This is an application for a K02 Independent Scientist Award. The candidate is a physician-scientist whose work to date has focused on sleep, circadian rhythms, hormones and their interactions as well as mathematical analyses and modeling of these physiologic functions. The associated funded R01 award """"""""Impact of Sleep Disruption on Menstrual Cycle Dynamics"""""""" is one example of her work and her interests. In that research project, she is investigating the physiologic basis behind the increased menstrual cycle abnormalities, decreased fertility and early miscarriage associated with rotating shift-work and night-work schedules. One of every fourteen working women works a variable schedule that includes both day and night shifts. The project investigates the effects of sleep disruption at specific phases of the menstrual cycle in the dynamics of pulsatile LH secretion; FSH, estrogen and progesterone levels; follicular and luteal phase length, and follicle growth. Cycle dynamics are being determined by daily menstrual logs, daily basal body temperature, daily urine and blood gonadotropin and steroid levels, month urine ovulation kits, and monthly pelvic ultrasonography during a four-month protocol, in addition to sleep recordings, sleep disruption and frequent blood sampling for sleep-LH relationships during a four-day inpatient stay during the third month of the protocol. During the term of this award, Dr. Klerman would continue the work described in the funded R01 and, with the resources available from the K02 award, develop her mathematical, statistical and bioinformatics skills with the expectation of applying these skills to the data collected in the R01 as well as to other sleep, circadian and endocrine data. The candidate's long-term objectives are to continue within academic medicine, conducting both basic clinical research in humans and the analyses of the interrelated and complex biological data sets of sleep, circadian rhythms and endocrinologic data.
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