||1R01CA244271-01A1 Interpret this number
||University Of Iowa
||Sleep Disordered Breathing as a Targetable Risk Factor in Multiple Myeloma
Sleep apnea is a common and underdiagnosed syndrome that impacts at least 4% of American adults and
is associated with heart disease, stroke, diabetes, and cancer mortality. In patients with sleep apnea,
arterial oxygen saturation intermittently falls. Cyclic episodes are typically followed by rapid re-oxygenation.
This cycle occurs as often as 60 times per hour, resulting in chronic intermittent hypoxia (CIH), a dynamic
physiology that is distinct from static hypoxia. Our lab is pioneering the study of CIH’s effects on the bone
marrow, immunity, and the development of hematological malignancies and we now propose the critical
studies necessary to translate our work to human patients. We propose that CIH can cause resistance to
chemotherapy by increasing the abundance of tumor-associated macrophages (TAMs). In this proposal, we
aim: Aim 1: Test the hypothesis that severity of nighttime chronic intermittent hypoxia promotes TAMs
burden Aim 2: Test the hypothesis that continuous positive airway pressure (CPAP) treatment modulates
the abundance and gene expression of CD163+ CD206+ macrophages, and Aim 3: Test the hypothesis
that chronic intermittent hypoxia decreases the probability of complete remission in newly diagnosed
myeloma. By the end of the project period, we will have established that CIH has a clinically meaningful
impact on the bone marrow, we will have performed the first deep characterization of TAMs in the context of
CIH, and we will have determined the degree to which CIH severity is linked to poor response to
Challenges and inclusive practices for LGBTQIA2S+ scientists in the American Physiological Society.
, Bates M.L.
, Roepke T.A.
American journal of physiology. Heart and circulatory physiology, 2022-07-01; 323(1), p. H121-H124.