Philadelphia University + Thomas Jefferson University

Hooper, D Craig

< Back

Profile

dch101

D. Craig Hooper, PhD

Contact Dr. Hooper

1020 Locust Street
Room 452
Philadelphia, PA 19107

(215) 503-1774
(215) 923-7745 fax

Research and Clinical Interests

The principle research area of the Hooper laboratory is CNS immunity and, particularly, the balance between protective and destructive neuroinflammatory processes.  CNS tissues are protected from immune mechanisms by the blood-brain barrier (BBB) and a major focus of the lab is on mechanisms that modulate BBB integrity and how these impact protective versus pathological CNS inflammatory and neurodegenerative conditions. Important questions are how does the therapeutic delivery of immune effectors across the BBB during virus clearance differ from pathological immune cell invasion into the CNS parenchyma and how are these processes regulated? We were the first to show that peroxynitrite-dependent radicals open the BBB during a CNS inflammatory response and that the sources of these radicals differ between pathological and therapeutic immune cell invasion into CNS tissues. Our current projects are directed at understanding the mechanisms through which therapeutic immune cells and molecules, such as lymphocytes and antibodies, are naturally delivered to CNS tissues during a CNS immune response such that these processes may be manipulated therapeutically for the treatment of neurotropic virus infection, neurodegenerative disease, and brain cancer. For example, we have discovered that the protective alterations in BBB function required for immune effector infiltration into CNS tissues during the therapeutic clearance of attenuated rabies viruses are inhibited during infection with highly pathogenic rabies viruses. This enables pathogenic rabies viruses to evade immune clearance and cause a lethal infection despite eliciting strong anti-viral immune responses in the periphery. We are assessing various strategies to circumvent this block and deliver therapeutic reagents into the infected CNS tissues, approaches that will also be used to target immune effectors to CNS tumors. From the opposite perspective we are continuing our long-term studies of peroxynitrite-dependent radical inactivation as a means to maintain BBB integrity and prevent potentially pathological cells and factors from infiltrating into CNS tissues. We pioneered the approach of raising serum levels of urate, a natural peroxynitrite-dependent radical scavenger, for the treatment of CNS autoimmunity, a strategy that is the foundation of several clinical trials in multiple sclerosis (MS) and Parkinsons disease. Current studies are directed at understanding the pathways through which the peroxynitrite-dependent radicals inactivated by urate mediate their effects on the BBB and CNS tissues.

Publications

Most Recent Peer-Reviewed Publications

  1. Pharmacologic or Genetic Targeting of Glutamine Synthetase Skews Macrophages toward an M1-like Phenotype and Inhibits Tumor Metastasis
  2. Type 1 immune mechanisms driven by the response to infection with attenuated rabies virus result in changes in the immune bias of the tumor microenvironment and necrosis of mouse GL261 brain tumors
  3. Blockade of Glutamine Synthetase Enhances Inflammatory Response in Microglial Cells
  4. Human parechovirus and enterovirus initiate distinct CNS innate immune responses: Pathogenic and diagnostic implications
  5. Immune biomarkers of treatment failure for a patient on a phase i clinical trial of pembrolizumab plus radiotherapy
  6. Serum exosomes and cytokines promote a T-helper cell type 2 environment in the peripheral blood of glioblastoma patients
  7. T-bet is required for the rapid clearance of attenuated rabies virus from central nervous system tissue
  8. Acetylation of human mitochondrial citrate carrier modulates mitochondrial citrate/malate exchange activity to sustain NADPH production during macrophage activation
  9. Enhancement of glioma-specific immunity in mice by “NOBEL”, an insulin-like growth factor 1 receptor antisense oligodeoxynucleotide
  10. Glioblastoma exosomes and IGF-1R/AS-ODN are immunogenic stimuli in a translational research immunotherapy paradigm
  11. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ
  12. Expression of interferon gamma by a recombinant rabies virus strongly attenuates the pathogenicity of the virus via induction of type I interferon
  13. Differential host immune responses after infection with wild-type or lab-attenuated rabies viruses in dogs
  14. Use of advanced magnetic resonance imaging techniques in neuromyelitis optica spectrum disorder
  15. Limited brain metabolism changes differentiate between the progression and clearance of rabies virus
  16. Glioma grade is associated with the accumulation and activity of cells bearing M2 monocyte markers
  17. Intramuscular inoculation of mice with the live-attenuated recombinant rabies virus TriGAS results in a transient infection of the draining lymph nodes and a robust, long-lasting protective immune response against rabies
  18. Presence of Virus Neutralizing Antibodies in Cerebral Spinal Fluid Correlates with Non-Lethal Rabies in Dogs
  19. Aleuria Aurantia Lectin (AAL)-Reactive Immunoglobulin G Rapidly Appears in Sera of Animals following Antigen Exposure
  20. Temporal changes in innate immune signals in a rat model of alcohol withdrawal in emotional and cardiorespiratory homeostatic nuclei