Panagiotis Mastorakos, M.D., Ph.D.

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Dr. Mastorakos is a cerebrovascular neurosurgeon with interest in elucidating the role of the immune system in damage and repair following ischemic and hemorrhagic insults to the brain. His focus is to identify the innate immune pathways involved in inducing secondary injury and driving repair in these disease processes. He aims to develop a seamless connection between bench research and clinical practice to improve basic understanding of the immune response to cerebrovascular injury that will translate to improved patient care.

He received his initial research training at Johns Hopkins University under Dr. Justin Hanes and Rangaramanujam Kannan. He focused on optimizing delivery of nanotherapeutics to the central nervous system. Specifically, he developed densely coated non-viral gene vectors able to rapidly traverse the extracellular space and effectively deliver their cargo to their target cell. In this way, he was able to construct therapeutic schemes for a glioblastoma rodent model using convection-enhanced delivery and for a Parkinson’s disease rodent model using systemic administration with focused ultrasound targeted blood brain barrier opening. This work was the basis of four patents as well as three R01 and one R24 NIH funded grants.

He subsequently developed interest in secondary injury related to cerebrovascular disease and received training in neuroimmunology from Dr. Dorian McGavern at the National Institutes of Health. He focused on the myeloid cell responses following hemorrhagic stroke and employed a combination of immunology techniques to describe the interplay between invading monocytes and microglia and their role in acute injury and repair. Using the tools developed for this project he also delineated the mechanism by which myelomonocytic cells initiate meningeal repair following traumatic brain injury and determined that the presence of a systemic infection distracts the myelomonocytic cells and interferes with the immune driven reparatory.

He joined the UTSouthwestern department of Neurosurgery and the O'Donnell Jr. Brain Institute and aims to characterize the immune drivers of secondary injury following aneurysmal subarachnoid hemorrhage, focusing on 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 as well as the role of intracranial pressure fluctuations in triggering the initial immune response.

• Development of therapeutics for intraarterial immunomodulation for chronic subdural hemorrhage
• Immune response to acute intracranial pressure fluctuations
• Innate immune drivers of secondary injury following aneurysmal subarachnoid hemorrhage

Featured Publications

Proteostasis Modulation in Germline Missense von Hippel Lindau Disease.

Chittiboina P, Mandal D, Bugarini A, Asuzu DT, Mullaney D, Mastorakos P, Stoica S, Alvarez R, Scott G, Maric D, Elkahloun A, Zhuang Z, Chew EY, Yang C, Linehan M, Lonser RR, Clin Cancer Res 2023 Jun 29 12 2199-2209

Glia limitans superficialis oxidation and breakdown promote cortical cell death after repetitive head injury.

Mason HD, Johnson AM, Mihelson NA, Mastorakos P, McGavern DB, JCI Insight 2021 Oct 6 19

Antimicrobial immunity impedes CNS vascular repair following brain injury.

Mastorakos P, Russo MV, Zhou T, Johnson K, McGavern DB, Nat Immunol 2021 Oct 22 10 1280-1293

Temporally distinct myeloid cell responses mediate damage and repair after cerebrovascular injury.

Mastorakos P, Mihelson N, Luby M, Burks SR, Johnson K, Hsia AW, Witko J, Frank JA, Latour L, McGavern DB, Nat Neurosci 2021 Feb 24 2 245-258

The anatomy and immunology of vasculature in the central nervous system.

Mastorakos P, McGavern D, Sci Immunol 2019 Jul 4 37

Biodegradable brain-penetrating DNA nanocomplexes and their use to treat malignant brain tumors.

Mastorakos P, Zhang C, Song E, Kim YE, Park HW, Berry S, Choi WK, Hanes J, Suk JS, J Control Release 2017 Sep 262 37-46

Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain.

Mastorakos P, Song E, Zhang C, Berry S, Park HW, Kim YE, Park JS, Lee S, Suk JS, Hanes J, Small 2016 Feb 12 5 678-85

Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy.

Mastorakos P, da Silva AL, Chisholm J, Song E, Choi WK, Boyle MP, Morales MM, Hanes J, Suk JS, Proc Natl Acad Sci U S A 2015 Jul 112 28 8720-5

Uniform brain tumor distribution and tumor associated macrophage targeting of systemically administered dendrimers.

Zhang F, Mastorakos P, Mishra MK, Mangraviti A, Hwang L, Zhou J, Hanes J, Brem H, Olivi A, Tyler B, Kannan RM, Biomaterials 2015 Jun 52 507-16

Highly PEGylated DNA Nanoparticles Provide Uniform and Widespread Gene Transfer in the Brain.

Mastorakos P, Zhang C, Berry S, Oh Y, Lee S, Eberhart CG, Woodworth GF, Suk JS, Hanes J, Adv Healthc Mater 2015 May 4 7 1023-33

 Featured Books

General Principles for the Management of Ruptured and Unruptured Intracranial Aneurysms. In Principles of Neurological Surgery

Mastorakos P. Ding D. Starke R. (2018). Elsevier

Treatment of the Adult Chiari I Malformation. In The Chiari Malformations

Mastorakos P. Heiss J. (2020). Springler

Pituitary Adenomas. In Textbook of Pediatric Neurosurgery

Taylor DG. Mastorakos P. Paisan GM. Pomeraniec IJ. Lopes MB. Jane JAJ. (2019). Springer Nature

Perioperative Challenges During Cerebrovascular Surgery. In Essentials of Neurosurgical Anesthesia and Critical Care

Mastorakos P. Raper DMS. Liu KC. (2020). Springer

Predicting Outcomes of Stereotactic Radiosurgery for Dural Arteriovenous Fistulas. In Cranial and spinal dural arteriovenous fistulas

Chandrabhatla AS. Mastorakos P. Chen CJ. Ding D. Sheehan J. (2022). Springer Nature

• Disease-Oriented Clinical Scholars (DOCS) program Award, UTSouthwestern
  (2023)
• Excellence in research award, Department of neurosurgery, University of Virginia
  (2022)
• Jane - Nugent basic science presentation award, The Neurosurgical Society of the Virginias
  (2022)
• Donald O. Quest, MD, FAANS(L) Basic Science Award, AANS Young Neurosurgeons Research Forum
  Immunology of Cerebrovascular Injury: Innate Drivers of Damage and Repair (2021)
• Jane - Nugent basic science presentation award, The Neurosurgical Society of the Virginias
  (2021)
• National Institute of Neurological Disorders and Stroke Clinical Research Excellence Award
  Intrathecal endoscopy for spinal arachnoiditis: lessons learned from a single center experience (2021)
• National Institute of Neurological Disorders and Stroke Directors Award
  For outstanding collaboration and leadership in efforts to understand the mechanism of edema formation following cerebrovascular injury (2021)
• National Institutes of Health Fellows Award for Research Excellence
  (2021)
• Jane - Nugent basic science presentation award, The Neurosurgical Society of the Virginias
  (2019)
• Immunology Interest Group award - Neuroimmunology session, National Institutes of Health
  (2018)
• Award for Research Excellence, Center for Nanomedicine/ Johns Hopkins University
  (2014)
• Empeirikeion Scholarship for support of research fellowship
  (2014)

• AANS/CNS Cerebrovascular section (2015)
• American Association of Neurological Surgeons (2015)
• Congress of Neurological Surgeons (2015)