Item Details

title

EFFECTS OF MICROGRAVITY AND MISSION-RELEVANT DOSES OF SPACE RADIATION ON THE HUMAN HEMATOPOIETIC SYSTEM

author

Kuhlman, Bradford M

abstract

Space exploration beyond low Earth orbit (LEO) exposes astronauts to unique environmental stressors, including microgravity and space radiation, which collectively pose significant risks to human health. In these studies, we sought to examine the combined effects of these factors on the human hematopoietic system, with a focus on immune dysfunction and cancer risk during long-duration space missions. Simulated microgravity was found to impair natural killer (NK) cell cytotoxic activity against leukemic cells, with continuous microgravity exposure exacerbating these effects. Radiation exposure, particularly from high-Linear Energy Transfer (LET) particles, resulted in pronounced splenomegaly in murine avatars which had been engrafted with human hematopoietic systems. Additionally, significant increases in the T-cell populations of these mice were observed across multiple tissues, suggesting the development of possible hematologic malignancy, such as leukemia. To mitigate these challenges, the dissertation explores pharmacological interventions targeting DNA repair pathways, antioxidant therapies, and advancements in spacecraft shielding and artificial gravity systems. The findings presented herein underscore the critical need for integrated countermeasures and molecular-level investigations to ensure the safety and success of deep-space exploration missions.

subject

Carcinogenesis

Hematopoiesis

Microgravity

Space Health

Space Radiation

contributor

Pardee, Timothy S (advisor)

Porada, Christopher D (committee member)

Almeida-Porada, Graca (committee member)

Soker, Shay (committee member)

Walker, Stephen J (committee member)

date

2025-06-24T08:36:05Z (accessioned)

2025 (issued)

degree

Physiology and Pharmacology (discipline)

embargo

2027-06-23 (terms)

2027-06-23 (liftdate)

identifier

http://hdl.handle.net/10339/110984 (uri)

language

en (iso)

publisher

Wake Forest University

type

Dissertation