Ankita Srivastava Research

Mechanisms of impaired liver regeneration in alcohol-associated liver disease

We investigated molecular, cellular, and physiological mechanisms underlying impaired liver regeneration in alcohol-associated liver disease, utilizing rat models and partial hepatectomy. We identified miR-21-driven regulatory networks in hepatic stellate cells and ethanol-mediated disruption of hepatocyte regenerative states. Longitudinal imaging and computational modeling revealed sex-dependent suppression of regeneration. Recently, we developed an AI-based histopathology pipeline to predict physiological hepatic venous pressure gradient from alcoholic hepatitis biopsies.

Parrish A#, Srivastava A#, Juskeviciute E, Hoek JB, Vadigepalli R. Dysregulation of miR-21-associated miRNA regulatory networks by chronic ethanol consumption impairs liver regeneration. Physiol Genomics. 2021 Dec 1;53(12):546-555. doi: 10.1152/physiolgenomics.00113.2021. Epub 2021 Nov 19. PubMed PMID: 34796728; PubMed Central PMCID: PMC8820682. (#joint first authors)

Achanta S, Verma A, Srivastava A, Nilakantan H, Hoek JB, Vadigepalli R. Single-Cell Gene Expression Analysis Identifies Chronic Alcohol-Mediated Shift in Hepatocyte Molecular States After Partial Hepatectomy. Gene Expr. 2019 Apr 18;19(2):97-119. doi: 10.3727/105221618X15361728786767. Epub 2018 Sep 6. PubMed PMID: 30189915; PubMed Central PMCID: PMC6466177.

Barnhart BK, Kan T, Srivastava A, Wessner CE, Waters J, Ambelil M, Eisenbrey JR, Hoek JB, Vadigepalli R. Longitudinal ultrasound imaging and network modeling in rats reveal sex-dependent suppression of liver regeneration after resection in alcoholic liver disease. Front Physiol. 2023;14:1102393. doi: 10.3389/fphys.2023.1102393. eCollection 2023. PubMed PMID: 36969577; PubMed Central PMCID: PMC10033530.

Integrated transcriptomics and histopathology AI for enhancing liver transplantation

Many donated livers are deemed unsuitable for transplantation, even as there is a large unmet demand for liver transplants. We developed an integrated transcriptomics and histopathology AI approach to characterize the donor liver biopsies at the time of organ recovery. We identified a molecular signature distinguishing a subset of rejected livers potentially suitable for transplantation, demonstrating the potential to expand the pool of transplantable livers.

Srivastava A, Manchel A, Waters J, Ambelil M, Barnhart BK, Hoek JB, Shah AP, Vadigepalli R. Integrated transcriptomics and histopathology approach identifies a subset of rejected donor livers with potential suitability for transplantation. BMC Genomics. 2024 May 2;25(1):437. doi: 10.1186/s12864-024-10362-7. PubMed PMID: 38698335; PubMed Central PMCID: PMC11067109.

MicroRNA and gene regulatory networks in autonomic brainstem neural circuits

We generated unique time series transcriptomic datasets from brainstem autonomic circuits during hypertension development in female spontaneously hypertensive rats. We identified extensive transcriptomic changes over time in multiple brainstem regions during the development of hypertension. These findings highlight critical windows of neurogenic dysregulation driving high blood pressure. Towards neuromodulation, we defined the molecular phenotypes of cardiac-projecting neurons in the dorsal motor nucleus of the vagus and identified neuromodulators underlying cardioprotection.

Moss A, Kuttippurathu L, Srivastava A, Schwaber JS, Vadigepalli R. Dynamic dysregulation of transcriptomic networks in brainstem autonomic nuclei during hypertension development in the female spontaneously hypertensive rat. Physiol Genomics. 2024 Mar 1;56(3):283-300. doi: 10.1152/physiolgenomics.00073.2023. PMID: 38145287. Editor's Pick as APSselect March 2024 as the best paper in physiological research.

Moss A, Srivastava A, Kuttippurathu L, Schwaber JS, Vadigepalli R. Dynamic rewiring of microRNA networks in the brainstem autonomic control circuits during hypertension development in the female spontaneously hypertensive rat. Physiol Genomics. 2025 Jul 18. doi: 10.1152/physiolgenomics.00136.2024. PMID: 40679600.

Hornung E, Robbins S, Srivastava A, Achanta S, Chen J, Cheng ZJ, Schwaber J, Vadigepalli R. Neuromodulatory co-expression in cardiac vagal motor neurons of the dorsal motor nucleus of the vagus. iScience. 2024 Aug 16;27(8):110549. doi: 10.1016/j.isci.2024.110549. eCollection 2024 Aug 16. PubMed PMID: 39171288; PubMed Central PMCID: PMC11338141.

Single-cell transcriptomics to study neuroinflammation and gut dysbiosis in opioid withdrawal

Drug-seeking in opioid dependence is due in part to the severe negative emotion associated with the withdrawal syndrome. We developed a single-cell systems biology approach to study opioid withdrawal and demonstrated astrocyte-driven neuroinflammation in the amygdala. We also identified a correlated gut dysbiosis suggesting a possible link between neuroinflammation and gut dysbiosis.

O'Sullivan SJ, Malahias E, Park J, Srivastava A, Reyes BAS, Gorky J, Vadigepalli R, Van Bockstaele EJ, Schwaber JS. Single-Cell Glia and Neuron Gene Expression in the Central Amygdala in Opioid Withdrawal Suggests Inflammation With Correlated Gut Dysbiosis. Front Neurosci. 2019;13:665. doi: 10.3389/fnins.2019.00665. eCollection 2019. PubMed PMID: 31333398; PubMed Central PMCID: PMC6619439.

O'Sullivan SJ#, Srivastava A#, Vadigepalli R, Schwaber JS. Investigating Drivers of Antireward in Addiction Behavior with Anatomically Specific Single-Cell Gene Expression Methods. J Vis Exp. 2022 Aug 4;(186). doi: 10.3791/64014. PubMed PMID: 35993753. (#joint first authors)