Browsing by Author "Mohammed, Muddasir"

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    JAK3 restrains inflammatory responses and protects against periodontal disease through Wnt3a signaling
    (Wiley, 2020-07) Lü, Lanhai; Yakoumatos, Lan; Ren, Junling; Duan, Xiaoxian; Zhou, Huaxin; Gu, Zhen; Mohammed, Muddasir; Uriarte, Silvia M.; Liang, Shuang; Scott, David A.; Lamont, Richard J.; Wang, Huizhi; Medicine, School of Medicine
    Homeostasis between pro- and anti- inflammatory responses induced by bacteria is critical for the maintenance of health. In the oral cavity, proinflammatory mechanisms induced by pathogenic bacteria are well-established; however, the anti-inflammatory responses that act to restrain innate responses remain poorly characterized. Here, we demonstrate that infection with the periodontal pathogen P. gingivalis enhances the activity of JAK3 in innate immune cells, and subsequently phospho-inactivates Nedd4-2, a ubiquitin E3 ligase. In turn, Wnt3 ubiquitination is decreased, while total protein levels are enhanced, leading to a reduction in proinflammatory cytokine levels. In contrast, JAK3 inhibition or Wnt3a robustly enhances NF-κB activity and the production of proinflammatory cytokines in P. gingivalis-stimulated innate immune cells. Moreover, using gain- and loss-of-function approaches, we demonstrate that downstream molecules of Wnt3a signaling, including Dvl3 and β-catenin, are responsible for the negative regulatory role of Wnt3a. In addition, using an in vivo P. gingivalis-mediated periodontal disease model, we show that JAK3 inhibition enhances infiltration of inflammatory cells, reduces expression of Wnt3a and Dvl3 in P. gingivalis-infected gingival tissues, and increases disease severity. Together, our results reveal a new anti-inflammatory role for JAK3 in innate immune cells and show that the underlying signaling pathway involves Nedd4-2-mediated Wnt3a ubiquitination.
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    Knowing Me, Knowing You, Bringing International and Traditional Dental Students Together
    (American Dental Education Association, 2022-10-06) Cho, Sopanis; Mohammed, Muddasir; Stone, Sean M.
    The International Dentist Program (IDP) matriculates dentists graduated from outside the United States through an accelerated 30-month version of the traditional DDS program so that they can take board examinations and attain a U.S. DDS. As much as possible, IDP students study with cohorts of students in the traditional DDS program. This can prove challenging, however, as IDP students represent myriad differences in education, training, culture, and life experiences. Because of this, the early portion of the IDP curriculum ensures that student preclinical and other skills are equilibrated to similar levels so that they can effectively merge with their peers from the traditional DDS program. IDP students’ matriculation is staggered from traditional DDS students and when they join them as classmates the D2s have already spent one and a half years together forging relationships and adjusting to being dental students. Because of this and their diverse backgrounds, IDP’s have reported significant challenges that can hopefully be addressed by changing the climate with a program of improved communication and events.