09/22/2026
By Marley O'Neil

The Francis College of Engineering, Department of Biomedical Engineering, invites you to attend a doctoral dissertation defense by Neal Lojek titled “A 3D hiPSC cortical tissue model for quantifying the effects of ionizing radiation on functional cortical networks.”

  • Date: Friday, Oct. 2, 2026
  • Time: 10 a.m. – noon
  • Location: Southwick 240

Committee

  • Advisor: Chiara E. Ghezzi, Associate Professor, Biomedical Engineering, University of Massachusetts Lowell
  • Bryan J. Black, Ph.D., Associate Principal Scientist, Cyprotex US
  • Yanfen Li, Assistant Professor, Biomedical Engineering, University of Massachusetts Lowell
  • Andrew M. Rogers, Associate Professor, Physics, University of Massachusetts Lowell
  • Erno Sajo, Professor, Medical Physics, University of Massachusetts Lowell

Brief Abstract

Ionizing radiation-induced brain injuries represent a rare but important type of neurological injury that remains poorly characterized due to a lack of reliable experimental models. Radiological injury to the central nervous system results from one of three injury types: radiotherapy to treat brain tumors, nuclear accidents or attacks, and potentially chronic exposure to space radiation on crewed NASA spaceflight missions beyond low Earth orbit. While these exposures differ in radiation quality, dose and dose rate, they share a conserved injury mechanism: radiation-induced ionizations generate reactive oxygen species, leading to DNA damage and other cellular and tissue-level injuries that, through mechanisms not yet fully understood, contribute to neurological dysfunction.

Historically, animal models have provided scientific insight into brain injuries due to ionizing radiation exposure; however, these are constrained by a lack of physiological relevance to humans and limited accessibility of cell- and tissue-level injury readouts. In vitro models have also been used; however, most rely on simplistic tissue culture platforms with limited relevance to human physiology and primarily assess injury using reductionist endpoints, such as DNA damage and clonogenic survival, that do not capture higher-order neurological function. Importantly, this limitation has created a critical knowledge gap regarding the cellular and tissue-level mechanisms by which ionizing radiation induces neuronal dysfunction, hindering efforts to assess and mitigate risks to human health.

The aim of this doctoral research thesis was to develop and validate an engineered three-dimensional in vitro model designed to investigate the effects of ionizing radiation on aspects of cerebral cortex tissue physiology and screen potential pharmacological preventions and countermeasures (NASA 2020 technological roadmap 6.5.2.2 & 6.5.2.3). The objective was to replicate essential physiological properties of human cortical tissue, including the neuroglial unit and mechanical properties, using an engineered dense hydrogel scaffold made of type I collagen, with integrated basement membrane proteins relevant to the native extracellular matrix and seeded with human or mouse neurons and glia.

Initial work benchmarked mechanical properties and cellular differentiation. The model was purpose-built to accommodate imaging of classic DNA damage markers and emerging functional readouts of neuroimmune injury. Additionally, first-of-its-kind electrophysiology recordings of 2D co-cultures were made using microelectrode arrays to measure the effects of ionizing radiation on neural network activity. Subsequently, this work utilized radiotherapy-relevant doses of ionizing proton radiation, computational energy transfer modeling and developed quantification methods for neuroimmune phenotypes. Finally, acute (1-hour) and chronic (7-day) doses of gamma radiation, relevant to crewed missions beyond low Earth orbit, allowed for a comparison of neuroimmune and electrophysiological phenotypes to understand the effects of dose rate on injury with and without radioprotective drug treatment.

In conclusion, this work established and applied a physiologically relevant human cortical tissue model to investigate radiation-induced neurobiological injury under both acute and chronic exposure conditions. Leveraging this platform, we characterized the effects of radiation and radioprotective intervention on cortical tissue function through complementary cellular injury endpoints and longitudinal electrophysiological assessments, capabilities not previously demonstrated in a single human tissue model. Collectively, this work introduces a novel experimental framework for studying radiation-induced neurological injury, provides important new insights into radiation neurobiology, and creates new opportunities for translational research in both radiotherapy-associated injury to normal tissue and human space health.