I am a postdoctoral researcher from Tehran, Iran. I joined Dr. Shirit Einav's lab in September 2021. The focus of my research is on screening, characterization, and enhancement of inhibitors of Numb-Associated Kinases (NAK) and lipid kinases which are involved in the viral life-cycle of pathogens such as Dengue virus (DENV), Venezuelan Equine Encephalitis Virus (VEEV) and SARS-CoV-2 with the hope of finding broad spectrum antiviral chemicals. I am also interested in discovering the targets/substrates for these kinases and their mechanism of action during viral infections.

My PhD dissertation under Dr. Stephanie Seveau's supervision at The Ohio State University was focused on the role of fetal placental macrophages in mother-to-fetus transmission of listeriosis. My master’s thesis at Qazvin University of Medical Sciences in Qazvin, Iran, was on a modified derivative of rotavirus toxin NSP4 as a candidate for vaccine production. I enjoy doing translational research that can be used as a stepping stone toward development of therapeutics to battle human diseases.
My hobbies are: Learning foreign languages, cooking, traveling, exploring food from different cultures, and inventing new cocktails with tequila!

Fun fact: To do research at Stanford, I moved by driving 2,500 miles across the country from Columbus, Ohio to San Jose, California, and had the greatest road trip of my life!

Honors & Awards

  • NIH-MMPC Outstanding Young Scientist Award, NIH through 2019 Midwest Microbial Pathogenesis Conference (2019)
  • Hodges Family Legacy Trainee Travel Award for Infectious Diseases, Department of Infection and Immunity, The Ohio State University, Columbus, Ohio (2019)

Boards, Advisory Committees, Professional Organizations

  • Member, The American Association of Immunologists (2019 - Present)
  • Member, United States Holocaust Memorial Museum (2019 - Present)
  • Member, American Heart Association (2019 - 2020)
  • Member, The American Society for Cell Biology (2018 - 2018)
  • Member, American Society for Microbiology (2017 - Present)
  • Secretary, Microbial Infection and Immunity Graduate Student Society (MIIGSS), The Ohio State University (2017 - 2019)
  • Member, MAHAK Society to Support Children Suffering from Cancer (2013 - 2016)

Professional Education

  • PhD, The Ohio State University, Microbiology (2021)
  • MS, Qazvin University of Medical Sciences, Medical Biotechnology (2014)
  • BS, University of Tehran, Microbiology (2011)

Stanford Advisors

Lab Affiliations

All Publications

  • The cargo adaptor protein CLINT1 is phosphorylated by the Numb-associated kinase BIKE and mediates dengue virus infection. The Journal of biological chemistry Schor, S., Pu, S., Nicolaescu, V., Azari, S., Koivomagi, M., Karim, M., Cassonnet, P., Saul, S., Neveu, G., Yueh, A., Demeret, C., Skotheim, J. M., Jacob, Y., Randall, G., Einav, S. 2022: 101956


    The signaling pathways and cellular functions regulated by the four Numb-associated kinases (NAKs) are largely unknown. We previously reported that AAK1 and GAK control intracellular trafficking of RNA viruses, and recently revealed a requirement for BIKE in early and late stages of dengue virus (DENV) infection. However, the downstream targets phosphorylated by BIKE in this process have not yet been identified. Here, to identify BIKE substrates, we conducted a barcode fusion genetics-yeast two-hybrid screen and retrieved publicly available data generated via affinity-purification mass spectrometry. We subsequently validated 19 of 47 putative BIKE interactors using mammalian cell-based protein-protein interaction assays. We found that CLINT1, a cargo-specific adaptor implicated in bidirectional Golgi-to-endosome trafficking, emerged as a predominant hit in both screens. Our experiments indicated that BIKE catalyzes phosphorylation of a threonine 294 (T294) CLINT1 residue both in vitro and in cell culture. Our findings revealed that CLINT1 phosphorylation mediates its binding to the DENV nonstructural 3 protein and subsequently promotes DENV assembly and egress. In addition, using live-cell imaging we revealed that CLINT1 cotraffics with DENV particles and is involved in mediating BIKE's role in DENV infection. Finally, our data suggest that additional cellular BIKE interactors implicated in the host immune and stress responses and the ubiquitin proteasome system might also be candidate phosphorylation substrates of BIKE. In conclusion, these findings reveal cellular substrates and pathways regulated by the understudied NAK enzyme BIKE, a mechanism for CLINT1 regulation, and control of DENV infection via BIKE signaling, with potential implications for cell biology, virology, and host-targeted antiviral design.

    View details for DOI 10.1016/j.jbc.2022.101956

    View details for PubMedID 35452674

  • Human Placental Trophoblasts Infected by Listeria monocytogenes Undergo a Pro-Inflammatory Switch Associated With Poor Pregnancy Outcomes. Frontiers in immunology Johnson, L. J., Azari, S., Webb, A., Zhang, X., Gavrilin, M. A., Marshall, J. M., Rood, K., Seveau, S. 2021; 12: 709466


    The placenta controls the growth of the fetus and ensures its immune protection. Key to these functions, the syncytiotrophoblast (SYN) is a syncytium formed by fusion of underlying mononuclear trophoblasts. The SYN covers the placental surface and is bathed in maternal blood to mediate nutritional and waste exchanges between the mother and fetus. The bacterial pathogen Listeria monocytogenes breaches the trophoblast barrier and infects the placental/fetal unit resulting in poor pregnancy outcomes. In this work, we analyzed the L. monocytogenes intracellular lifecycle in primary human trophoblasts. In accordance with previous studies, we found that the SYN is 20-fold more resistant to infection compared to mononuclear trophoblasts, forming a protective barrier to infection at the maternal interface. We show for the first time that this is due to a significant reduction in L. monocytogenes uptake by the SYN rather than inhibition of the bacterial intracellular division or motility. We here report the first transcriptomic analysis of L. monocytogenes-infected trophoblasts (RNA sequencing). Pathway analysis showed that infection upregulated TLR2, NOD-like, and cytosolic DNA sensing pathways, as well as downstream pro-inflammatory circuitry (NF-κB, AP-1, IRF4, IRF7) leading to the production of mediators known to elicit the recruitment and activation of maternal leukocytes (IL8, IL6, TNFα, MIP-1). Signature genes associated with poor pregnancy outcomes were also upregulated upon infection. Measuring the release of 54 inflammatory mediators confirmed the transcriptomic data and revealed sustained production of tolerogenic factors (IL-27, IL-10, IL-1RA, TSLP) despite infection. Both the SYN and mononuclear trophoblasts produced cytokines, but surprisingly, some cytokines were predominantly produced by the SYN (IL-8, IL-6) or by non-fused trophoblasts (TNFα). Collectively, our data support that trophoblasts act as placental gatekeepers that limit and detect L. monocytogenes infection resulting in a pro-inflammatory response, which may contribute to the poor pregnancy outcomes if the pathogen persists.

    View details for DOI 10.3389/fimmu.2021.709466

    View details for PubMedID 34367171

    View details for PubMedCentralID PMC8346206

  • Hofbauer Cells Spread Listeria monocytogenes among Placental Cells and Undergo Pro-Inflammatory Reprogramming while Retaining Production of Tolerogenic Factors. mBio Azari, S., Johnson, L. J., Webb, A., Kozlowski, S. M., Zhang, X., Rood, K., Amer, A., Seveau, S. 2021; 12 (4): e0184921


    Pregnant women are highly susceptible to infection by the bacterial pathogen Listeria monocytogenes, leading to miscarriage, premature birth, and neonatal infection. L. monocytogenes is thought to breach the placental barrier by infecting trophoblasts at the maternal/fetal interface. However, the fate of L. monocytogenes within chorionic villi and how infection reaches the fetus are unsettled. Hofbauer cells (HBCs) are fetal placental macrophages and the only leukocytes residing in healthy chorionic villi, forming a last immune barrier protecting fetal blood from infection. Little is known about the HBCs' antimicrobial responses to pathogens. Here, we studied L. monocytogenes interaction with human primary HBCs. Remarkably, despite their M2 anti-inflammatory phenotype at basal state, HBCs phagocytose and kill non-pathogenic bacteria like Listeria innocua and display low susceptibility to infection by L. monocytogenes. However, L. monocytogenes can exploit HBCs to spread to surrounding placental cells. Transcriptomic analyses by RNA sequencing revealed that HBCs undergo pro-inflammatory reprogramming upon L. monocytogenes infection, similarly to macrophages stimulated by the potent M1-polarizing agents lipopolysaccharide (LPS)/interferon gamma (IFN-γ). Infected HBCs also express pro-inflammatory chemokines known to promote placental infiltration by maternal leukocytes. However, HBCs maintain the expression of a collection of tolerogenic genes and secretion of tolerogenic cytokines, consistent with their tissue homeostatic role in prevention of fetal rejection. In conclusion, we propose a previously unrecognized model in which HBCs promote the spreading of L. monocytogenes among placental cells and transition to a pro-inflammatory state likely to favor innate immune responses, while maintaining the expression of tolerogenic factors known to prevent maternal anti-fetal adaptive immunity. IMPORTANCE Infection of the placental/fetal unit by the facultative intracellular pathogen Listeria monocytogenes results in severe pregnancy complications. Hofbauer cells (HBCs) are fetal macrophages that play homeostatic anti-inflammatory functions in healthy placentas. HBCs are located in chorionic villi between the two cell barriers that protect fetal blood from infection: trophoblast cells at the maternal interface (in contact with maternal blood), and fetal endothelial cells at the fetal interface (in contact with fetal blood). As the only leukocytes residing in chorionic villi, HBCs form a critical immune barrier protecting the fetus from infection. Here, we show that although HBCs display low susceptibility to L. monocytogenes, the bacterium still replicates intracellularly and can spread to other placental and fetal cells. We propose that HBCs are permissive to L. monocytogenes transplacental propagation and can repolarize toward a pro-inflammatory phenotype upon infection. However, consistent with their placental homeostatic functions, repolarized HBCs maintain the expression of tolerogenic factors known to prevent maternal anti-fetal adaptive immunity, at least at early stages of infection.

    View details for DOI 10.1128/mBio.01849-21

    View details for PubMedID 34399615

    View details for PubMedCentralID PMC8406333

  • Higher Expression Level and Lower Toxicity of Genetically Spliced Rotavirus NSP4 in Comparison to the Full-Length Protein in E. coli. Iranian journal of biotechnology Sahmani, M., Azari, S., Tebianian, M., Gheibi, N., Pourasgari, F. 2016; 14 (2): 50-57


    Rotavirus group A (RVA) is recognized as a major cause of severe gastroenteritis in children and new-born animals. Nonstructural protein 4 (NSP4) is responsible for the enterotoxic activity of these viruses in the villus epithelial cells. Amino acids 114-135 of NSP4 are known to form the diarrhea-inducing region of this viral enterotoxin. Therefore, developing an NSP4 lacking the enterotoxin domain could result in the introduction of a new subunit vaccine against rotaviruses in both humans and animals.The aim of this study is the evaluation of rotavirus A NSP4 expression in E. coli expression system before and after removal of the diarrhea-inducing domain, which is the first step towards further immunological studies of the resulting protein.Splicing by overlap extension (SOEing) PCR was used to remove the diarrhea-inducing sequence from the NSP4 cDNA. Both the full-length (FL-NSP4) and the spliced (S-NSP4) cDNA amplicons were cloned into pET-32c and pGEX-6P-2. Expression levels of the recombinant proteins were evaluated in E. coli BL21 (DE3) by Western blot analysis. In addition, the toxicity of pET plasmids bearing the S-NSP4 and FL-NSP4 fragments was investigated by plasmid stability test.For FL-NSP4, protein expression was detected for the strain containing the pGEX:FL-NSP4 plasmid, but not for the strain carrying pET:FL-NSP4. Hourly sampling up to 3 h showed that the protein production decreased by time. In contrast, expression of S-NSP4 was detected for pET:S-NSP4 strain, but not for pGEX:S-NSP4. Plasmid stability test showed that pET:S-NSP4 recombinant plasmid was almost stable, while pET:FL-NSP4 was unstable.This is the first report of production of rotavirus NSP4 lacking the diarrhea-inducing domain (S-NSP4). SNSP4 shows less toxicity in this expression system and potentially could be a promising goal for rotavirus immunological and vaccine studies in the future.

    View details for DOI 10.15171/ijb.1233

    View details for PubMedID 28959326

    View details for PubMedCentralID PMC5435032