Paras Kumar Mishra, PhD
Associate Professor at University of Nebraska Medical Center
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Paras Kumar Mishra, PhD
Associate Professor at University of Nebraska Medical Center
Welcome to the Mishra Lab
Innovating Research in Diabetes-Induced Heart Failure
Diabetes affects over 422 million people worldwide, significantly increasing the risk of heart failure—a condition where the heart cannot pump efficiently to meet the body's needs. Alarmingly, diabetes doubles the likelihood of heart failure, underscoring an urgent need for targeted research and therapies. The Mishra Lab, led by Paras Kumar Mishra, PhD, is dedicated to unraveling the unique mechanisms of diabetes-induced heart failure and developing innovative treatments to improve patient outcomes.
Diabetes affects over 422 million people worldwide, significantly increasing the risk of heart failure—a condition where the heart cannot pump efficiently to meet the body's needs. Alarmingly, diabetes doubles the likelihood of heart failure, underscoring an urgent need for targeted research and therapies. The Mishra Lab, led by Paras Kumar Mishra, PhD, is dedicated to unraveling the unique mechanisms of diabetes-induced heart failure and developing innovative treatments to improve patient outcomes.
Myocardial Cell Death: The Precursor to Heart Failure
Myocardial cell death is a critical precursor to heart failure. In diabetic patients, increased myocardial lipotoxicity and mitochondrial dysfunction trigger cell death pathways that compromise heart function. Our research has revealed that diabetic cardiomyopathy, characterized by unique molecular features, affects women disproportionately, emphasizing the need for targeted and inclusive therapeutic approaches.
To address this, the Mishra Lab has established comprehensive guidelines for evaluating cell death, offering a standardized framework for researchers worldwide. By understanding and mitigating myocardial cell death, we aim to slow or prevent the progression of heart failure in diabetic patients.
Myocardial cell death is a critical precursor to heart failure. In diabetic patients, increased myocardial lipotoxicity and mitochondrial dysfunction trigger cell death pathways that compromise heart function. Our research has revealed that diabetic cardiomyopathy, characterized by unique molecular features, affects women disproportionately, emphasizing the need for targeted and inclusive therapeutic approaches.
To address this, the Mishra Lab has established comprehensive guidelines for evaluating cell death, offering a standardized framework for researchers worldwide. By understanding and mitigating myocardial cell death, we aim to slow or prevent the progression of heart failure in diabetic patients.
Pioneering Discoveries in Ferroptosis and Heart Disease
The Mishra Lab has made significant strides in identifying the molecular drivers of heart failure in diabetic patients, with a focus on ferroptosis, a regulated form of cell death.
The Mishra Lab has made significant strides in identifying the molecular drivers of heart failure in diabetic patients, with a focus on ferroptosis, a regulated form of cell death.
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Myocardial Cell Death via Ferroptosis in Human Heart Failure
This landmark study established ferroptosis as a key driver of myocardial cell death in human heart failure, highlighting new therapeutic targets to preserve cardiac function. -
MMP9 Signaling and Ferroptosis
Building on this discovery, the lab uncovered the role of Matrix Metalloproteinase-9 (MMP9) in ferroptosis, providing critical insights into the signaling pathways that exacerbate heart failure.
Decoding the Unique Challenges of Diabetes-Induced Heart Failure
Diabetes-induced heart failure is distinct from non-diabetic heart failure due to its unique pathophysiology:
Diabetes-induced heart failure is distinct from non-diabetic heart failure due to its unique pathophysiology:
- Metabolic Remodeling: Diabetic hearts exhibit a shift from glucose to fatty acid metabolism, which increases mitochondrial stress and reduces energy efficiency.
- Mitochondrial Dysfunction: Impaired mitophagy leads to the accumulation of damaged mitochondria, exacerbating oxidative stress and triggering cell death.
- Sex-Specific Risks: Women face disproportionately higher risks of diabetic cardiomyopathy, necessitating research into gender-specific mechanisms.
Innovative Therapeutic Strategies
Our lab is exploring novel therapies to mitigate these challenges, including:
Our lab is exploring novel therapies to mitigate these challenges, including:
- miRNA Mimics: Regulating key pathways involved in metabolic remodeling and cell death.
- Hydrogen Sulfide Donors: Protecting mitochondrial integrity and reducing oxidative stress.
- MMP9 Inhibitors: Targeting matrix remodeling to prevent ferroptosis and improve heart function.
Join Us in Transforming Cardiac Care
The Mishra Lab is committed to advancing the understanding of diabetic heart failure, training the next generation of scientists, and translating research into impactful therapies. Whether you're a researcher, student, or collaborator, we invite you to connect with us and contribute to the fight against heart failure.
The Mishra Lab is committed to advancing the understanding of diabetic heart failure, training the next generation of scientists, and translating research into impactful therapies. Whether you're a researcher, student, or collaborator, we invite you to connect with us and contribute to the fight against heart failure.
Together, we can make a difference.
Mentoring is a cornerstone of my academic mission. My graduate students have achieved significant recognition, securing several prestigious national awards. Notably, one student won 1st place in The Science Coalition’s Fund It Forward Student Video Challenge in 2019 (Video Link) , while another garnered 2nd place at Research!America’s 2020 Flash Talks Competition during the National Health Research Forum (Link: https://www.unmc.edu/news.cfm?match=26235). Additionally, my students have been awarded the NIH F31, AHA Predoctoral, AHA Postdoctoral, and UNMC Presidential Graduate Fellowships and the UNMC Program of Excellence Assistantship, underscoring the high caliber of our research training and mentorship.