Protein Phosphatases: Emerging Drug Targets for Heart Failure

Reduced PI3K(p110α) induces atrial myopathy, and PI3K-related lipids are dysregulated in athletes with atrial fibrillation

S Bass-Stringer, BC Bernardo, GS Yildiz, A Matsumoto, H Kiriazis, CA Harmawan, CMK Tai, R Chooi, L Bottrell, M Ezeani, DG Donner, AA D'Elia, JYY Ooi, NA Mellett, J Luo, EI Masterman, K Janssens, G Olshansky, EJ Howden, JH Cross

2025-12-01

Background: Elucidating mechanisms underlying atrial myopathy, which predisposes individuals to atrial fibrillation (AF), will be ..

Generation and evaluation of a novel PI3K-targeting gene therapy in the failing mouse heart and healthy sheep heart

S Bass-Stringer, DG Donner, CN May, A Matsumoto, EI Masterman, AA D'Elia, YC Chen, H Kiriazis, J Luo, R Chooi, CLC Ming, P Gregorevic, CJ Thomas, BC Bernardo, KL Weeks, JR McMullen

2025-09-01

Heart failure (HF) remains a clinical challenge with cardiac dysfunction typically progressing even with treatment, and heart tran..

Lipidomic Profiling of a Preclinical Model of Streptozotocin-Induced Diabetic Cardiomyopathy Reveals Potential Plasma Biomarkers

BC Bernardo, AN Faulkner, T Wang, K Huynh, PJ Meikle, KL Weeks, YK Tham

2025-07-01

New insights into diabetes-induced cardiac pathology

KL Weeks, BC Bernardo, JR Bell, LMD Delbridge, KM Mellor

2025-06-01

Individuals with diabetes have an elevated risk of heart disease, and there is a significant clinical need for evidence-based trea..

PP2A-B56α is a key determinant of cardiac protein phosphorylation and functional responses to β-adrenergic signalling

A Güran, Y Ji, P Fang, KT Pan, H Urlaub, M Avkiran, C Lenz, KL Weeks

2025-06-01

B56α is a protein phosphatase 2 A (PP2A) regulatory subunit which modulates the heart's inotropic response to acute β-adrenergic r..

Adeno-Associated Viruses as Gene Delivery Tools for Diabetic Heart Disease and Failure: Key Considerations for Clinicians and Preclinical Researchers

KL Weeks, BC Bernardo

2025-02-01

Diabetes is becoming more common worldwide, and people with diabetes are twice as likely to experience heart problems compared to ..

Sex-specific regulation of the cardiac transcriptome by the protein phosphatase 2A regulatory subunit B55α

NM Sergienko, AJ Trewin, H Kiriazis, AJA Raaijmakers, DG Donner, VC Garside, KA Smith, JR Bell, KM Mellor, LMD Delbridge, JR McMullen, KL Weeks

2024-12-01

Protein phosphatase 2A (PP2A) regulatory subunit B55α has been implicated in the transcriptional regulation of cardiac growth and ..

Male and female atria exhibit distinct acute electrophysiological responses to sex steroids

SP Wells, C O'Shea, S Hayes, KL Weeks, P Kirchhof, LMD Delbridge, D Pavlovic, JR Bell

2024-09-01

The electrophysiological properties of the hearts of women and men are different. These differences are at least partly mediated b..

Distinct functional and molecular profiles between physiological and pathological atrial enlargement offer potential new therapeutic opportunities for atrial fibrillation

YC Chen, S Wijekoon, A Matsumoto, J Luo, H Kiriazis, E Masterman, G Yildiz, J Cross, AC Parslow, R Chooi, J Sadoshima, DW Greening, KL Weeks, JR McMullen

2024-08-01

Atrial fibrillation (AF) remains challenging to prevent and treat. A key feature of AF is atrial enlargement. However, not all atr..

A gene therapy targeting medium-chain acyl-CoA dehydrogenase (MCAD) did not protect against diabetes-induced cardiac pathology

Kate L Weeks, Helen Kiriazis, Glenn D Wadley, Emma I Masterman, Nicola M Sergienko, Antonia JA Raaijmakers, Adam J Trewin, Claudia A Harmawan, Gunes S Yildiz, Yingying Liu, Brian G Drew, Paul Gregorevic, Lea MD Delbridge, Julie R McMullen, Bianca C Bernardo

2024-01-01

Diabetic cardiomyopathy describes heart disease in patients with diabetes who have no other cardiac conditions but have a higher r..

Regulation of mitochondrial calcium uniporter expression and calciumdependent cell signaling by lncRNA Tug1 in cardiomyocytes

AJ Trewin, KL Weeks, GD Wadley, S Lamon

2023-10-01

Cardiomyocyte calcium homeostasis is a tightly regulated process. The mitochondrial calcium uniporter (MCU) complex can buffer ele..

Cellular Mechanisms Mediating Exercise-Induced Protection against Cardiotoxic Anthracycline Cancer Therapy

S Dozic, EJ Howden, JR Bell, KM Mellor, LMD Delbridge, KL Weeks

2023-05-01

Anthracyclines such as doxorubicin are widely used chemotherapy drugs. A common side effect of anthracycline therapy is cardiotoxi..

Estrogen receptor alpha deficiency in cardiomyocytes reprograms the heart-derived extracellular vesicle proteome and induces obesity in female mice

YK Tham, BC Bernardo, B Claridge, GS Yildiz, LML Woon, S Bond, H Fang, JYY Ooi, A Matsumoto, J Luo, CMK Tai, CA Harmawan, H Kiriazis, DG Donner, NA Mellett, ED Abel, SA Khan, DP De Souza, SNE Doomun, K Liu

2023-03-01

Dysregulation of estrogen receptor alpha (ERα) has been linked with increased metabolic and cardiovascular disease risk. Here, we ..

HFpEF etiology – Can focus on sex-specific mechanisms deliver insights for all?

LMD Delbridge, JR Bell, KL Weeks, AJA Raaijmakers, KM Mellor

2022-12-01

Lymphangiogenesis: A new player in the heart's adaptive response to exercise

S Dozic, JV Janssens, KL Weeks

2022-07-01

Maternal obesity: influencing the heart right from the start

NM Sergienko, JR Bell, KL Weeks

2022-07-01

Protein phosphatase 2A in the healthy and failing heart: New insights and therapeutic opportunities

NM Sergienko, DG Donner, LMD Delbridge, JR McMullen, KL Weeks

2022-03-01

Protein phosphatases have emerged as critical regulators of phosphoprotein homeostasis in settings of health and disease. Protein ..

A protocol for rapid and parallel isolation of myocytes and non-myocytes from multiple mouse hearts

GE Farrugia, MA McLellan, KL Weeks, A Matsumoto, CD Cohen, C Krstevski, TL Gaynor, AC Parslow, JR McMullen, AR Pinto

2021-12-17

This protocol features parallel isolation of myocytes and non-myocytes from murine hearts. It was designed with considerations for..

A Step-By-Step Method to Detect Neutralizing Antibodies Against AAV using a Colorimetric Cell-Based Assay

S Bass-Stringer, CJ Thomas, CN May, P Gregorevic, KL Weeks, JR McMullen

2021-12-01

Recombinant adeno-associated viruses (rAAV) have proven to be a safe and successful vector for transferring genetic material to tr..

FoxO1 is required for physiological cardiac hypertrophy induced by exercise but not by constitutively active PI3K

KL Weeks, YK Tham, SG Yildiz, Y Alexander, DG Donner, H Kiriazis, CA Harmawan, A Hsu, BC Bernardo, A Matsumoto, RA DePinho, E Dale Abel, EA Woodcock, JR McMullen

2021-04-01

The insulin-like growth factor 1 receptor (IGF1R) and phosphoinositide 3-kinase p110a (PI3K) are critical regulators of exercise-i..