Bio

Honors & Awards


  • DAAD Travel fellowship, Cyceron, University of Caen, Caen, France (2013)
  • Travel Award - ISTH 2013, University of Giessen (2013)
  • DAAD Travel fellowship, Theodor Kocher Institute, Bern, Switzerland (2013)
  • DAAD STIBET teaching assistantship, Courses in Bioinformatics - Univesity of Giessen (2010-2013)

Professional Education


  • Doctor of Philosophy, Justus-Liebig-Universität Gießen, Biochemistry, Neuroscience (2014)
  • Master of Science, University of Abertay Dundee, Biotechnology (2006)
  • Bachelor of Science, University of Pune, Microbiology, Chemistry, Zoology (2005)

Stanford Advisors


Publications

All Publications


  • GAPDH (glyceraldehyde-3-phosphate dehydrogenase) Protein-Protein Interaction Inhibitor Reveals a Non-Catalytic Role for GAPDH Oligomerization in Cell Death. The Journal of biological chemistry Qvit, N., Joshi, A. U., Cunningham, A. D., Ferreira, J. C., Mochly-Rosen, D. 2016

    Abstract

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an important glycolytic enzyme, has a non-catalytic (thus a non-canonical) role in inducing mitochondrial elimination under oxidative stress. We recently demonstrated that phosphorylation of GAPDH by delta protein kinase C (PKC) inhibits this GAPDH-dependent mitochondrial elimination. deltaPKC phosphorylation of GAPDH correlates with increased cell injury following oxidative stress, suggesting that inhibiting GAPDH phosphorylation should decrease cell injury. Using rational design, we identified pseudoGAPDH peptide, an inhibitor of deltaPKC-mediated GAPDH phosphorylation that does not inhibit the phosphorylation of other deltaPKC substrates. Unexpectedly, pseudoGAPDH decreased mitochondrial elimination and increased cardiac damage in an animal model of heart attack. Either treatment with pseudoGAPDH or direct phosphorylation of GAPDH by deltaPKC decreased GAPDH tetramerization, which corresponded to reduced GAPDH glycolytic activity in vitro and ex vivo. Taken together, our study identified the potential mechanism by which oxidative stress inhibits the protective GAPDH-mediated elimination of damaged mitochondria. Our study also identified a pharmacological tool, pseudoGAPDH peptide, with interesting properties. pseudoGAPDH peptide is an inhibitor of the interaction between deltaPKC and GAPDH, and of the resulting phosphorylation of GAPDH by deltaPKC. pseudoGAPDH peptide is also an inhibitor of GAPDH oligomerization and thus an inhibitor of GAPDH glycolytic activity. Finally, we found that pseudoGAPDH peptide is an inhibitor of the elimination of damaged mitochondria. We discuss how this unique property of increasing cell damage following oxidative stress suggests a potential use for pseudoGAPDH peptide-based therapy.

    View details for DOI 10.1074/jbc.M115.711630

    View details for PubMedID 27129213

  • VCP recruitment to mitochondria causes mitophagy impairment and neurodegeneration in models of Huntington's disease. Nature communications Guo, X., Sun, X., Hu, D., Wang, Y. J., Fujioka, H., Vyas, R., Chakrapani, S., Joshi, A. U., Luo, Y., Mochly-Rosen, D., Qi, X. 2016; 7: 12646

    Abstract

    Mutant Huntingtin (mtHtt) causes neurodegeneration in Huntington's disease (HD) by evoking defects in the mitochondria, but the underlying mechanisms remains elusive. Our proteomic analysis identifies valosin-containing protein (VCP) as an mtHtt-binding protein on the mitochondria. Here we show that VCP is selectively translocated to the mitochondria, where it is bound to mtHtt in various HD models. Mitochondria-accumulated VCP elicits excessive mitophagy, causing neuronal cell death. Blocking mtHtt/VCP mitochondrial interaction with a peptide, HV-3, abolishes VCP translocation to the mitochondria, corrects excessive mitophagy and reduces cell death in HD mouse- and patient-derived cells and HD transgenic mouse brains. Treatment with HV-3 reduces behavioural and neuropathological phenotypes of HD in both fragment- and full-length mtHtt transgenic mice. Our findings demonstrate a causal role of mtHtt-induced VCP mitochondrial accumulation in HD pathogenesis and suggest that the peptide HV-3 might be a useful tool for developing new therapeutics to treat HD.

    View details for DOI 10.1038/ncomms12646

    View details for PubMedID 27561680

  • The Entangled ER-Mitochondrial axis as a potential therapeutic strategy in Neurodegeneration: A Tangled Duo Unchained Cell Calcium Joshi, A. U., Kornfeld, O. S., Mochly-Rosen, D. 2016
  • Deficiency of Factor VII activating protease alters the outcome of ischemic stroke in mice EUROPEAN JOURNAL OF NEUROSCIENCE Joshi, A. U., Orset, C., Engelhardt, B., Baumgart-Vogt, E., Gerriets, T., Vivien, D., Kanse, S. M. 2015; 41 (7): 963-973

    View details for DOI 10.1111/ejn.12830

    View details for Web of Science ID 000352540800010

  • Plasma factor VII-activating protease antigen levels and activity are increased in ischemic stroke. Journal of thrombosis and haemostasis : JTH Hanson, E., Kanse, S. M., Joshi, A., Jood, K., Nilsson, S., Blomstrand, C., Jern, C. 2012; 10 (5): 848-56

    Abstract

    Factor VII-activating protease (FSAP) is a recently discovered plasma protease with a role in the regulation of hemostasis and vascular remodeling processes. Higher levels and activity of FSAP have been reported in patients with deep vein thrombosis, but there are no data on plasma FSAP in ischemic stroke (IS).To investigate whether FSAP antigen levels and activity are associated with IS and/or etiologic subtypes of IS.To assess the potential association between FSAP and IS, plasma FSAP antigen levels and activity were measured in 600 consecutive IS patients and 600 population-based controls from the case-control study the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Blood sampling was performed in the acute phase and 3 months after the index stroke. FSAP was also investigated at the genetic level by genotyping of 33 single-nucleotide polymorphisms.Increased FSAP antigen level and activity, at both time-points, were independently associated with IS. Subtype analysis revealed similar associations for both FSAP measures, at both time-points, in all main IS subtypes. FSAP genotypes showed association with both FSAP plasma measurements, but not with IS.Increased plasma FSAP antigen levels and activity were associated with IS and all main etiologic subtypes, suggesting a possible role for FSAP in the pathophysiology of IS, irrespective of the underlying etiology.

    View details for DOI 10.1111/j.1538-7836.2012.04692.x

    View details for PubMedID 22409238

  • Murine aldo-keto reductase family 1 subfamily B: identification of AKR1B8 as an ortholog of human AKR1B10. Biological chemistry Joshi, A., Rajput, S., Wang, C., Ma, J., Cao, D. 2010; 391 (12): 1371-8

    Abstract

    Aldo-keto reductase family 1 member B10 (AKR1B10), over-expressed in multiple human cancers, might be implicated in cancer development and progression via detoxifying cytotoxic carbonyls and regulating fatty acid synthesis. In the present study, we investigated the ortholog of AKR1B10 in mice, an ideal modeling organism greatly contributing to human disease investigations. In the mouse, there are three aldo-keto reductase family 1 subfamily B (AKR1B) members, i.e., AKR1B3, AKR1B7, and AKR1B8. Among them, AKR1B8 has the highest similarity to human AKR1B10 in terms of amino acid sequence, computer-modeled structures, substrate spectra and specificity, and tissue distribution. More importantly, similar to human AKR1B10, mouse AKR1B8 associates with murine acetyl-CoA carboxylase-? and mediates fatty acid synthesis in colon cancer cells. Taken together, our data suggest that murine AKR1B8 is the ortholog of human AKR1B10.

    View details for DOI 10.1515/BC.2010.144

    View details for PubMedID 21087085

  • TGF-beta signaling, tumor microenvironment and tumor progression: the butterfly effect. Frontiers in bioscience (Landmark edition) Joshi, A., Cao, D. 2010; 15: 180-94

    Abstract

    Transforming growth factor-beta (TGF-beta) signals through receptor serine/threonine kinases and intracellular Smad effectors, regulating numerous epithelial cell processes. TGF-beta plays a crucial role in the cancer initiation and progression through tumor cell autonomous signaling and interactions with tumor microenvironment, but is featured with a butterfly effect upon the stages of tumorigenesis. TGF-beta signaling acts as a suppressor of epithelial cell tumorigenesis at early stages, but promotes tumor progression by enhancing migration, invasion, and survival of the tumor cells during the later stages. TGF-beta signaling also cross-talks with other cell survival signaling pathways. Tumor microenvironment contains many distinct cell types, which substantially influences the tumor cell growth and survival, and the invasion and metastasis. TGF-beta in the microenvironment, produced by cancer and/or stromal cells, is high and negatively correlates with disease progression and patient prognosis. Therefore, TGF-beta may affect tumor progression by multiple mechanisms in addition to its direct action on tumor cells, and the diversities of TGF-beta signaling in tumors imply a need for caution to TGF-beta-targeted strategies of tumor prevention and/or therapeutics.

    View details for PubMedID 20036814

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