Welcome to the Collins Laboratory

Historically, females have been understudied in the context of preclinical and clinical trials, contributing to an overall reduced knowledge of basic female cardiovascular biology and also how the female heart responds to physiological and pathological stress. Therefore, the overall mission of the Collins lab is to understand the mechanisms contributing to female cardiovascular health and resilience.

Our Research and Contributions to Science

In the Collins Lab, we take a fully integrative physiology approach to examine how cellular, metabolic, and structural changes govern heart function in both health and disease. Our work spans multiple disciplines—including cardiac metabolism, chronobiology, and systemic physiology—to pioneer personalized approaches to cardiovascular medicine.

1. The Physiology of Pregnancy and the Postpartum Period

Pregnancy acts as a natural "stress test," challenging normal physiological homeostasis and forcing the maternal cardiovascular system to dynamically adapt. To meet the demands of maintaining both maternal and fetal circulation, negative feedback loops manage massive increases in blood volume and cardiac output.

Structural Remodeling: We have demonstrated that the heart adapts to increased preload by developing an adaptive, physiological hypertrophy that preserves cardiac output. This structural growth peaks at one-week postpartum. Notably, while pregnancy exhibits eccentric remodeling, the early postpartum period is uniquely characterized by concentric remodeling and increased cardiomyocyte cross-sectional area.

The Impact of Lactation: Our research demonstrates that lactation further modulates maternal cardiac adaptations. The energetically demanding process of lactation alters both the structural and metabolic remodeling of the maternal heart, regulating glucose incorporation into ancillary pathways.

The Gestational Metabolic Atlas: We documented a comprehensive metabolomic, proteomic, and transcriptomic atlas of the maternal heart, demonstrating that the heart undergoes sophisticated metabolic reprogramming and dynamic mitochondrial adjustments to sustain the hemodynamic demands of pregnancy. 

Unifying the Field: To improve reproducibility in maternal health research, we have led major consensus guidelines for assessing maternal cardiovascular physiology in vivo.

2. Cardiac metabolism and Organ Crosstalk

Periods of heightened cardiac output are energetically demanding, requiring a precise metabolic shift to sustain cardiac growth and function. We utilize cutting-edge methodologies—including high-resolution respirometry, bulk metabolomics, and stable isotope resolved metabolomics (13C glucose tracing)—to map these metabolic signatures.

The Glucose-Ketone Switch: During late pregnancy, the maternal heart experiences a reduction in glucose catabolism (characterized by increased Pdk4 expression), allowing glucose to be spared for ancillary anabolic pathways (amino acid, nucleotide, and phospholipid metabolism) to provide the building blocks for cardiac growth.

Liver-Heart Axis: To meet its energetic needs during this glucose shift, the heart relies on liver-derived ketone bodies acting through increased cardiac expression of the enzyme Bdh1. Our current NIH R01-funded work focuses on this critical node of organ-organ crosstalk, demonstrating that a lack of cardiomyocyte Bdh1 impairs normal maternal homeostatic adaptations.

3. Circadian Dysregulation and Environmental Stressors

A growing interest in the laboratory involves determining how modern lifestyle stressors perturb cardiac homeostatic processes. Because our transcriptional findings reveal distinct signatures of circadian dysregulation during normal pregnancy, we are actively expanding our program to examine the impact of sleep deprivation and shift work on maternal physiological adaptations and long-term cardiometabolic health.

4. Pregnancy-associated Cardiovascular Disease and Adverse Pregnancy Outcomes

We are investigating how extrinsic factors (diet, age, physical activity) and clinical conditions (obesity, diabetes, hypertension) disrupt homeostasis. We are particularly focused on identifying the regulatory failures driving pre-eclampsia (characterized by a shift toward concentric hypertrophy, high systemic resistance, and low volume) and peripartum cardiomyopathy (PPCM

5. Sex Disparities in Cardiac Resilience

We seek to understand why elderly women experience significantly higher rates of Heart Failure with Preserved Ejection Fraction (HFpEF) compared to men, and conversely, why females display greater cardiac resilience and distinct remodeling patterns following ischemic injuries, such as myocardial infarction.