Mentorship in the Endocrinology of Sleep - The overarching goal of this application for a K24 Midcareer Investigator Award in Patient-Oriented Research
is to foster training of promising junior investigators in cutting edge patient-oriented research related to how
sleep biology influences cardiometabolic health. It capitalizes on the established network and resources of the
recently renewed UCLA CTSI that includes a highly successful KL2 program. Dr. Liu led a competitively-
funded Endocrine and Cardiometabolic Program in Sleep Biology at the University of Sydney, and since 2012,
he has led a similar interdisciplinary research program in Los Angeles supported by a 5 year NHLBI R01
“Hormonal mechanisms of sleep restriction” that is currently in its 3rd year. During his 10 years of mentoring,
he has trained 16 individuals: 10 remaining in academic medicine and 2 others in industry-related patient
orientated research. Three of his trainees won major US young investigator awards under his supervision. He
continues to support, mentor, and publish with former trainees, often long after they left his laboratory.
Disturbed sleep causes insulin resistance, promotes poor food choices, and curtails fat loss while dieting,
thereby reducing the effectiveness of standard weight loss programs. However, the cardiometabolic
consequences of disturbed sleep are not well recognized by the community, and the evidential bases to justify
widespread changes to community sleeping patterns for cardiometabolic health reasons are evolving. Showing
the mechanisms by which sleep restriction leads to cardiometabolic ill-health, particularly in older adults
according to sex, are critical steps in providing these data. Dr. Liu's goal is to mentor the next cadre of
independent clinical scientists focused on placing sleep alongside diet and exercise as part of healthy lifestyle,
by understanding hormonal mechanisms and consequences of disrupted, inadequate or misaligned sleep.
The work proposed in this application fulfill these goals. Aim 1 will reveal the hypothalmo-pituitary-adrenal
and hypothalamo-pituitary-gonadal mechanisms that cause testosterone-cortisol imbalance when sleep is
restricted in older men and women (20 in each group). In doing so, trainees will learn endocrine physiology and
chronobiological study design, IRB processes, recruitment skills, and hands-on study management. Aim 2 will
identify sex differences in these mechanisms, trainees will learn statistical methods and abstract/presentation/
manuscript preparation. Aim 3 requires trainees to discover new mechanisms by which sleep restriction causes
insulin resistance and alters appetite or food intake. Certain inflammatory mediators, hormones, or factors
related to ethnicity or age could be studied. Aim 3 fulfils broader expectations for trainees to have a second
project that is faster to accomplish, more exploratory, and driven by their interests and available resources, to
develop a line of research that complements and is separate from that of the mentors. Taken together, these
experiments will generate new knowledge of the relationship between sleep and hormonal cardiometabolic and
reproductive health, provide wide-ranging training opportunities, and generate future R and K proposals.