x Protein Increases Cellular OCT3/4 and MYC and Facilitates Cellular Reprogramming (Dr Sanal MG)

Hepatitis B virus x (HBx) is a multifunctional protein coded by the Hepatitis B virus that is involved in various cellular processes such as proliferation, cell survival/apoptosis, and histone methylation. HBx was reported to be associated with liver "cancer stem cells." The stemness inducing properties of HBx could also facilitate the generation of pluripotent stem cells from somatic cells. It is well established that somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) using a cocktail of transcription factors called Yamanaka's factors (YFs) (OCT4, SOX2, KLF4, and MYC). The reprogramming process proceeds step-by-step with reprogramming factor chromatin interactions, transcription, and chromatin states changing during transitions. HBx is a "broad spectrum trans-activator" and therefore could facilitate these transitions. Our work showed that we found that the addition of HBx to YF improves iPSC derivation, and it increases the efficiency of iPSC generation from "difficult or hard-to-reprogram samples" such as high passage/senescent fibroblasts. To conclude, HBx improves the reprogramming efficiency of YFs. HBx increases the cellular levels of OCT3/4 and MYC.

Liver Vascular Biology Lab: Lithocholic acid facilitates release of angiocrine factors by liver sinusoidal endothelial cells during liver regeneration.(PI: Dr Savneet Kaur, Npj Gut and Liver)

Dr Savneet's lab focusses on mechanisms underlying liver regeneration and diseases, focussing on vascular niche. Her team has contributed immensely in understanding the role of lymphatic vessels in liver cirrhosis. Recently, her team investigated bile acid (BA) composition in liver regeneration using two-thirds partial hepatectomy (PHx) rat models and human donors undergoing hepatectomy by mass spectrometry. We studied the effects of differentially expressed BA on LSECs in several in vitro and in vivo experiments. Results revealed that secondary BA were significantly increased in the peripheral serum of both PHx models and human donors at day 2 post-PHx compared to controls. In vitro, lithocholic acid (LCA) enhanced the expression of endothelial cell-specific transcription factor, Id1, along with angiocrine factors, HGF and Wnt2 in LSECs. LSECs treated with TGR5-siRNA in vitro and from in vivo antibiotic-treated PHx animals showed decreased expression of Id1 and angiocrine factors. The study unveils that LCA drives Id1-TGR5 angiocrine pathway and activates the release of Wnt2 and HGF in LSECs, facilitating early liver regeneration. Further studies are underway to study liver lymphatic vessels in regeneration.

Laboratory of Extracellular Vesicles: Small Size but Big Impact in Liver Diseases (Dr. Sukriti Baweja)

The laboratory of Sukriti Baweja focuses on translational research in immune-mediated and metabolic liver diseases, with particular emphasis on extracellular vesicle (EV) biology as a driver of liver inflammation and immune dysregulation. In the realm of biomedical research, our laboratory of extracellular vesicles (EVs) stands at the forefront, unravelling the intricacies of cell-to-cell communication. Specializing in the study of nanoscale membrane-bound structures released by every cell type, known as extracellular vesicles, this cutting-edge facility employs advanced techniques to decipher their role specially in liver disease. The EV are being isolated not only from host cells but also from bacteria, virus and plantkingdom to be utilised in developing novel diagnostics and therapies. During 2025, a major research focus was the investigation of bacterial extracellular vesicles (BEVs) and their role in the pathogenesis of autoimmune hepatitis (AIH). The lab examined the immunomodulatory properties of gut-derived BEVs and their impact on hepatic immune activation, antigen presentation, and loss of immune tolerance. Ongoing work includes molecular characterization of BEVs, assessment of their interaction with hepatic immune cells, and evaluation of their potential as diagnostic and prognostic biomarkers in AIH.
Collectively, the laboratory's work aims to advance mechanistic understanding of host microbe communication in immune-mediated liver diseases and to translate EV-based discoveries toward clinical applications.

Figure 1: Patients with Autoimmune Hepatitis (AIH) exhibited elevated levels of circulating and fecal bacterial extracellular vesicles (BEVs), enriched with virulence-associated proteins. The circulating BEVs were distinct from those found in healthy and other liver diseases, suggesting their potential as non-invasive biomarkers. The findings highlight a novel mechanistic role of BEVs in contributing to immune activation and liver injury in AIH, offering insights for future diagnostic and therapeutic strategies.

Circulating urobilinogen augments inflammation and corticosteroid non-response in severe alcohol-induced hepatitis (Mol Ther, Dr. Jaswinder Maras)

ILBS has a state-of-the-art Multi-Omics Lab, where cutting-edge research meets advanced technology to unravel the complexities of liver diseases. Our multi-omics lab specializes in proteomics, metabolomics, lipidomics, and meta-proteomics, enabling a comprehensive understanding of liver diseases at molecular and functional levels.We are equipped with 2 high-resolution mass spectrometry (HRMS) Q exactive plus and an array of advanced analytical tools, we deliver precise and in-depth profiling of proteins, metabolites, lipids, and microbial protein communities. This multi-disciplinary approach empowers us to explore diverse biological questions, identify biomarkers, and understand disease mechanisms with unmatched accuracy and high impact publications. In a recent study, our research identifies plasma urobilinogen as a critical biomarker for predicting which patients with severe alcohol-associated hepatitis will fail to respond to standard steroid therapy. Using metabolomics and machine learning, researchers found that non-responders exhibit distinct metabolic inactivity and a lack of gut bacterial diversity. Elevated urobilinogen levels (above 0.07 mg/mL) were found to trigger inflammation and steroid resistance by increasing glucocorticoid receptor expression. The study also demonstrated that fecal microbiota transplantation could lower these toxic levels by restructuring the gut microbiome. Ultimately, measuring urobilinogen provides a highly accurate tool for predicting early mortality and suggests that targeting the gut-liver axis could improve patient survival.

Targeting Glycolytic Rewiring Rescues Liver sinusoidal endothelial cells Mitochondrial Bioenergetics and Vascular Barrier Integrity mitigates endotoxin mediated Portal Hypertension in Cirrhosis (Dr. Dinesh Mani Tripathi)

Dr. Dinesh Mani Tripathi is specialized in the areas of Portal hypertension and Liver cirrhosis associated Hepatic vascular disorders aligned with Drug discovery and development platform. His team focuses on in-depth investigation in the mechanobiology of liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs) and extracellular matrix remodelling, Development of liver-on-chip platforms to study novel therapeutic targets with core involvement of tissue engineering aspects. The group also aims to study metabolic reprogramming due to sepsis in cirrhosis and its roles in hepatic microvascular dysfunction. In cholestasis liver, the aim is to study the cellular cross-talk of bile duct epithelial cells in regeneration and fibrosis and develop the anti-fibrotic therapeutic targets. Additionally, bile fluid mechanics and hepatocyte dynamics under cholestatic conditions are investigated to uncover alternative therapeutics.

Center for Comparative Medicine

The Center for Comparative Medicine (CCM) within the Department of Molecular and Cellular Medicine at the Institute of Liver and Biliary Sciences (ILBS) serves as a vital platform for advancing hepatobiliary research through comprehensive in vivo experimentation while upholding the highest standards of ethical and humane animal care.CCM is registered with CCSEA (No. 1562/GO/ReRcBiBt/S/11/CCSEA; valid till 21/09/2028) and authorized for educational and commercial research, in-house breeding, and trading of small laboratory animals. Spread over ~15,000 sq. ft., the facility houses modern infrastructure for animal housing, breeding, and experimentation, supported by skilled veterinarians and trained technical staff. All research protocols involving animals are evaluated and approved by the Institutional Animal Ethics Committee (IAEC), which includes both internal members and external nominees from CCSEA, and the committee actively monitors compliance with animal welfare standards. CCM plays a key role in developing small animal models of human liver diseases and contributes to capacity building through training programs and hands-on workshops in laboratory animal biomethodology, welfare, ethics, handling, and rodent surgery for internal PhD scholars and external researchers. The center supports advanced comparative medicine research using diverse models, including mice (C57BL/6J, C57BL/6N, BALB/c, B6.GFP, and Athymic CD-1 nude), rats (Sprague Dawley and Long Evans), zebrafish, and New Zealand White rabbits, with the overarching aim of enhancing health outcomes for both humans and animals.

Key Achievements and Activities of CCM–ILBS in 2025

• Maintained full compliance with CCSEA guidelines under IAEC oversight.
• IAEC reviewed and approved 31 research proposals during 2025.
• Conducted the Laboratory Animal Bio methodology, Welfare, and Ethics program in Jan and July 2025, training 05 PhD scholars.
• Held the 7th Certificate Course in Laboratory Animal Handling & Experimentation from December 10-13, 2025, with 19 participants.
• Organized 3rdRodent Surgery Workshop (RS101) from April 3-5, 2025, with 21 participants.
• Established advanced animal models of liver disease, including Pregnancy Associated Diabetes/MASLD, Hepatoencephalopathy(HE), gallstone disease, vagotomy-induced injury, CBDL-induced HPS, partial hepatectomy (mice and rats), PPVL-induced non-cirrhotic portal hypertension, and multiple HCC mouse models (xenograft, orthotopic, syngeneic, DEN-induced).
• Dr. Anupma Kumari received the prestigious ICLAS AFLAS Youth Progress Award, at the 10th AFLAS Congress & 18th Academic Conference on Laboratory Animal Science and Technology of China, held in Hangzhou, China, from 21-24 October 2025, hnology and the Scientific Advisory Committee, PMO.

CCM–ILBS Team

Dr. Savneet Kaur - Associate Professor & Scientist In-Charge
Dr. K. B. Patel - Chief Veterinary Officer
Dr. Anupma Kumari - Veterinary Officer
Mr. Karmjeet, Mr. Abhay Singh, Mr. Satendra Kumar, Mr. Akhilesh Yadav - Junior Animal Technicians

Confocal Microscopy Facility

The Confocal Microscope Facility at ILBS is a state-of-the-art cellular imaging facility, generously supported under the FIST programme of the Department of Science and Technology (DST-FIST), Ministry of Science and Technology, Government of India. The confocal microscope is a versatile imaging platform for biological research specimens, including 2D cell cultures, 3D spheroids, and paraffin-embedded tissue specimens.

Services Provided

The confocal microscopy facility provides researchers with the capability to visualize a wide range of samples using both fixed and live-cell imaging approaches. Cell cultures in 2D and 3D formats, as well as embryos, can be effectively imaged. Advanced quantitative imaging techniques such as FRAP, FLIP, and FRET are available. The laboratory also maintains several dedicated workstations equipped with software packages for image processing, analysis, and 3D image reconstruction. The imaging facility enables scientists to use high-end instrumentation for image acquisition, along with the training and technical support required for accurate interpretation of microscopic images. As a national facility, it is open to investigators from ILBS as well as the wider research community within Delhi and across India. The facility also provides hands-on training to students.

Key Features of Instrumentation:

• Model: Leica SP8
• Point Scanning with 04 Excitation lasers ( Diode 405nm, Argon Line :458nm, 488nm, 514nm, DPSS 561nm, HeNe 633nm)
• Spectral Detection: 3PMTs and 2 HyDs( ultrasensitive detectors)
• Objectives: Dry objectives: 10X, 20X, 40X, Oil Immersion: 63X and 100X.
• Multi-dimensional acquisition for time series, z stack and lambda scan

Team : Prof. Nirupma Trehanpati (Faculty in-charge, MCM)
Prof. Gayatri Ramakrishna (Coordinator)
Technical Staff: Dileep, Arun, Surinder

Biosafety Level-3 Containment Facility

The Biosafety Level-3 (BSL-3) facility at the Institute of Liver and Biliary Sciences (ILBS), housed within the Department of Molecular and Cellular Medicine, was established in 2018 and became operational in May 2019. The facility operates under the regulatory oversight of the Review Committee on Genetic Manipulation (RCGM) and the Institutional Biosafety Committee (IBSC) and is certified by the RCGM (Certificate No. BT/IBKP/070/2020-BSL3). All activities are conducted in accordance with approved Standard Operating Procedures (SOPs), and the Manual: Practices and Procedures for Working in BSL-3 Laboratories.

The BSL-3 laboratory operates under stringent biosafety and biosecurity controls in compliance with the National Guidelines for the Establishment and Certification of Biosafety Level-3 (BSL-3) Containment Facility, 2024. Access is restricted to trained and authorized personnel, with a comprehensive user training program conducted in August 2025. As part of a skill-building initiative, the 1st Workshop on BSL-3 Laboratory Practices and Hands-on Training for external researchers was organized on 17 June 2025. During 2025, the facility was primarily utilized by the Department of Virology for SARS-CoV-2 diagnostic testing, supported by negative-pressure containment, routine audits, and continuous monitoring.

The facility supports both in vitro and mouse experimentation and is equipped with robust core infrastructure, including uninterrupted power supply, emergency shutdown systems, standby air-handling units, and fumigation capabilities. Key equipment comprises Class II biosafety cabinets, deep freezers, CO incubators, centrifuges, inverted microscopes, individually ventilated cages, an isoflurane anesthesia system, and a double-door autoclave, ensuring safe and sustained high-containment operations.

Team : Prof. NirupmaTrehanpati (HOD, Department of MCM)
Prof. Gayatri Ramakrishna (Scientist In-Charge, BSL-3)
Dr. KB Patel (BSL-3 Biosafety Officer)
ILBS Engineering Staff and Biosafe Engineers

cGMP Facility

Emerging science of cell and gene therapy like stem cell therapy, immune cell therapy and hepatocyte transplant holds great promise in the management of liver patients. However, their usages in India are limited due to required infrastructure and expertise. To promote the use of these therapies for the benefit of patients with liver failure and HCC, ILBS had developed an state-of-the-art Therapeutic Cells Production (cGMP) Facility. The facility has approximately 200 Sqr. meter ISO Class-6 clean room with 2 production suits, one media preparation suit, one pre-processing, one analysis suit and one Cryostorage suit fully equipped with GMP compliance Cell therapy system (CTS). At present the facility is actively involved in production of clinical grade umbilical cord mesenchymal stem cells for the treatment of patients with liver failure. On compassionate ground these cells have been used in some steroid non-responsive/ineligible alcoholic hepatitis patients having no transplant option and shown encouraging response.

Team : Dr. Anupam Kumar (Faculty in-charge)
Mr. Satish (Technical Officer)

Courses offered

Department's Achievements

• The department successfully launched the Indo-French Node, 'InFLeMin', supported by the CEFIPRA/DST and INSERM, France a virtual university, scaling joint Indo-French collaborations.
• The department has received extramural fundings form national agencies for conducting focused research in areas of molecular medicine. DBT (3 : total 3.1 cr), DST (1 : total 30 lakh), SERB (3: total 1cr), Ayush (2: total 2 Cr), ICMR (11: total 9.5Cr), CEFIPRA (1: total 1.5cr) BVG Lifesciences(1: 35 Lakh)
• Students have presented their ongoing work in the prestigious national and international conferences like AASLD (6) , EASL (5) , ISGCON (3), APDW (3)
• NAMS Fellowship awarded to Dr. Nirupma Trehanapati and Dr. Savneet Kaur, 2025.
• The students have bagged travel grants, bursaries, and best presentation awards in National and International meetings.
• Nine students awarded PhD Degree in Biomedical Sciences.
• The department also successfully conducted several workshop and training programmes.