Bio


Amruta Bhate is a Postdoctoral Scholar in the Department of Genetics at Stanford University. Amruta holds a PhD in Biochemistry from the University of Illinois, Urbana-Champaign. Her basic research interests include RNA editing, cancer immunology, and autoimmune disease. Her current research focuses on the studying the role of RNA editing in cancer.

Professional Education


  • Doctor of Philosophy, University of Illinois, Urbana-Champaign, Biochemistry (2017)
  • Master of Science, University of Mumbai, India, Biochemistry (2011)
  • Bachelor of Science, University of Mumbai, India, Biochemistry (2009)

Stanford Advisors


  • Jin Li, Postdoctoral Faculty Sponsor

All Publications


  • Zinc Finger RNA-Binding Protein Zn72D Regulates ADAR-Mediated RNA Editing in Neurons. Cell reports Sapiro, A. L., Freund, E. C., Restrepo, L. n., Qiao, H. H., Bhate, A. n., Li, Q. n., Ni, J. Q., Mosca, T. J., Li, J. B. 2020; 31 (7): 107654

    Abstract

    Adenosine-to-inosine RNA editing, catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes, alters RNA sequences from those encoded by DNA. These editing events are dynamically regulated, but few trans regulators of ADARs are known in vivo. Here, we screen RNA-binding proteins for roles in editing regulation with knockdown experiments in the Drosophila brain. We identify zinc-finger protein at 72D (Zn72D) as a regulator of editing levels at a majority of editing sites in the brain. Zn72D both regulates ADAR protein levels and interacts with ADAR in an RNA-dependent fashion, and similar to ADAR, Zn72D is necessary to maintain proper neuromuscular junction architecture and fly mobility. Furthermore, Zn72D's regulatory role in RNA editing is conserved because the mammalian homolog of Zn72D, Zfr, regulates editing in mouse primary neurons. The broad and conserved regulation of ADAR editing by Zn72D in neurons sustains critically important editing events.

    View details for DOI 10.1016/j.celrep.2020.107654

    View details for PubMedID 32433963

  • ADAR1: A New Target for Immuno-oncology Therapy. Molecular cell Bhate, A., Sun, T., Li, J. B. 2019; 73 (5): 866–68

    Abstract

    Three recent studies by Ishizuka etal. (2019), Liu etal. (2019), and Gannon etal. (2018) show that deleting RNA editing enzyme ADAR1 could induce higher cell lethality and render tumor cells more vulnerable to immunotherapy, pinpointing ADAR1 as a new immuno-oncology target.

    View details for PubMedID 30849393

  • Alternative splicing rewires Hippo signaling pathway in hepatocytes to promote liver regeneration. Nature structural & molecular biology Bangru, S., Arif, W., Seimetz, J., Bhate, A., Chen, J., Rashan, E. H., Carstens, R. P., Anakk, S., Kalsotra, A. 2018; 25 (10): 928-939

    Abstract

    During liver regeneration, most new hepatocytes arise via self-duplication; yet, the underlying mechanisms that drive hepatocyte proliferation following injury remain poorly defined. By combining high-resolution transcriptome and polysome profiling of hepatocytes purified from quiescent and toxin-injured mouse livers, we uncover pervasive alterations in messenger RNA translation of metabolic and RNA-processing factors, which modulate the protein levels of a set of splicing regulators. Specifically, downregulation of the splicing regulator ESRP2 activates a neonatal alternative splicing program that rewires the Hippo signaling pathway in regenerating hepatocytes. We show that production of neonatal splice isoforms attenuates Hippo signaling, enables greater transcriptional activation of downstream target genes, and facilitates liver regeneration. We further demonstrate that ESRP2 deletion in mice causes excessive hepatocyte proliferation upon injury, whereas forced expression of ESRP2 inhibits proliferation by suppressing the expression of neonatal Hippo pathway isoforms. Thus, our findings reveal an alternative splicing axis that supports regeneration following chronic liver injury.

    View details for DOI 10.1038/s41594-018-0129-2

    View details for PubMedID 30250226

    View details for PubMedCentralID PMC6173981

  • ESRP2 controls an adult splicing programme in hepatocytes to support postnatal liver maturation. Nature communications Bhate, A., Parker, D. J., Bebee, T. W., Ahn, J., Arif, W., Rashan, E. H., Chorghade, S., Chau, A., Lee, J. H., Anakk, S., Carstens, R. P., Xiao, X., Kalsotra, A. 2015; 6: 8768

    Abstract

    Although major genetic networks controlling early liver specification and morphogenesis are known, the mechanisms responsible for postnatal hepatic maturation are poorly understood. Here we employ global analyses of the mouse liver transcriptome to demonstrate that postnatal remodelling of the liver is accompanied by large-scale transcriptional and post-transcriptional transitions that are cell-type-specific and temporally coordinated. Combining detailed expression analyses with gain- and loss-of-function studies, we identify epithelial splicing regulatory protein 2 (ESRP2) as a conserved regulatory factor that controls the neonatal-to-adult switch of ∼20% of splice isoforms in mouse and human hepatocytes. The normal shift in splicing coincides tightly with dramatic postnatal induction of ESRP2 in hepatocytes. We further demonstrate that forced expression of ESRP2 in immature mouse and human hepatocytes is sufficient to drive a reciprocal shift in splicing and causes various physiological abnormalities. These findings define a direct role for ESRP2 in the generation of conserved repertoires of adult splice isoforms that facilitate terminal differentiation and maturation of hepatocytes.

    View details for DOI 10.1038/ncomms9768

    View details for PubMedID 26531099

    View details for PubMedCentralID PMC4635967

  • Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma. BMC cancer Alam, H., Bhate, A. V., Gangadaran, P., Sawant, S. S., Salot, S., Sehgal, L., Dange, P. P., Chaukar, D. A., D'cruz, A. K., Kannanl, S., Gude, R., Kane, S., Dalal, S. N., Vaidya, M. M. 2012; 12: 32

    Abstract

    Fascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC). Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC.To understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131) using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients.Fascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (P = 0.041), increased lymph node metastasis (P = 0.001), less differentiation (P = 0.005), increased recurrence (P = 0.038) and shorter survival (P = 0.004) of the patients.In conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and treatment of OSCC.

    View details for DOI 10.1186/1471-2407-12-32

    View details for PubMedID 22264292

    View details for PubMedCentralID PMC3329405

  • Loss of keratin 8 phosphorylation leads to increased tumor progression and correlates with clinico-pathological parameters of OSCC patients. PloS one Alam, H., Gangadaran, P., Bhate, A. V., Chaukar, D. A., Sawant, S. S., Tiwari, R., Bobade, J., Kannan, S., D'cruz, A. K., Kane, S., Vaidya, M. M. 2011; 6 (11): e27767

    Abstract

    Keratins are cytoplasmic intermediate filament proteins expressed in tissue specific and differentiation dependent manner. Keratins 8 and 18 (K8 and K18) are predominantly expressed in simple epithelial tissues and perform both mechanical and regulatory functions. Aberrant expression of K8 and K18 is associated with neoplastic progression, invasion and poor prognosis in human oral squamous cell carcinomas (OSCCs). K8 and K18 undergo several post-translational modifications including phosphorylation, which are known to regulate their functions in various cellular processes. Although, K8 and K18 phosphorylation is known to regulate cell cycle, cell growth and apoptosis, its significance in cell migration and/or neoplastic progression is largely unknown. In the present study we have investigated the role of K8 phosphorylation in cell migration and/or neoplastic progression in OSCC.To understand the role of K8 phosphorylation in neoplastic progression of OSCC, shRNA-resistant K8 phospho-mutants of Ser73 and Ser431 were overexpressed in K8-knockdown human AW13516 cells (derived from SCC of tongue; generated previously). Wound healing assays and tumor growth in NOD-SCID mice were performed to analyze the cell motility and tumorigenicity respectively in overexpressed clones. The overexpressed K8 phospho-mutants clones showed significant increase in cell migration and tumorigenicity as compared with K8 wild type clones. Furthermore, loss of K8 Ser73 and Ser431 phosphorylation was also observed in human OSCC tissues analyzed by immunohistochemistry, where their dephosphorylation significantly correlated with size, lymph node metastasis and stage of the tumor.Our results provide first evidence of a potential role of K8 phosphorylation in cell migration and/or tumorigenicity in OSCC. Moreover, correlation studies of K8 dephosphorylation with clinico-pathological parameters of OSCC patients also suggest its possible use in prognostication of human OSCC.

    View details for DOI 10.1371/journal.pone.0027767

    View details for PubMedID 22114688

    View details for PubMedCentralID PMC3219681