Innate immune pathways in cerebrovascular disease
Our lab explores the role of the innate immune system in damage and repair following ischemic and hemorrhagic insults to the brain. We focus on neurosurgical diseases including aneurysmal subarachnoid hemorrhage, ischemic and hemorrhagic stroke, and subdural hemorrhage.
Immune drivers of secondary injury following cerebral aneurysm rupture
Subarachnoid hemorrhage (SAH) caused by a ruptured aneurysm is a significant source of morbidity and mortality worldwide and has a case-fatality of 27-44%. Early acute brain injury occurs from elevated intracranial pressure and a subsequent drop of cerebral perfusion in the very instant of the bleeding leading to death in 25% of cases. Secondary brain injury is an important potentially preventable cause of poor outcome in SAH patients. The knowledge gaps that we aim to address include:
- the effect of subarachnoid blood on the CSF-brain interface and the corresponding parenchymal immune response
- the role of meningeal innate immune cells in secondary injury
- the role of the acute intracranial pressure spike in triggering the initial immune response
Development of therapeutics for intraarterial immunomodulation for chronic subdural hemorrhage
Chronic subdural hematoma (cSDH) is one of the most common neurosurgical conditions. Depending on severity, treatment includes conservative management, surgical evacuation, and middle meningeal artery (MMA) embolization. However, recurrence rate with poor functional outcome is high. The popularization of endovascular access to the MMA for embolization provides an excellent opportunity to consider direct local administration of therapeutics to the dura and subdural membranes to target the cSDH pathogenesis. Our apporach consists of:
- Creation of a rodent model of cSDH using transcranial ultrasound-mediated dural vessel disrupition.
- Characterization of dominant molecular pathways and cell-specific interactions that drive cSDH to identify therapeutic targets.
- Rapid screening of small molecules and antibodies via transcranial administration to the mouse dura.
Meet the Principal Investigator
Panagiotis Mastorakos M.D., Ph.D.
Dr. Panos Mastorakos was raised in Athens, Greece. He pursued his education in medicine, earning both a medical degree and a doctoral degree in neurosurgery at the University of Athens School of Health Sciences. His medical journey continued with a neurosurgery residency at the National Institutes of Health and the University of Virginia. During this period, he also received advanced training in endovascular neurosurgery. Subsequently, he further honed his expertise by completing a cerebrovascular fellowship at Thomas Jefferson University. As a cerebrovascular neurosurgeon, his primary clinical focus centers on the management of vascular lesions, ischemic, and hemorrhagic stroke.
In addition to his clinical work, Panos is deeply committed to research. He initially pursued basic/translational research training at Johns Hopkins University under the mentorship of Dr. Justin Hanes and Dr. Rangaramanujam Kannan. His research efforts were primarily directed towards optimizing the delivery of nanotherapeutics to the central nervous system. Later on, his research interests expanded to encompass secondary injuries associated with cerebrovascular diseases. To delve into this field, he sought training in neuroimmunology under the guidance of Dr. Dorian McGavern at the National Institutes of Health. His research in this area focused on understanding the responses of myeloid cells following hemorrhagic stroke, utilizing a combination of immunology techniques to elucidate the interplay between invading monocytes and microglia and their roles in acute injury and repair.
In 2023, Panos joined UT Southwestern as an Assistant Professor in the Departments of Neurological Surgery and the O'Donnell Jr. Brain Institute. His current research is concentrated on developing treatments for ischemic and hemorrhagic insults to the brain. He is particularly interested in unraveling the immune response triggered by acute intracranial pressure fluctuations in the context of aneurysm rupture. Furthermore, he is dedicated to leveraging targeted immunomodulation to enhance recovery from ischemic stroke.
Featured Publications
Antimicrobial immunity impedes CNS vascular repair following brain injury. Mastorakos P, Russo MV, Zhou T, Johnson K, McGavern DB. Nature Immunology. (2021) PMID: 34556874
Temporally distinct myeloid cell responses mediate damage and repair after cerebrovascular injury. Mastorakos P, Mihelson N, Burks S, Latour L, Frank J, McGavern D. Nature Neuroscience (2021) PMID: 33462481
The Anatomy and Immunology of Vasculature in the Central Nervous System. Mastorakos P, McGavern D. Science Immunology. (2019) PMID: 31300479
Contact us
Email: panagiotis.mastorakos@utsouthwestern.edu
Phone Number: 214-648-2980
Lab Address
Peter O'Donnell Jr. Brain Institute
6124 Harry Hines Blvd, NS9.320AA
Dallas, TX 75390
Office Address
Peter O'Donnell Jr. Brain Institute
6124 Harry Hines Blvd, NS9.310
Dallas, TX 75390
Mailing Address
UT Southwestern Medical Center
5323 Harry Hines Blvd.
Dallas, TX 75390-8855
Get in touch
We are always looking for highly motivated people to join our research team or collaborate with us. We are commited to better understanding the innate immune pathways implicated in cerebrovascular diseases. If you are interested in joining our team email a cover letter and CV to Dr. Mastorakos.