Targeting the sarcomere to correct muscle function

PM Hwang, BD Sykes - Nature reviews Drug discovery, 2015 - nature.com
Various human diseases can disrupt the balance between muscle contraction and
relaxation. Sarcomeric modulators can be used to readjust this balance either indirectly by …

Heart failure with preserved ejection fraction: The pathophysiological mechanisms behind the clinical phenotypes and the therapeutic approach

L Stoicescu, D Crişan, C Morgovan, L Avram… - International Journal of …, 2024 - mdpi.com
Heart failure (HF) with preserved ejection fraction (HFpEF) is an increasingly frequent form
and is estimated to be the dominant form of HF. On the other hand, HFpEF is a syndrome …

Optogenetic control of cellular forces and mechanotransduction

L Valon, A Marín-Llauradó, T Wyatt, G Charras… - Nature …, 2017 - nature.com
Contractile forces are the end effectors of cell migration, division, morphogenesis, wound
healing and cancer invasion. Here we report optogenetic tools to upregulate and …

Drug specificity and affinity are encoded in the probability of cryptic pocket opening in myosin motor domains

A Meller, JM Lotthammer, LG Smith, B Novak, LA Lee… - Elife, 2023 - elifesciences.org
The design of compounds that can discriminate between closely related target proteins
remains a central challenge in drug discovery. Specific therapeutics targeting the highly …

Myosin-II-mediated cell shape changes and cell intercalation contribute to primitive streak formation

E Rozbicki, M Chuai, AI Karjalainen, F Song… - Nature cell …, 2015 - nature.com
Primitive streak formation in the chick embryo involves large-scale highly coordinated flows
of more than 100,000 cells in the epiblast. These large-scale tissue flows and deformations …

Effects of Aficamten on cardiac contractility in a feline translational model of hypertrophic cardiomyopathy

AN Sharpe, MS Oldach, VN Rivas, JL Kaplan… - Scientific Reports, 2023 - nature.com
Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease in
humans and cats and lacks efficacious pharmacologic interventions in the preclinical phase …

Non‐muscle myosins in tumor progression, cancer cell invasion, and metastasis

JL Ouderkirk, M Krendel - Cytoskeleton, 2014 - Wiley Online Library
The actin cytoskeleton, which regulates cell polarity, adhesion, and migration, can influence
cancer progression, including initial acquisition of malignant properties by normal cells …

[HTML][HTML] Specific myosins control actin organization, cell morphology, and migration in prostate cancer cells

KA Makowska, RE Hughes, KJ White, CM Wells… - Cell reports, 2015 - cell.com
We investigated the myosin expression profile in prostate cancer cell lines and found that
Myo1b, Myo9b, Myo10, and Myo18a were expressed at higher levels in cells with high …

An apical MRCK-driven morphogenetic pathway controls epithelial polarity

C Zihni, E Vlassaks, S Terry, J Carlton, TKC Leung… - Nature cell …, 2017 - nature.com
Polarized epithelia develop distinct cell surface domains, with the apical membrane
acquiring characteristic morphological features such as microvilli. Cell polarization is driven …

The future of heart failure with preserved ejection fraction: Deep phenoty** for targeted therapeutics

FR Heinzel, SJ Shah - Herz, 2022 - Springer
Heart failure (HF) with preserved ejection fraction (HFpEF) is a multi-organ, systemic
syndrome that involves multiple cardiac and extracardiac pathophysiologic abnormalities …