Peripartum cardiomyopathy (PPCM) is a life-threatening, idiopathic systolic dysfunction that manifests late in pregnancy or up to one year postpartum. While clinical risk factors like advanced maternal age, lactation, pre-eclampsia, and increased parity are well-documented , the field currently suffers from a lack of mechanistic clarity and a reliance on imperfect preclinical models that replicate the final disease phenotype without capturing its root causes. Our future research aims to fundamentally change how PPCM is modeled and understood.
- Delineating the Risk-Factor Driven Transition to Failure: Before introducing artificial pathological stress, this project will systematically evaluate how known clinical risk factors (such as high parity or the heavy metabolic demands of lactation) perturb normal cardiovascular feedback loops. We will identify the tipping points where normal physiological adaptations cross over into maladaptive, irreversible remodeling.
- Mapping Energetic Collapse and Positive Feedback Loops: Using an integrative physiology framework, we will study how chronic or repeated homeostatic disruptions trigger detrimental positive feedback loops. This project will investigate whether PPCM is driven by systemic and cardiovascular energetic collapse, rendering the maternal heart incapable of managing the high circulatory demands of sustaining two lives.
- Developing High-Fidelity Etiological Models: The ultimate goal of this research arm is to generate novel murine models that realistically replicate the underlying cellular, molecular, and organ-system features driving PPCM pathology. By pinpointing these exact metabolic switches and regulatory nodes, we expect to discover novel mechanistic targets that can yield fresh therapeutic options for a patient population with highly limited clinical interventions.