Biology subjects

Holmes, K.

Publications and source records attributed to Holmes, K..

3 recordsLinked to original sources

bioRxiv2025

The menstrual cycle through the lens of a wearable device: insights into physiology, sleep, and cycle variability

Women on average have 450 menstrual cycles in a lifetime, but we lack a characterization of physiological biometrics across the cycle and lifespan. We analyzed 1.2 million days of data from 2,596 women who logged 42,759 menstrual cycles and wore a device that collected sleep and biometric data including resting heart rate (RHR), heart rate variability, respiratory rate, skin temperature, and blood oxygen saturation level. We generated novel quantifications of daily biometrics across ages and cycle lengths, finding that cycle length is strongly associated with how much cardiorespiratory metrics vary across the cycle. We observed greater cycle variability for participants who slept 6 versus 8 hours. A within-participant natural experiment showed that decreased sleep resulted in biometric changes regardless of cycle phase (e.g., RHR increased 1.2% with a 10% decrease in weekly sleep duration). These results lay a foundation to better understand and optimize female health and performance.

physiology↗

bioRxiv2024

Select autosomal dominant DFNA11 deafness mutations activate Myo7A in epithelial cells

Myosin-7A (Myo7A) is a motor protein crucial for the organization and function of stereocilia, specialized actin-rich protrusions on the surface of inner ear hair cells that mediate hearing. Mutations in Myo7A cause several forms of genetic hearing loss, including autosomal dominant DFNA11 deafness. Despite its importance, the structural elements of Myo7A that control its motor activity within cells are not well understood. In this study, we used cultured kidney epithelial cells to screen for mutations that activate the motor-dependent targeting of Myo7A to the tips of apical microvilli on these cells. Our findings reveal that Myo7A is regulated by specific IQ motifs within its lever arm, and that this regulation can function at least partially independent of its tail sequence. Importantly, we demonstrate that many of the DFNA11 deafness mutations reported in patients activate Myo7A targeting, providing a potential explanation for the autosomal dominant genetics of this form of deafness.

cell biology↗

bioRxiv2020

Mapping the unique and shared functions of oncogenic KRAS and RIT1 with proteome and transcriptome profiling

Aberrant activation of RAS oncogenes is prevalent in lung adenocarcinoma, with somatic mutation of KRAS occurring in [~]30% of tumors. Recently, we identified somatic mutation of the RAS-family GTPase RIT1 in lung adenocarcinoma, but relatively little is known about the biological pathways regulated by RIT1 and how these relate to the oncogenic KRAS network. Here we present quantitative proteomic and transcriptomic profiles from KRAS-mutant and RIT1-mutant isogenic lung epithelial cells and globally characterize the signaling networks regulated by each oncogene. We find that both mutant KRAS and mutant RIT1 promote S6 kinase, AKT, and RAF/MEK signaling, and promote epithelial-to-mesenchymal transition and immune evasion via HLA protein loss. However, KRAS and RIT1 diverge in regulation of phosphorylation sites on EGFR, USO1, and AHNAK proteins. The majority of the proteome changes are related to altered transcriptional regulation, but a small subset of proteins are differentially regulated by both oncoproteins at the post-transcriptional level, including intermediate filament proteins, metallothioneins, and MHC Class I proteins. These data provide the first global, unbiased characterization of oncogenic RIT1 network and identify the shared and divergent functions of oncogenic RIT1 and KRAS GTPases in lung cancer.

cancer biology↗