10/30/2026
By Ruiying Cheng

The Zuckerberg College of Health Sciences, Department of Biomedical and Nutritional Sciences, invites you to attend a Ph.D. dissertation defense by Ruiying Cheng titled “Pharmacological Modulation of Brain Iron Dysregulation.”

Event details

  • Candidate name: Ruiying Cheng
  • Date: Monday, Nov. 16, 2026
  • Time: 10 a.m. – Noon
  • Location: TBD
  • Dissertation title: Pharmacological Modulation of Brain Iron Dysregulation

Committee

  • Advisor: Jonghan Kim, Ph.D., Department of Biomedical and Nutritional Sciences, UMass Lowell
  • Dhimiter Bello, Ph.D., Department of Biomedical and Nutritional Sciences, UMass Lowell
  • Soumita Das, Ph.D., Department of Biomedical and Nutritional Sciences, UMass Lowell
  • Yuho Kim, Ph.D., Department of Physical Therapy and Kinesiology, UMass Lowell
  • Swati Betharia, Ph.D., Department of Pharmaceutical Sciences, Massachusetts College of Pharmacy and Health Sciences

Abstract

Brain iron is tightly regulated because it is essential for normal cellular and neurological function, while excessive or dysregulated iron can contribute to oxidative stress, mitochondrial dysfunction and neurodegeneration. Therapeutic modulation of pathological brain iron is challenging because effective chelation must be able to penetrate the blood-brain barrier (BBB) and reduce pathological iron without disrupting physiological iron homeostasis or causing systemic toxicity. This dissertation examined this problem from two complementary perspectives: chelator selection and drug delivery.

The first part of this dissertation reviewed the biological basis of brain and mitochondrial iron dysregulation in the context of neurodegenerative disease. An alternative iron chelator, N,N’-bis(2-mercaptoethyl)isophthalamide (NBMI), was then evaluated in cellular and animal models of iron overload. NBMI showed moderate ferrous iron binding affinity, reduced iron-associated cellular toxicity, labile iron, and oxidative stress in SH-SY5Y cells, and decreased systemic brain iron burden and oxidative stress in H67D mice. However, the reduction of brain iron did not show statistical significance, highlighting the limitations of systemic chelation for brain iron modulation.

The second part of this dissertation examined intranasal administration as an alternative strategy for CNS drug delivery. Current evidence for intranasal iron chelation was reviewed, followed by experimental evaluation of intranasally administered deferiprone (DFP). Intranasal DFP produced rapid brain exposure and a tissue distribution profile distinct from oral administration, with particularly high distribution in the olfactory bulbs. Repeated intranasal treatment produced behavioral effects without the hematological changes observed following high-dose oral treatment under the conditions examined, although substantial changes in total brain iron were still not detected.

Collectively, these findings indicate that effective CNS modulation depends not only on the iron-binding properties of the chelator itself, but also on pharmacokinetics, route of administration, tissue distribution, and the specific iron pool being targeted. The work summarized in this dissertation advances the field by integrating chelator properties with drug delivery considerations and by providing evidence that intranasal administration can alter CNS and peripheral exposure of an established iron chelator. These findings support an alternative strategy for developing CNS iron-modulating therapies aimed at improving therapeutic efficacy while minimizing systemic toxicity, with the potential to be applied to broader fields such as neurodegeneration studies and clinical research.

Keywords: brain iron dysregulation; iron chelation; intranasal drug delivery; pharmacokinetics; neurodegeneration.