Abantika Ganguly
Basic Life Research Scientist, Rad/Pediatric Radiology
Bio
Dr.Abantika Ganguly is a researcher specializing in molecular biology and bioinformatics. She holds a Bachelors and Masters in Chemistry and earned her PhD in Molecular Biophysics from Indian Institute of Science, India where she explored the global transcriptional regulation governing switch ON/OFF of genes under various stress stimuli. Dr Ganguly went onto do her postdoctoral studies at The Scripps Research Institute, where she was further involved in using NGS based analysis to understand the role of different genes in conferring resistance/susceptibility against common oncogenic drugs. She has worked as scientific advisor to a genomic start-up in developing custom NGS pipelines based on client needs. She has also Currently she works with Avnesh Thakor to develop stem cell based cell therapies based on disease-etiology related to Inflammatory Diseases with no approved FDA biologics using multi-omics and translational approaches.
Current Role at Stanford
Research Scientist
Honors & Awards
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Outstanding Thesis Award (Asia)- Second Prize, Eli Lilly (2012)
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Review Editor, Frontiers in Immunology (2024-present)
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Reviewer, BBA-Molecular Basis of Diseases (2023-present)
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Reviewer, Langmuir (2016)
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Reviewer, BMC Genomics (2016-present)
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Reviewer, BMC Genetics (2017-present)
Education & Certifications
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BSc, Presidency College, Chemistry (2004)
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MSc, IIT, Kanpur, Chemistry (2006)
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PhD, Indian Institute of Science, Molecular Biophysics (2012)
Patents
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THAKOR. Avnesh S, GANGULY. Abantika, CHETTY. Shashank, REGMI. Shobha. "United States Patent WO2023077160 METHODS OF TREATING DISEASES ASSOCIATED WITH CELLULAR-ENERGY DEFICIENCY OR MITOCHONDRIAL DYSFUNCTION BY LOCOREGIONAL DELIVERY OF EXTRACELLULAR VESICLES THAT HAVE A CARGO WITH AN ENHANCED BIOENERGETIC PROFILE", THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY, Apr 5, 2023
Skills and Expertise
All Publications
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Evaluating the therapeutic potential of different sources of mesenchymal stem cells in acute respiratory distress syndrome.
Stem cell research & therapy
2024; 15 (1): 385
Abstract
Mesenchymal stem/stromal cells (MSCs) have attracted interest as a potential therapy given their anti-inflammatory and immunomodulatory properties. However, clinical trials using MSCs for acute respiratory distress syndrome (ARDS) have produced mixed and inconclusive data. In previous work, we performed a "head-to-head" comparison between different sources of MSCs and showed that each source had a unique genomic and proteomic "signature".This study investigated which sources of MSC: bone marrow derived-MSCs (BM-MSCs), adipose tissue derived-MSCs (AD-MSCs) and umbilical cord derived-MSCs (UC-MSCs) would be the optimal candidate to be used as a therapy in an LPS-induced mouse model of ARDS. Immune cells assessment, tissue transcriptomics, animal survival, and endothelial-epithelial barrier assessment were used to evaluate their effects.When comparing the three most commonly used MSC sources, we found that UC-MSCs exhibited greater efficacy compared to other MSCs in improving animal survival, mitigating epithelial/endothelial damage, decreasing lung inflammation via reducing neutrophil infiltration, T cell proliferation, and M1 polarization. Bulk RNA sequencing of lung tissue also showed that UC-MSCs have the capability to downregulate extracellular trap formation, by the downregulation of key genes like Elane and Padi4. Notably, treatment with UC-MSCs demonstrated a significant reduction in Fc-γ R mediated phagocytosis, which has been associated with monocyte pyroptosis and intense inflammation in the context of COVID-19.Our findings suggest that UC-MSCs are an optimal source of MSC to treat acute inflammatory conditions in the lungs, such as ARDS.
View details for DOI 10.1186/s13287-024-03977-w
View details for PubMedID 39468662
View details for PubMedCentralID PMC11520775
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Time-course analysis of cisplatin induced AKI in preclinical models: implications for testing different sources of MSCs.
Journal of translational medicine
2024; 22 (1): 789
Abstract
Kidneys are at risk from drug-induced toxicity, with a significant proportion of acute kidney injury (AKI) linked to medications, particularly cisplatin. Existing cytoprotective drugs for cisplatin-AKI carry side effects, prompting a search for better biological therapies. Mesenchymal Stem Cells (MSCs) are under consideration given their regenerative properties, yet their clinical application has not achieved their full potential, mainly due to variability in the source of MSC tested. In addition, translating treatments from rodent models to humans remains challenging due to a lack of standardized dosing and understanding potential differential responses to cisplatin between animal strains.In the current study, we performed a time-course analysis of the effect of cisplatin across different mouse strains and evaluated gender related differences to create a robust preclinical model that could then be used to explore the therapeutic efficacy of different sources of MSCs for their ability to reverse AKI.Our data indicated that different mouse strains produce differential responses to the same cisplatin dosing regimen. Despite this, we did not observe any gender-related bias towards cisplatin nephrotoxicity. Furthermore, our time-course analysis identified that cisplatin-induced inflammation was driven by a strong CXCL1 response, which was used as a putative biomarker to evaluate the comparative therapeutic efficacy of different MSC sources in reversing AKI. Our data indicates that UC-MSCs have a stronger anti-inflammatory effect compared to BM-MSCs and AD-MSCs, which helped to ameliorate cisplatin-AKI.Overall, our data underscores the importance of using an optimized preclinical model of cisplatin-AKI to test different therapies. We identified CXCL1 as a potential biomarker of cisplatin-AKI and identified the superior efficacy of UC-MSCs in mitigating cisplatin-AKI.
View details for DOI 10.1186/s12967-024-05439-6
View details for PubMedID 39192240
View details for PubMedCentralID 4146684
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Integrated transcriptome-proteome analyses of human stem cells reveal source-dependent differences in their regenerative signature.
Stem cell reports
2022
Abstract
Mesenchymal stem cells (MSCs) are gaining increasing prominence as an effective regenerative cellular therapy. However, ensuring consistent and reliable effects across clinical populations has proved to be challenging. In part, this can be attributed to heterogeneity in the intrinsic molecular and regenerative signature of MSCs, which is dependent on their source of origin. The present work uses integrated omics-based profiling, at different functional levels, to compare the anti-inflammatory, immunomodulatory, and angiogenic properties between MSCs from neonatal (umbilical cord MSC [UC-MSC]) and adult (adipose tissue MSC [AD-MSC], and bone marrow MSC [BM-MSC]) sources. Using multi-parametric analyses, we identified that UC-MSCs promote a more robust host innate immune response; in contrast, adult-MSCs appear to facilitate remodeling of the extracellular matrix (ECM) with stronger activation of angiogenic cascades. These data should help facilitate the standardization of source-specific MSCs, such that their regenerative signatures can be confidently used to target specific disease processes.
View details for DOI 10.1016/j.stemcr.2022.11.006
View details for PubMedID 36493779
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Global Fitness Profiling Identifies Arsenic and Cadmium Tolerance Mechanisms in Fission Yeast.
G3 (Bethesda, Md.)
2016; 6 (10): 3317-3333
Abstract
Heavy metals and metalloids such as cadmium [Cd(II)] and arsenic [As(III)] are widespread environmental toxicants responsible for multiple adverse health effects in humans. However, the molecular mechanisms underlying metal-induced cytotoxicity and carcinogenesis, as well as the detoxification and tolerance pathways, are incompletely understood. Here, we use global fitness profiling by barcode sequencing to quantitatively survey the Schizosaccharomyces pombe haploid deletome for genes that confer tolerance of cadmium or arsenic. We identified 106 genes required for cadmium resistance and 110 genes required for arsenic resistance, with a highly significant overlap of 36 genes. A subset of these 36 genes account for almost all proteins required for incorporating sulfur into the cysteine-rich glutathione and phytochelatin peptides that chelate cadmium and arsenic. A requirement for Mms19 is explained by its role in directing iron-sulfur cluster assembly into sulfite reductase as opposed to promoting DNA repair, as DNA damage response genes were not enriched among those required for cadmium or arsenic tolerance. Ubiquinone, siroheme, and pyridoxal 5'-phosphate biosynthesis were also identified as critical for Cd/As tolerance. Arsenic-specific pathways included prefoldin-mediated assembly of unfolded proteins and protein targeting to the peroxisome, whereas cadmium-specific pathways included plasma membrane and vacuolar transporters, as well as Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional coactivator that controls expression of key genes required for cadmium tolerance. Notable differences are apparent with corresponding screens in the budding yeast Saccharomyces cerevisiae, underscoring the utility of analyzing toxic metal defense mechanisms in both organisms.
View details for DOI 10.1534/g3.116.033829
View details for PubMedID 27558664
View details for PubMedCentralID PMC5068951
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A comparative kinetic and thermodynamic perspective of the σ-competition model in Escherichia coli.
Biophysical journal
2012; 103 (6): 1325-33
Abstract
Transcription is the most fundamental step in gene expression in any living organism. Various environmental cues help in the maturation of core RNA polymerase (RNAP; α(2)ββ'ω) with different σ-factors, leading to the directed recruitment of RNAP to different promoter DNA sequences. Thus it is essential to determine the σ-factors that affect the preferential partitioning of core RNAP among various σ-actors, and the role of σ-switching in transcriptional gene regulation. Further, the macromolecular assembly of holo RNAP takes place in an extremely crowded environment within a cell, and thus far the kinetics and thermodynamics of this molecular recognition process have not been well addressed. In this study we used a site-directed bioaffinity immobilization method to evaluate the relative binding affinities of three different Escherichia coli σ-factors to the same core RNAP with variations in temperature and ionic strength while emulating the crowded cellular milieu. Our data indicate that the interaction of core RNAP-σ is susceptible to changes in external stimuli such as osmolytic and thermal stress, and the degree of susceptibility varies among different σ-factors. This allows for a reversible σ-switching from housekeeping factors to alternate σ-factors when the organism senses a change in its physiological conditions.
View details for DOI 10.1016/j.bpj.2012.08.013
View details for PubMedID 22995505
View details for PubMedCentralID PMC3446719
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Precision Delivery of Therapeutics to the Intestine: A Case Series of Superselective Steroid Administration in Pediatric Intestinal Transplant Recipients.
Transplantation
2024; 108 (8): e202-e203
View details for DOI 10.1097/TP.0000000000005053
View details for PubMedID 39042371
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Mesenchymal stem cell-derived extracellular vesicles for the treatment of acute rejection in pediatric and adult bowel transplant
AMERICAN JOURNAL OF TRANSPLANTATION
2024; 24 (4): 693-696
View details for DOI 10.1016/j.ajt.2023.10.019
View details for Web of Science ID 001217324600001
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Precision Delivery of Human Bone Marrow-Derived Mesenchymal Stem Cells Into the Pancreas Via Intra-arterial Injection Prevents the Onset of Diabetes.
Stem cells translational medicine
2024
Abstract
Mesenchymal stem cells (MSCs) are a promising therapy to potentially treat diabetes given their potent anti-inflammatory and immune-modulatory properties. While these regenerative cells have shown considerable promise in cell culture, their clinical translation has been challenging. In part, this can be attributed to these cells not reaching the pancreas to exert their regenerative effects following conventional intravenous (IV) injection, with the majority of cells being trapped in the lungs in the pulmonary first-pass effect. In the present study, we will therefore examine whether direct delivery of MSCs to the pancreas via an intra-arterial (IA) injection can improve their therapeutic efficacy. Using a mouse model, in which repetitive low doses of STZ induced a gentle, but progressive, hyperglycemia, we tested bone marrow-derived MSCs (BM-MSCs) which we have shown are enriched with pro-angiogenic and immunomodulatory factors. In cell culture studies, BM-MSCs were shown to preserve islet viability and function following exposure to proinflammatory cytokines (IFN-gamma, IL-1beta, and TNF-alpha) through an increase in pAkt. When tested in our animal model, mice receiving IV BM-MSCs were not able to mitigate the effects of STZ, however those which received the same dose and batch of cells via IA injection were able to maintain basal and dynamic glycemic control, to similar levels as seen in healthy control animals, over 10 days. This study shows the importance of considering precision delivery approaches to ensure cell-based therapies reach their intended targets to enable them to exert their therapeutic effects.
View details for DOI 10.1093/stcltm/szae020
View details for PubMedID 38530131
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Mesenchymal stem cell-derived extracellular vesicles for the treatment of acute rejection in pediatric and adult bowel transplant.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
2023
Abstract
Mesenchymal stem cells are under investigation as a novel therapy to treat solid organ transplant rejection. However, significant hurdles have limited their use in humans. Mesenchymal stem cell-derived extracellular vesicles address many of these shortcomings but have not been investigated clinically. Here we report our experience treating two patients with graft rejection and inflammation following bowel transplant using mesenchymal stem cell-derived extracellular vesicles.
View details for DOI 10.1016/j.ajt.2023.10.019
View details for PubMedID 39491097
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β Cell and Autophagy: What Do We Know?
Biomolecules
2023; 13 (4)
Abstract
Pancreatic β cells are central to glycemic regulation through insulin production. Studies show autophagy as an essential process in β cell function and fate. Autophagy is a catabolic cellular process that regulates cell homeostasis by recycling surplus or damaged cell components. Impaired autophagy results in β cell loss of function and apoptosis and, as a result, diabetes initiation and progress. It has been shown that in response to endoplasmic reticulum stress, inflammation, and high metabolic demands, autophagy affects β cell function, insulin synthesis, and secretion. This review highlights recent evidence regarding how autophagy can affect β cells' fate in the pathogenesis of diabetes. Furthermore, we discuss the role of important intrinsic and extrinsic autophagy modulators, which can lead to β cell failure.
View details for DOI 10.3390/biom13040649
View details for PubMedID 37189396
View details for PubMedCentralID PMC10136307
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Case Series of Precision Delivery of Methylprednisolone in Pediatric Inflammatory Bowel Disease: Feasibility, Clinical Outcomes, and Identification of a Vasculitic Transcriptional Program.
Journal of clinical medicine
2023; 12 (6)
Abstract
Systemic steroid exposure, while useful for the treatment of acute flares in inflammatory bowel disease (IBD), is associated with an array of side effects that are particularly significant in children. Technical advancements have enabled locoregional intraarterial steroid delivery directly into specific segments of the gastrointestinal tract, thereby maximizing tissue concentration while limiting systemic exposure. We investigated the feasibility of intraarterial steroid administration into the bowel in a cohort of nine pediatric patients who had IBD. This treatment approach provided symptom relief in all patients, with sustained relief (>2 weeks) in seven out of nine; no serious adverse effects occurred in any patient. In addition, we identified patterns of vascular morphologic changes indicative of a vasculopathy within the mesenteric circulation of inflamed segments of the bowel in pediatric patients with Crohn's disease, which correlated with disease activity. An analysis of publicly available transcriptomic studies identified vasculitis-associated molecular pathways activated in the endothelial cells of patients with active Crohn's disease, suggesting a possible shared transcriptional program between vasculitis and IBD. Intraarterial corticosteroid treatment is safe and has the potential to be widely accepted as a locoregional approach for therapy delivery directly into the bowel; however, this approach still warrants further consideration as a short-term "bridge" between therapy transitions for symptomatic IBD patients with refractory disease, as part of a broader steroid-minimizing treatment strategy.
View details for DOI 10.3390/jcm12062386
View details for PubMedID 36983386
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Precision Delivery of Steroids as a Rescue Therapy for Gastrointestinal Graft-versus-Host Disease in Pediatric Stem Cell Transplant Recipients
Journal of Clinical Medicine
2023; 12 (4229)
View details for DOI 10.3390/jcm12134229
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Umbilical cord mesenchymal stromal cells-from bench to bedside.
Frontiers in cell and developmental biology
2022; 10: 1006295
Abstract
In recent years, mesenchymal stromal cells (MSCs) have generated a lot of attention due to their paracrine and immuno-modulatory properties. mesenchymal stromal cells derived from the umbilical cord (UC) are becoming increasingly recognized as having increased therapeutic potential when compared to mesenchymal stromal cells from other sources. The purpose of this review is to provide an overview of the various compartments of umbilical cord tissue from which mesenchymal stromal cells can be isolated, the differences and similarities with respect to their regenerative and immuno-modulatory properties, as well as the single cell transcriptomic profiles of in vitro expanded and freshly isolated umbilical cord-mesenchymal stromal cells. In addition, we discuss the therapeutic potential and biodistribution of umbilical cord-mesenchymal stromal cells following systemic administration while providing an overview of pre-clinical and clinical trials involving umbilical cord-mesenchymal stromal cells and their associated secretome and extracellular vesicles (EVs). The clinical applications of umbilical cord-mesenchymal stromal cells are also discussed, especially in relation to obstacles and potential solutions for their effective translation from bench to bedside.
View details for DOI 10.3389/fcell.2022.1006295
View details for PubMedID 36313578
View details for PubMedCentralID PMC9597686
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Mesenchymal stromal cells for the treatment of Alzheimer's disease: Strategies and limitations.
Frontiers in molecular neuroscience
2022; 15: 1011225
Abstract
Alzheimer's disease (AD) is a major cause of age-related dementia and is characterized by progressive brain damage that gradually destroys memory and the ability to learn, which ultimately leads to the decline of a patient's ability to perform daily activities. Although some of the pharmacological treatments of AD are available for symptomatic relief, they are not able to limit the progression of AD and have several side effects. Mesenchymal stem/stromal cells (MSCs) could be a potential therapeutic option for treating AD due to their immunomodulatory, anti-inflammatory, regenerative, antioxidant, anti-apoptotic, and neuroprotective effects. MSCs not only secret neuroprotective and anti-inflammatory factors to promote the survival of neurons, but they also transfer functional mitochondria and miRNAs to boost their bioenergetic profile as well as improve microglial clearance of accumulated protein aggregates. This review focuses on different clinical and preclinical studies using MSC as a therapy for treating AD, their outcomes, limitations and the strategies to potentiate their clinical translation.
View details for DOI 10.3389/fnmol.2022.1011225
View details for PubMedID 36277497
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Tdp1 processes chromate-induced single-strand DNA breaks that collapse replication forks.
PLoS genetics
2018; 14 (8): e1007595
Abstract
Hexavalent chromium [Cr(VI)] damages DNA and causes cancer, but it is unclear which DNA damage responses (DDRs) most critically protect cells from chromate toxicity. Here, genome-wide quantitative functional profiling, DDR measurements and genetic interaction assays in Schizosaccharomyces pombe reveal a chromate toxicogenomic profile that closely resembles the cancer chemotherapeutic drug camptothecin (CPT), which traps Topoisomerase 1 (Top1)-DNA covalent complex (Top1cc) at the 3' end of single-stand breaks (SSBs), resulting in replication fork collapse. ATR/Rad3-dependent checkpoints that detect stalled and collapsed replication forks are crucial in Cr(VI)-treated cells, as is Mus81-dependent sister chromatid recombination (SCR) that repairs single-ended double-strand breaks (seDSBs) at broken replication forks. Surprisingly, chromate resistance does not require base excision repair (BER) or interstrand crosslink (ICL) repair, nor does co-elimination of XPA-dependent nucleotide excision repair (NER) and Rad18-mediated post-replication repair (PRR) confer chromate sensitivity in fission yeast. However, co-elimination of Tdp1 tyrosyl-DNA phosphodiesterase and Rad16-Swi10 (XPF-ERCC1) NER endonuclease synergistically enhances chromate toxicity in top1Δ cells. Pnk1 polynucleotide kinase phosphatase (PNKP), which restores 3'-hydroxyl ends to SSBs processed by Tdp1, is also critical for chromate resistance. Loss of Tdp1 ameliorates pnk1Δ chromate sensitivity while enhancing the requirement for Mus81. Thus, Tdp1 and PNKP, which prevent neurodegeneration in humans, repair an important class of Cr-induced SSBs that collapse replication forks.
View details for DOI 10.1371/journal.pgen.1007595
View details for PubMedID 30148840
View details for PubMedCentralID PMC6128646
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Nonspecific interaction between DNA and protein allows for cooperativity: a case study with mycobacterium DNA binding protein.
The journal of physical chemistry. B
2012; 116 (1): 621-32
Abstract
Different DNA-binding proteins have different interaction modes with DNA. Sequence-specific DNA-protein interaction has been mostly associated with regulatory processes inside a cell, and as such extensive studies have been made. Adequate data is also available on nonspecific DNA-protein interaction, as an intermediate to protein's search for its cognate partner. Multidomain nonspecific DNA-protein interaction involving physical sequestering of DNA has often been implicated to regulate gene expression indirectly. However, data available on this type of interaction is limited. One such interaction is the binding of DNA with mycobacterium DNA binding proteins. We have used the Langmuir-Blodgett technique to evaluate for the first time the kinetics and thermodynamics of Mycobacterium smegmatis Dps1 binding to DNA. By immobilizing one of the interacting partners, we have shown that, when a kinetic bottleneck is applied, the binding mechanism showed cooperative binding (n = 2.72) at lower temperatures, but the degree of cooperativity gradually reduces (n = 1.38) as the temperature was increased. We have also compared the kinetics and thermodynamics of sequence-specific and nonspecific DNA-protein interactions under the same set of conditions.
View details for DOI 10.1021/jp209423n
View details for PubMedID 22091866
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Sequential assembly of an active RNA polymerase molecule at the air-water interface.
Langmuir : the ACS journal of surfaces and colloids
2011; 27 (7): 3808-14
Abstract
At the heart of understanding cellular processes lies our ability to explore the specific nature of communication between sequential information carrying biopolymers. However, the data extracted from conventional solution phase studies may not reflect the dynamics of communication between recognized partners as they occur in the crowded cellular milieu. We use the principle of immobilization of histidine-tagged biopolymers at a Ni(II)-encoded Langmuir monolayer to study sequence-specific protein-protein interactions in an artificially crowded environment. The advantage of this technique lies in increasing the surface density of one of the interacting partners that allows us to study macromolecular interactions in a controlled crowded environment, but without compromising the speed of the reactions. We have taken advantage of this technique to follow the sequential assembly process of the multiprotein complex Escherichia coli RNA polymerase at the interface and also deciphered the role of one of the proteins, omega (ω), in the assembly pathway. Our reconstitution studies indicate that in the absence of molecular chaperones or other cofactors, omega (ω) plays a decisive role in refolding the largest protein beta prime (β') and its recruitment into the multimeric assembly to reconstitute an active RNA polymerase. It was also observed that the monolayer had the ability to distinguish between sequence-specific and -nonspecific interactions despite the immobilization of one of the biomacromolecules. The technique provides a universal two-dimensional template for studying protein-ligand interactions while mimicking molecular crowding.
View details for DOI 10.1021/la200225t
View details for PubMedID 21395266
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Sequence specific interaction between promoter DNA and Escherichia coli RNA polymerase: comparative thermodynamic analysis with one immobilized partner.
The journal of physical chemistry. B
2009; 113 (46): 15399-408
Abstract
Sequence specific interaction between DNA and protein molecules has been a subject of active investigation for decades now. Here, we have chosen single promoter containing bacteriophage DeltaD(III) T7 DNA and Escherichia coli RNA polymerase and followed their recognition at the air-water interface by using the surface plasmon resonance (SPR) technique, where the movement of one of the reacting species is restricted by way of arraying them on an immobilized support. For the Langmuir monolayer studies, we used a RNA polymerase with a histidine tag attached to one of its subunits, thus making it an excellent substrate for Ni(II) ions, while the SPR studies were done using biotin-labeled DNA immobilized on a streptavidin-coated chip. Detailed analysis of the thermodynamic parameters as a function of concentration and temperature revealed that the interaction of RNA polymerase with T7 DNA is largely entropy driven (83 (+/-12) kcal mol(-1)) with a positive enthalpy of 13.6 (+/-3.6) kcal mol(-1). The free energy of reaction determined by SPR and Langmuir-Blodgett technique was -11 (+/-2) and -15.6 kcal mol(-1), respectively. The ability of these methods to retain the specificity of the recognition process was also established.
View details for DOI 10.1021/jp9071197
View details for PubMedID 19839610