Bio

Bio


Department of Anatomy and Cellular Biology, Tufts University, Boston, MA
Ph.D. Cell, Molecular and Developmental Biology

Sept 2007-March 2013

Christian Brothers University, Memphis, TN
B.S. Biology (Minors: Chemistry and Psychology) summa cum laude

Jan 2005-May 2007

Honors & Awards


  • Sackler School Dean’s Award, Tufts University (2013)
  • Commencement Speaker, Sackler School of Graduate Biomedical Sciences, Tufts University (2013)
  • Society of Pediatric Research (SPR) Student Research Award, Pediatric Academic Societies / Society of Pediatric Research (2012)
  • Society of Developmental Biology Travel Award, Society of Developmental Biology (2011)

Professional Education


  • Bachelor of Science, Christian Brothers University (2007)
  • Doctor of Philosophy, Tufts University (2013)

Stanford Advisors


Publications

Journal Articles


  • miRNA regulated pathways in late stage murine lung development BMC DEVELOPMENTAL BIOLOGY Mujahid, S., Logvinenko, T., Volpe, M. V., Nielsen, H. C. 2013; 13

    Abstract

    MicroRNAs play important roles in regulating biological processes, including organ morphogenesis and maturation. However, little is known about specific pathways regulated by miRNA during lung development. Between the canalicular and saccular stages of the developing lung several important cellular events occur, including the onset of surfactant synthesis, microvascular remodeling and structural preparation for subsequent alveolarization. The miRNAs that are actively regulated, and the identity of their targets during this important developmental interval in the lung remain elusive.Using TLDA low density real-time PCR arrays, the expression of 376 miRNAs in male and female fetal mouse lungs of gestational days E15 - E18 were profiled. Statistical analyses identified 25 and 37 miRNAs that changed significantly between sexes and with gestation, respectively. In silico analysis using Ingenuity Pathway Analysis (IPA) identified specific pathways and networks known to be targets of these miRNAs which are important to lung development. Pathways that are targeted by sex regulated miRNAs include retinoin, IGFR1, Tp53 and Akt. Pathways targeted by gestation-regulated miRNAs include VEGFA and mediators of glucose metabolism.MiRNAs are differentially regulated across time and between sexes during the canalicular and saccular stages of lung development. Sex-associated differential miRNA expression may regulate the differences in structural and functional male and female lung development, as shown by networks generated using in silico analysis. These data provide a valuable resource to further enhance the understanding of miRNA control of lung development and maturation.

    View details for DOI 10.1186/1471-213X-13-13

    View details for Web of Science ID 000318911800001

    View details for PubMedID 23617334

  • MiR-221 and miR-130a Regulate Lung Airway and Vascular Development PLOS ONE Mujahid, S., Nielsen, H. C., Volpe, M. V. 2013; 8 (2)

    Abstract

    Epithelial-mesenchymal interactions play a crucial role in branching morphogenesis, but very little is known about how endothelial cells contribute to this process. Here, we examined how anti-angiogenic miR-221 and pro-angiogenic miR-130a affect airway and vascular development in the fetal lungs. Lung-specific effects of miR-130a and miR-221 were studied in mouse E14 whole lungs cultured for 48 hours with anti-miRs or mimics to miR-130a and miR-221. Anti-miR 221 treated lungs had more distal branch generations with increased Hoxb5 and VEGFR2 around airways. Conversely, mimic 221 treated lungs had reduced airway branching, dilated airway tips and decreased Hoxb5 and VEGFR2 in mesenchyme. Anti-miR 130a treatment led to reduced airway branching with increased Hoxa5 and decreased VEGFR2 in the mesenchyme. Conversely, mimic 130a treated lungs had numerous finely arborized branches extending into central lung regions with diffusely localized Hoxa5 and increased VEGFR2 in the mesenchyme. Vascular morphology was analyzed by GSL-B4 (endothelial cell-specific lectin) immunofluorescence. Observed changes in airway morphology following miR-221 inhibition and miR-130a enhancement were mirrored by changes in vascular plexus formation around the terminal airways. Mouse fetal lung endothelial cells (MFLM-91U) were used to study microvascular cell behavior. Mimic 221 treatment resulted in reduced tube formation and cell migration, where as the reverse was observed with mimic 130a treatment. From these data, we conclude that miR-221 and miR-130a have opposing effects on airway and vascular morphogenesis of the developing lung.

    View details for DOI 10.1371/journal.pone.0055911

    View details for Web of Science ID 000314660300044

    View details for PubMedID 23409087

  • Regulatory interactions between androgens, Hoxb5, and TGF ß signaling in murine lung development. BioMed research international Volpe, M. V., Ramadurai, S. M., Mujahid, S., Vong, T., Brandao, M., Wang, K. T., Pham, L. D., Nielsen, H. C. 2013; 2013: 320249-?

    Abstract

    Androgens enhance airway branching but delay alveolar maturation contributing to increased respiratory morbidity in prematurely born male infants. Hoxb5 protein positively regulates airway branching in developing lung. In other organs, androgen regulation intersects with Hox proteins and TGF β -SMAD signaling, but these interactions have not been studied in the lung. We hypothesized that androgen alteration of airway branching early in lung development requires Hoxb5 expression and that these androgen-Hoxb5 interactions occur partially through regional changes in TGF β signaling. To evaluate acute effects of androgen and TGF β on Hoxb5, E11 whole fetal mouse lungs were cultured with dihydrotestosterone (DHT) with/without Hoxb5 siRNA or TGF β inhibitory antibody. Chronic in utero DHT exposure was accomplished by exposing pregnant mice to DHT (subcutaneous pellet) from E11 to E18. DHT's ability to enhance airway branching and alter phosphorylated SMAD2 cellular localization was partially dependent on Hoxb5. Hoxb5 inhibition also changed the cellular distribution of SMAD7 protein. Chronic in utero DHT increased Hoxb5 and altered SMAD7 mesenchymal localization. TGF β inhibition enhanced airway branching, and Hoxb5 protein cellular localization was more diffuse. We conclude that DHT controls lung airway development partially through modulation of Hoxb5 protein expression and that this level of regulation involves interactions with TGF β signaling.

    View details for DOI 10.1155/2013/320249

    View details for PubMedID 24078914

  • Presenilin-1 processing of ErbB4 in fetal type II cells is necessary for control of fetal lung maturation BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH Hoeing, K., Zscheppang, K., Mujahid, S., Murray, S., Volpe, M. V., Dammann, C. E., Nielsen, H. C. 2011; 1813 (3): 480-491

    Abstract

    Maturation of pulmonary fetal type II cells to initiate adequate surfactant production is crucial for postnatal respiratory function. Little is known about specific mechanisms of signal transduction controlling type II cell maturation. The ErbB4 receptor and its ligand neuregulin (NRG) are critical for lung development. ErbB4 is cleaved at the cell membrane by the γ-secretase enzyme complex whose active component is either presenilin-1 (PSEN-1) or presenilin-2. ErbB4 cleavage releases the 80kDa intracellular domain (4ICD), which associates with chaperone proteins such as YAP (Yes-associated protein) and translocates to the nucleus to regulate gene expression. We hypothesized that PSEN-1 and YAP have a development-specific expression in fetal type II cells and are important for ErbB4 signaling in surfactant production. In primary fetal mouse E16, E17, and E18 type II cells, PSEN-1 and YAP expression increased at E17 and E18 over E16. Subcellular fractionation showed a strong cytosolic and a weaker membrane location of both PSEN-1 and YAP. This was enhanced by NRG stimulation. Co-immunoprecipitations showed ErbB4 associated separately with PSEN-1 and with YAP. Their association, phosphorylation, and co-localization were induced by NRG. Confocal immunofluorescence and nuclear fractionation confirmed these associations in a time-dependent manner after NRG stimulation. Primary ErbB4-deleted E17 type II cells were transfected with a mutant ErbB4 lacking the γ-secretase binding site. When compared to transfection with wild-type ErbB4, the stimulatory effect of NRG on surfactant protein mRNA expression was lost. We conclude that PSEN-1 and YAP have crucial roles in ErbB4 signal transduction during type II cell maturation.

    View details for DOI 10.1016/j.bbamcr.2010.12.017

    View details for Web of Science ID 000288628600012

    View details for PubMedID 21195117

  • Subtype-specific residues involved in ligand activation of the endothelial differentiation gene family lysophosphatidic acid receptors JOURNAL OF BIOLOGICAL CHEMISTRY Valentine, W. J., Fells, J. I., Perygin, D. H., Mujahid, S., Yokoyama, K., Fujiwara, Y., Tsukahara, R., Van Brocklyn, J. R., Parrill, A. L., Tigyi, G. 2008; 283 (18): 12175-12187

    Abstract

    Lysophosphatidic acid (LPA) is a ligand for three endothelial differentiation gene family G protein-coupled receptors, LPA(1-3). We performed computational modeling-guided mutagenesis of conserved residues in transmembrane domains 3, 4, 5, and 7 of LPA(1-3) predicted to interact with the glycerophosphate motif of LPA C18:1. The mutants were expressed in RH7777 cells, and the efficacy (E(max)) and potency (EC(50)) of LPA-elicited Ca(2+) transients were measured. Mutation to alanine of R3.28 universally decreased both the efficacy and potency in LPA(1-3) and eliminated strong ionic interactions in the modeled LPA complexes. The alanine mutation at Q3.29 decreased modeled interactions and activation in LPA(1) and LPA(2) more than in LPA(3). The mutation W4.64A had no effect on activation and modeled LPA interaction of LPA(1) and LPA(2) but reduced the activation and modeled interactions of LPA(3). The R5.38A mutant of LPA(2) and R5.38N mutant of LPA(3) showed diminished activation by LPA; however, in LPA(1) the D5.38A mutation did not, and mutation to arginine enhanced receptor activation. In LPA(2), K7.36A decreased the potency of LPA; in LPA(1) this same mutation increased the E(max). In LPA(3), R7.36A had almost no effect on receptor activation; however, the mutation K7.35A increased the EC(50) in response to LPA 10-fold. In LPA(1-3), the mutation Q3.29E caused a modest increase in EC(50) in response to LPA but caused the LPA receptors to become more responsive to sphingosine 1-phosphate (S1P). Surprisingly micromolar concentrations of S1P activated the wild type LPA(2) and LPA(3) receptors, indicating that S1P may function as a weak agonist of endothelial differentiation gene family LPA receptors.

    View details for DOI 10.1074/jbc.M708847200

    View details for Web of Science ID 000255340000034

    View details for PubMedID 18316373

Stanford Medicine Resources: