Person:
Khoury, Joseph

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Khoury

First Name

Joseph

Name

Khoury, Joseph
Author's Publications: search.filters.isAuthorOfPublication.2788d31d-5d1c-4597-a45f-0b8cf6313611

Search Results

Now showing 1 - 4 of 4
  • Thumbnail Image
    Publication
    The scavenger receptor SCARF1 mediates apoptotic cell clearance and prevents autoimmunity
    (2013) Ramirez-Ortiz, Zaida; Pendergraft, William F.; Prasad, Amit; Byrne, Michael H.; Iram, Tal; Blanchette, Christopher J.; Luster, Andrew; Hacohen, Nir; Khoury, Joseph; Means, Terry K.
    Clearance of apoptotic cells is critical for control of tissue homeostasis however the full range of receptor(s) on phagocytes responsible for recognition of apoptotic cells remains to be identified. Here we show that dendritic cells (DCs), macrophages and endothelial cells use scavenger receptor type F family member 1 (SCARF1) to recognize and engulf apoptotic cells via C1q. Loss of SCARF1 impairs uptake of apoptotic cells. Consequently, in SCARF1-deficient mice, dying cells accumulate in tissues leading to a lupus-like disease with the spontaneous generation of autoantibodies to DNA-containing antigens, immune cell activation, dermatitis and nephritis. The discovery of SCARF1 interactions with C1q and apoptotic cells provides insights into molecular mechanisms involved in maintenance of tolerance and prevention of autoimmune disease.
  • Thumbnail Image
    Publication
    The Microglial Sensome Revealed by Direct RNA Sequencing
    (2013) Hickman, Suzanne E.; Kingery, Nathan D.; Ohsumi, Toshiro; Borowsky, Mark L; Wang, Li-chong; Means, Terry K.; Khoury, Joseph
    Microglia, the principal neuroimmune sentinels of the brain, continuously sense changes in their environment and respond to invading pathogens, toxins and cellular debris. Microglia exhibit plasticity and can assume neurotoxic or neuroprotective priming states that determine their responses to danger. We used direct RNA sequencing, without amplification or cDNA synthesis, to determine the quantitative transcriptomes of microglia of healthy adult and aged mice. We validated our findings by fluorescent dual in-situ hybridization, unbiased proteomic analysis and quantitative PCR. We report here that microglia have a distinct transcriptomic signature and express a unique cluster of transcripts encoding proteins for sensing endogenous ligands and microbes that we term the “sensome”. With aging, sensome transcripts for endogenous ligand recognition are downregulated, whereas those involved in microbe recognition and host defense are upregulated. In addition, aging is associated with an overall increase in expression of microglial genes involved in neuroprotection.
  • Thumbnail Image
    Publication
    TREML4 amplifies TLR7-mediated signaling during antiviral responses and autoimmunity
    (2015) Ramirez-Ortiz, Zaida; Prasad, Amit; Griffith, Jason; Pendergraft, William F.; Cowley, Glenn S.; Root, David E.; Tai, Melissa; Luster, Andrew; Khoury, Joseph; Hacohen, Nir; Means, Terry K.
    The genes and pathways that fine-tune TLR7-mediated innate inflammatory responses remain to be fully elucidated. Using an unbiased genome-scale shRNA screen, we identified the receptor TREML4 as an essential positive regulator of TLR7 signaling. Macrophages from Treml4–/– mice were hyporesponsive to TLR7 agonists and failed to produce type I interferon due to impaired phosphorylation of the transcription factor STAT1 by the MAP kinase p38 and decreased recruitment of MyD88 to TLR7. TREML4 deficiency reduced production of inflammatory cytokines and autoantibodies in SLE-prone MRL/lpr mice and inhibited the antiviral immune response to influenza. Our data identify TREML4 as a positive regulator of TLR7 signaling and provide insight into the molecular mechanisms that control antiviral immunity and the development of autoimmunity.
  • Thumbnail Image
    Publication
    Shorter Telomeres May Mark Early Risk of Dementia: Preliminary Analysis of 62 Participants from the Nurses' Health Study
    (Public Library of Science, 2008) van Oijen, Marieke; Irizarry, Michael C.; Grodstein, Francine; Rosas, Herminia; Hyman, Bradley; Growdon, John; De Vivo, Immaculata; Khoury, Joseph
    Background: Dementia takes decades to develop, and effective prevention will likely require early intervention. Thus, it is critical to identify biomarkers of preclinical disease, allowing targeting of high-risk subjects for preventive efforts. Since telomeres shorten with age and oxidative stress, both of which are important contributors to the onset of dementia, telomere length might be a valuable biomarker. Methodology/Principal Findings: Among 62 participants of the Nurses' Health Study, we conducted neurologic evaluations, including patient and caregiver interviews, physical exam, neurologic exam, and neuropsychologic testing. We also conducted magnetic resonance imaging (MRI) in a sample of 29 of these women. In these preliminary data, after adjustment for numerous health and lifestyle factors, we found that truncated telomeres in peripheral blood leukocytes segregate with preclinical dementia states, including mild cognitive impairment (MCI); the odds of MCI were 12-fold higher (odds ratio = 12.00, 95% confidence interval 1.24–116.5) for those with shorter telomere length compared to longer telomere length. In addition, decreasing telomere length was strongly related to decreasing hippocampal volume (p = 0.038). Conclusions: These preliminary data suggest that telomere length may be a possible early marker of dementia risk, and merits further study in large, prospective investigations.