Stanford Advisors


All Publications


  • BRCA1/2-stratified immune profiling of treatment-naive high-grade serous ovarian cancer ascites identifies a Treg-enriched ascitic immune phenotype. Journal of pathology and translational medicine Sharma, M., Kaur, B., Rai, B., Sachdeva, M. U., Sharma, A. R., Gupta, P., Gautam, U., Bagga, R., Srinivasan, R. 2026

    Abstract

    Background: Malignant ascites is a common presentation in advanced high-grade serous ovarian carcinoma (HGSOC), yet its immune composition and genetic correlates remain poorly defined. This study explored the immune microenvironment of ascitic fluid in ovarian carcinoma and its association with BRCA mutation status, chemotherapy response, and survival.Methods: Ascitic fluid from 133 patients (33 non-malignant controls, 31 non-ovarian carcinoma, and 69 HGSOC cases) was analyzed using multiparameter flow cytometry to quantify lymphocyte and macrophage subsets, and programmed cell death 1/programmed cell death ligand 1 immune-checkpoint marker expression. Targeted sequencing of TP53 and BRCA1/2 was performed in HGSOC, and findings were correlated to immune parameters, chemotherapy response, progression-free and overall survival.Results: Ovarian carcinoma ascites, compared with non-malignant effusions, showed increased CD3+ and CD8+ T-cell frequencies, higher regulatory T cell (Treg)-associated populations, and reduced CD19+CD20+ B-cell levels. Targeted sequencing identified TP53 mutations in 97.4% and BRCA1/2 mutations in 35.9% of sequenced HGSOC cases. BRCA-wild-type cases showed significantly lower CD4+ T-cell and B-cell levels, higher Treg levels, and shorter progression-free and overall survival than BRCA1/2-mutated cases. Higher CD3+ and CD8+ T-cell levels were associated with poor chemotherapy response. In exploratory multivariable Cox models, BRCA-wild-type status remained significantly associated with poorer overall survival, whereas immune-cell groups were not independently significant.Conclusions: HGSOC ascites showed a Treg-enriched immune profile, with relatively higher Treg levels in BRCA-wild-type cases. BRCA-wild-type status was associated with poorer outcomes, while the evaluated immune-cell subsets were not independently prognostic in exploratory analysis. Ascitic fluid-based immune and molecular profiling may provide prognostic information worthy of validation in larger independent cohorts.

    View details for DOI 10.4132/jptm.2026.07.27

    View details for PubMedID 42723305

  • Comparative Proteomic Analysis of Osteoarthritis and Rheumatoid Arthritis: Identifying Potential Biomarkers JOURNAL OF ORTHOPAEDIC RESEARCH Kaur, B., Rana, D., Konar, M., Sharma, R., Chouhan, D. K., Saini, U., Prakash, M., Arora, A., Dhillon, M. S., Kaur, J., Verma, I., Sharma, S. 2025; 43 (8): 1396-1412

    Abstract

    This study investigates proteomic differences between knee osteoarthritis (OA) and rheumatoid arthritis (RA) to identify protein signatures with potential diagnostic and therapeutic relevance. Using SWATH mass spectrometry, synovial fluid proteome from OA patients across Kellgren-Lawrence OA grades 2, 3, and 4 was analyzed and compared with RA patients. Out of 333 quantified proteins, 45 were differentially expressed, including aggrecan, versican, and inflammation-related proteins (e.g., CRP, APCS, S100A8, and SAA2). ELISA validation confirmed aggrecan, versican, and cartilage oligomeric matrix protein (COMP) as significantly altered proteins in OA compared to RA, along with distinct trends with OA progression and mirrored patterns in paired serum samples. ROC curve analysis highlighted COMP's strong diagnostic potential, with an AUC of 96%, 87.2%, and 85.2% for OA grades 2, 3, and 4 versus RA, respectively. COMP differentiated OA from RA at a synovial fluid concentration of < 3136 ng/mL, AUC of 92.1%, 89% sensitivity, and 82% specificity. Versican also demonstrated diagnostic utility, particularly in later OA stages. Gender-specific analysis revealed no differences for aggrecan and versican, while COMP levels were significantly higher in males. Simultaneously, a lower aggrecan, versican, and COMP levels were observed in OA (females) as compared to RA, potentially linked to estrogen decline with age and cartilage degradation. However, gender variability underscores the need for a larger, sex-balanced cohort study. Future studies could aim to account for validating COMP's diagnostic potential with healthy controls, demonstrating its reliability to characterize different OA grades.

    View details for DOI 10.1002/jor.26092

    View details for Web of Science ID 001497771500001

    View details for PubMedID 40426329

  • Secretome Derived From Mesenchymal Stem Cells Cultured as Monolayer Show Enhanced Bone Regeneration Compared to Secretome From 3D Spheroid - Clues From the Proteome ADVANCED HEALTHCARE MATERIALS Raik, S., Kaur, B., Kumar, S., Rattan, V., Kumar, N., Bhattacharyya, S. 2025; 14 (15): e2500885

    Abstract

    Repair and reconstruction of critical-sized bone defects present a significant challenge due to poor clinical outcomes of conventional bone repair strategies, such as autologous and allogenic bone grafts. The present study underscores the potential of human dental pulp stem cell-derived trophic factors to promote bone repair and regeneration, thus evading the risks associated with cell-based therapy. This study utilizes pre-osteoblast cells to evaluate the osteogenic potential of 2 Dimensional (2D) and 3 Dimensional (3D) secretome from monolayer and spheroid cultures of dental pulp stem cells (DPSCs), respectively. In-vitro results on pre-osteoblast cells (MC3T3-EI) treated with 2D and 3D secretome reveal lower mineralization and mRNA expression of osteogenic specific genes in 3D secretome in comparison to 2D secretome. Furthermore, 2D secretome shows better bone regeneration ability in rat models of calvarial bone defect compared to the 3D secretome. The proteomic profiles of 2D and 3D secretomes are also in concordance with these results and reveal key molecules governing bone regeneration potential. This data highlights the influence of culture conditions on the secretory pattern of mesenchymal stem cells and provides valuable insights for the development of a more effective secretome-based cell-free alternative for novel bone repair and regeneration.

    View details for DOI 10.1002/adhm.202500885

    View details for Web of Science ID 001469361100001

    View details for PubMedID 40249147

  • Synovial fluid glycoproteome profiling in knee osteoarthritis: Molecular insights into type 2 diabetes-associated biomarkers and therapeutic targets BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS Konar, M., Kaur, B., Saini, U., Bhadada, S. K., Sharma, S. 2025; 1873 (4): 141067

    Abstract

    Type 2 diabetes mellitus (T2DM) and Osteoarthritis (OA) share common risk factors like age, obesity and hypertension. Currently, 52 % of diabetic patients suffer from arthritis. Diabetes facilitates OA by altering lipid metabolism, levels of adipokines & cytokines, accumulation of advanced glycation end products, etc., which affects cartilage & bone health. However, the molecular mechanisms of the association of OA with T2DM remain unexplored. Since diabetes greatly affects the glycosylation status of proteins, the present study focused on identifying glycoproteins that could serve as diagnostic and prognostic markers for identifying osteoarthritis in diabetic individuals by LC-MS/MS. Comparative proteomic analysis revealed 20 significantly altered glycoproteins; among them, thyroxine-binding globulin (THBG), alpha-1-antitrypsin (A1AT), fibrinogen gamma chain (FGG) and angiotensinogen (AGT) were further validated. THBG, A1AT and AGT showed promising potential to identify the comorbid condition in serum and synovial fluid, however, ROC analysis identified THBG as the best candidate glycoprotein marker. Upregulation of THBG in OADM disrupts the bone remodeling cycle, degrades insulin, and promotes the expression of GLUT-1 and MMP-9. Overall, THBG could also serve as a therapeutic target for reducing the progression of osteoarthritis and alleviating pain and bone stiffness associated with the disease.

    View details for DOI 10.1016/j.bbapap.2025.141067

    View details for Web of Science ID 001464907500001

    View details for PubMedID 40157439

  • Natural angiotensin II type 1 receptor inhibitors: Virtual screening and<i> in</i><i> vitro</i> evaluation of beta-1,2,3,4,6-penta-O-galloyl-D-glucopyranose, icarrin, and sesamin for osteoarthritis therapy INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Kaur, B., Singh, H., Choudhary, G., Prakash, A., Medhi, B., Chatterjee, D., Saini, U., Kaur, J., Verma, I., Sharma, S. 2025; 309: 142184
  • Proteomic Insights Into Early Detection and Progression of Knee Osteoarthritis: Unveiling Molecular Signatures ARCHIVES OF MEDICAL RESEARCH Kaur, B., Rana, D., Sharma, R., Konar, M., Dhillon, M. S., Chouhan, D. K., Saini, U., Prakash, M., Arora, A., Verma, I., Kaur, J., Sharma, S. 2025; 56 (5): 103206

    Abstract

    Osteoarthritis (OA) is the eleventh most disabling condition, with radiographic classification based on the Kellgren-Lawrence (KL) grading system. Early detection is critical to implement interventions to slow disease progression and improve patient outcomes. Proteomics, as a powerful strategy, could contribute to a better understanding of the disease pathophysiology and its early detection.The study aims to identify and confirm proteins associated with early detection and their role in the progression of knee OA.Synovial fluid (SF) and serum samples from the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, were categorized by KL classification and subjected to SWATHTM analysis in the discovery phase. Seven samples of each OA grade were analyzed. A mass dynamics tool was used for data analysis and visualization. Significant protein expression level was defined as -1≤ log2FC ≥1 with p-value <0.05, and ELISA was used for validation in a greater number of patients.29 significantly modulated proteins were observed in osteoarthritis grade comparisons. Cathepsin G (CTSG) and angiotensinogen (AGT) were upregulated, whereas fumarylacetoacetase (FAH) and neural cell adhesion molecule 1 (NCAM1) were downregulated with radiographic disease progression, as validated by ELISA. CTSG, AGT, and NCAM1 showed good sensitivity and specificity in discriminating between early and late OA grades. Notably, serum and synovial fluid levels of AGT and NCAM1 exhibited significant correlation.This is one of the first studies to comprehensively analyze proteins associated with OA progression. Additionally, the identified protein signatures have great potential for OA progression and differential diagnosis of early and late-stage OA.

    View details for DOI 10.1016/j.arcmed.2025.103206

    View details for Web of Science ID 001462249300001

    View details for PubMedID 40174302

  • Proteomic-based identification of APCS as candidate protein for diagnosis of patients exhibiting anti-tubercular drug induced liver injury SCIENTIFIC REPORTS Kaur, B., Dixit, R., Bakshi, S., Konar, M., Sinha, S. K., Duseja, A., Sharma, S. 2023; 13 (1): 10135

    Abstract

    Traditional markers evaluate anti-tubercular drug-induced liver injury (AT-DILI). However, these markers have certain limitations and studies are in progress to characterize AT-DILI at an early stage. In the present study, 40 patients were categorized and equally distributed into healthy controls, newly diagnosed tuberculosis (TB), TB without hepatotoxicity and TB with hepatotoxicity groups based on their conventional liver function tests. Relative protein quantification was performed on depleted pooled serum samples of each representative group by LC-MS/MS, and validation of shortlisted protein was done by ELISA. Levels of all analysed biochemical parameters showed a statistical increment in the hepatotoxicity group compared to the other three groups, representing AT-DILI. Comparative proteomic analysis between TB with hepatotoxicity versus TB without hepatotoxicity groups highlighted 24 significant differentially expressed proteins, including PROS1, KNG1, CFH, LCAT, APCS and ADIPOQ. Identified proteins were involved in complement activation, triglyceride-rich lipoprotein particle remodelling and pathways comprising complement, coagulation cascades and cholesterol metabolism. Based on functional relevance, the serum amyloid P component (APCS) was shortlisted for validation, and it showed a similar trend as observed in the discovery phase with 100% sensitivity and 87% specificity; however, findings need exploration in larger cohorts.

    View details for DOI 10.1038/s41598-023-35930-x

    View details for Web of Science ID 001018507300043

    View details for PubMedID 37349331

    View details for PubMedCentralID PMC10287637

  • In vitro and in vivo evaluation of dual Clofazimine and Verapamil loaded PLGA nanoparticles INDIAN JOURNAL OF CLINICAL BIOCHEMISTRY Kaur, B., Kaur, M., Ahlawat, P., Sharma, S. 2023; 38 (4): 466-474

    Abstract

    Combination therapy may counter the risk caused by efflux pumps mediated resistance developed by mycobacteria with a concomitant increase of the bactericidal effect of anti-TB drugs. In the present study, combination of two drugs in a nanoformulation was prepared. Clofazimine targets type 2 NADH dehydrogenase of the electron transport chain, and Verapamil inhibits various mycobacterial efflux pumps. The nanotechnology approach was adopted to overcome limitations associated with administration of free form of drugs by using poly (D, L-lactic-co-glycolic acid) as a polymer. Nanoparticles were prepared by oil/water single emulsion solvent evaporation procedure and characterized by various techniques. The results thus highlighted that developed nanoparticles were spherical with nano range size (200-450 nm). Fourier transform infrared spectroscopy revealed successful encapsulation of drugs in developed nanoformulations. Drugs in combination showed higher encapsulation efficiency and percentage drug loading capacity as compared to individual drug nanoformulations. Also, reduced toxicity of nanoformulation was observed in hemolysis assay as compared to free drugs. Ex-vivo analysis demonstrated efficient uptake of rhodamine encapsulated nanoparticles by THP-1 cells, while in-vivo results revealed sustained drug release of nanoformulation as compared to free drugs in combination. Therefore, we were able to achieve development of a single nanoformulation encapsulating Clofazimine and Verapamil in combination. Based on these findings, future studies can be designed to explore the potential of co-encapsulated Clofazimine and Verapamil nanoparticles in management of tuberculosis.The online version contains supplementary material available at 10.1007/s12291-022-01062-8.

    View details for DOI 10.1007/s12291-022-01062-8

    View details for Web of Science ID 000850397300006

    View details for PubMedID 37746540

    View details for PubMedCentralID PMC10516816

  • Noncoding RNAs as novel immunotherapeutic tools against cancer IMMUNOTHERAPEUTICS, VOL. 129 Kaur, M., Kaur, B., Konar, M., Sharma, S. edited by Donev, R. 2022: 135-161

    Abstract

    Immunotherapy is implemented as an important treatment strategy in various malignancies. In cancer, immunotherapy is employed for successful killing of tumor cells with high specificity and greater efficacy, with minimum side effects. Despite various available strategies, cellular immunotherapy including innate (NK cells, macrophages, dendritic cells) and adaptive (B cells and T cells) immune cells plays a critical role in tumor microenvironment. Since past few years, many drugs targeting immune checkpoint proteins including CTLA-4 and PD-1/PD-L1 have been investigated as immunotherapy approach against cancer but complete effectiveness still remains a question, as diverse mechanisms involved in tumorigenesis may result in the development of cancer cell resistance. Number of evidences have highlighted the significant role of non-coding RNAs (ncRNAs) in regulating multiple stages of cancer initiation, progression & immunity. ncRNAs comprises 98% human transcriptome and are basically considered as dark genome. Among ncRNAs, miRNAs and lncRNAs have been extensively studied in regulating diverse processes of cancer tumorigenesis. Upregulation of oncogenic and downregulation of tumor suppressive miRNAs/lncRNAs has been reported to facilitate the cancer progression and invasiveness. This chapter summarizes how an interplay between ncRNAs and immune cells in cancer pathogenesis can be therapeutically targeted to improve current treatment regimen. Strategies should be employed to improve the efficacy and reduce off-target effects of ncRNA based immunotherapy. Henceforth, combination of ncRNAs and available immunotherapy can be argued to enhance the efficacy of existing immunotherapeutic approaches against cancer to improve patient's survival.

    View details for DOI 10.1016/bs.apcsb.2021.11.011

    View details for Web of Science ID 000873715900004

    View details for PubMedID 35305717