个人简介
Ph.D. Pharmacology / Biochemistry
Baylor College of Medicine 1975
Molecular Genetics and Biochemistry
Cellular Molecular Biology and Physiology
Molecular Genetics/Cell Physiology
Host: Pathogen relationships, innate immune defenses against zoonotic viruses, adaptive immune defense, including humoral and cellular defenses, virus pathogenesis, neuropathogenesis, neuroimmunology, neurogenomics, therapeutics (drug discovery) and vaccine designs, rapid pathogen identification, high-throughput diagnostics, models of natural versus foreign host infection, FTIR spectroscopy, and high-content screeing.
Pathogen Interactions in Natural and Foreign (Zoonotic) Hosts During Nonhuman Primate Alphaherpesvirus Infections of Primary Target Cells and Within the Cells of Peripheral and Central Nervous Systems.
研究领域
The principal focus of our laboratory is to increase our understanding of the dynamic interactions between B virus (Macacine herpesvirus 1) and the natural and foreign hosts it infects. The earliest host responses to virus infection consist of innate defenses, which ultimately result in a directed adaptive defense responses of host cells. Viruses can redirect or block these responses effectively particularly when virus and host species have not had the opportunity to co-adapt together. When there has been little or no co-evolution, there is often a lack of orchestrated activity essential for survival of both the host and the virus or successful endosymbiotic relationship. Scientific investigators often focus on such viruses because they generally result in the demise of the infected host and the concomitant negative economic impacts caused by morbidities and loss of lives. B virus is studied in our laboratory as the model of a foreign versus natural host infections. We have similarly studied baboon reovirus, an agent discovered in our laboratory and found to be the etiologic agent of encephalitic disease in baboons from both captive colonies and in the wild. Understanding the mechanisms by which viruses invade the central nervous system and host actions that control this invasion serves to inform the rational design of successful intervention strategies for therapeutics and vaccines. Our early studies were designed to better understand B virus structure and identify differences between this unique zoonotic virus and its relatively innocuous alphaherpesvirus family members. B virus is the only member of the genus Herpesviridae that causes zoonotic infections, killing up to 80% of untreated humans. Fortunately zoonotic infection is rare, observed primarily in occupational settings where humans have close contact with macaques but when these infections occur our laboratory collects isolates and studies pathogenesis utilizing peri-mortem and post mortem samples to better understand the pathways utilized by B virus to invade the human brainstem in cases when therapeutic intervention fails. Our laboratory also provides laboratory support for survivors of B virus zoonosis, which ultimately informs the mechanisms responsible for latency and reactivation differences in natural versus foreign hosts. For much of our research we utilize primary cell culture models as well as small animal models of disease to better characterize cell:virus (host:pathogen) interactions, including innate and adaptive defenses that are recruited/redirected during the course of infection. For these studies we utilize co-cultivation techniques, real-time microscopy, and high-content intracellular screening technologies. Additionally, we continue to design and study enhanced strategies for early identification of infection in both humans and nonhuman primates and mechanisms by which zoonotic infections can be successfully treated/prevented because B virus is a grave occupational hazard in research facilities using macaque monkeys for biomedical research. Further, application of novel diagnostic technologies provide critical insight about the challenges of identifying zoonotic virus infections in which standard defenses often fail, ultimately making dependence on standard technologies doomed, e.g., seen in the SARS outbreak in the past decade. Our unique work has allowed us to discover new nonhuman primate alphaherpesviruses in langurs, mangabeys, baboon, and patas monkeys and has led to the identification of a potentially effective drug for treatment of late-stage B virus zoonosis. Our laboratory, in its clinical capacity, serves as the home of the National B Virus Resource Center, which provides global diagnostic support for detection of B virus zoonotic disease as well as for maintenance of specific pathogen-free macaque colonies in support of NIH’s SPF HIV/AIDS Animals Models, which enables active collaborations with a wide number of commercial, academic, nonprofit research laboratories, zoos, and wild-life preserves. This part of our laboratory provides 24/7/365 emergency diagnostic testing performed by registered medical technologists who are dedicated to providing state-of-the art, high-throughput diagnostics for viruses requiring BSL-3 and BSL-4 containment. The Viral Immunology Center is home of the only BSL4 laboratory on the campus of a public university that trains both undergraduate and graduate students to be the future leaders in studies of special pathogens requiring the highest levels of biocontainment.
近期论文
查看导师新发文章
(温馨提示:请注意重名现象,建议点开原文通过作者单位确认)
Safety and efficacy of dual-lead thalamic deep brain stimulation for patients with treatment-refractory multiple sclerosis tremor: a single-centre, randomised, single-blind, pilot trial.
Oliveria SF, Rodriguez RL, Bowers D, Kantor D, Hilliard JD, Monari EH, Scott BM, Okun MS, Foote KD.
Lancet Neurol. 2017 Jun 19. pii: S1474-4422(17)30166-7. doi: 10.1016/S1474-4422(17)30166-7. [Epub ahead of print]
Regulation of PI3K/Akt dependent apoptotic markers during b virus infection of human and macaque fibroblasts.
Vasireddi M, Hilliard JK.
PLoS One. 2017 May 30;12(5):e0178314. doi: 10.1371/journal.pone.0178314. eCollection 2017.
Targeting Alpha Toxin To Mitigate Its Lethal Toxicity in Ferret and Rabbit Models of Staphylococcus aureus Necrotizing Pneumonia.
Diep BA, Hilliard JJ, Le VT, Tkaczyk C, Le HN, Tran VG, Rao RL, Dip EC, Pereira-Franchi EP, Cha P, Jacobson S, Broome R, Cheng LI, Weiss W, Prokai L, Nguyen V, Stover CK, Sellman BR.
Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e02456-16. doi: 10.1128/AAC.02456-16. Print 2017 Apr.
B Virus (Macacine Herpesvirus 1) Divergence: Variations in Glycoprotein D from Clinical and Laboratory Isolates Diversify Virus Entry Strategies.
Patrusheva I, Perelygina L, Torshin I, LeCher J, Hilliard J.
J Virol. 2016 Sep 29;90(20):9420-32. doi: 10.1128/JVI.00799-16. Print 2016 Oct 15.
Critical Role of Alpha-Toxin and Protective Effects of Its Neutralization by a Human Antibody in Acute Bacterial Skin and Skin Structure Infections.
Le VT, Tkaczyk C, Chau S, Rao RL, Dip EC, Pereira-Franchi EP, Cheng L, Lee S, Koelkebeck H, Hilliard JJ, Yu XQ, Datta V, Nguyen V, Weiss W, Prokai L, O'Day T, Stover CK, Sellman BR, Diep BA.
Antimicrob Agents Chemother. 2016 Sep 23;60(10):5640-8. doi: 10.1128/AAC.00710-16. Print 2016 Oct.
138 Delayed Scalp Erosion After Deep Brain Stimulation Surgery: Incidence, Treatment, Outcomes, and Prevention.
Hilliard JD, Bona A, Vaziri S, Walz R, Okun MS, Foote KD.
Neurosurgery. 2016 Aug;63 Suppl 1:156. doi: 10.1227/01.neu.0000489708.21831.66.
Post-mortem Findings in Huntington's Deep Brain Stimulation: A Moving Target Due to Atrophy.
Vedam-Mai V, Martinez-Ramirez D, Hilliard JD, Carbunaru S, Yachnis AT, Bloom J, Keeling P, Awe L, Foote KD, Okun MS.
Tremor Other Hyperkinet Mov (N Y). 2016 Apr 27;6:372. doi: 10.7916/D8ZP462H. eCollection 2016.
Staphylococcus aureus α toxin potentiates opportunistic bacterial lung infections.
Cohen TS, Hilliard JJ, Jones-Nelson O, Keller AE, O'Day T, Tkaczyk C, DiGiandomenico A, Hamilton M, Pelletier M, Wang Q, Diep BA, Le VT, Cheng L, Suzich J, Stover CK, Sellman BR.
Sci Transl Med. 2016 Mar 9;8(329):329ra31. doi: 10.1126/scitranslmed.aad9922.