Prisco Lab

Sasha Prisco

The overarching goal of the Prisco Lab is to identify approaches to improve outcomes for patients with pulmonary hypertension. Specifically, our lab investigates the mechanisms of pulmonary vascular remodeling and right ventricular dysfunction, as right ventricular function is a strong predictor of survival for patients with pulmonary hypertension. We integrate studies in rodent models with findings from patients.

Sasha Z. Prisco, MD, PhD Faculty Bio

Current Lab Projects

Altering the Intestinal Microbiome to Improve Right Ventricular Function in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension is a progressive vasculopathy which increases right ventricular afterload, leading to right ventricular failure. Right ventricular function is the greatest predictor of survival in pulmonary arterial hypertension. Unfortunately, there are no current pharmacologic therapies that directly target the failing right ventricle. Our recent preclinical data demonstrated pathological inflammation through activation of the cytokine receptor glycoprotein 130 induced deleterious microtubule remodeling, downregulation of junctophilin-2 (an essential protein that maintains t-tubule structure and function), and depressed right ventricular function in pulmonary arterial hypertension. Emerging data show alterations in gut microbiota disrupt the intestinal barrier, which permits bacterial translocation, and subsequently activates systemic inflammation, suggesting that modulating the microbiome may be an approach to mitigate inflammation. We recently identified that modifying the gut microbiome with intermittent fasting improved right ventricular function and postulate that increased abundance of Lactobacillus underlies these benefits. We are testing the hypothesis that Lactobacillus supplementation combats pathological gut dysbiosis, which prevents immune cell activation, and subsequent glycoprotein 130-mediated microtubule remodeling. Additionally, we are exploring how modulating the microbiome/mycobiome composition affects pulmonary arterial hypertension and right ventricular function.

Investigating the Role of the Gut Microbiome in Pulmonary Hypertension Due to Lung Disease

Pulmonary hypertension secondary to chronic lung disease (WHO group 3 pulmonary hypertension) is the second most common cause of pulmonary hypertension. Patients with pulmonary hypertension due to chronic lung disease have a poor prognosis with median survival rates of 2-5 years. Right ventricular function is one of the greatest predictors of survival in pulmonary hypertension due to lung disease. In our translational research program, we integrate preclinical and clinical findings from WHO group 3 pulmonary hypertension patients to determine whether targeting the microbiome could be a novel therapeutic approach for pulmonary hypertension due to lung disease.

Publications

  1. Kazmirczak, F., Thenappan, T., Prins, K. W., & Prisco, S. Z. (2023). Sex Differences in Right Ventricular Function between Groups 1 and 3 Pulmonary Hypertension. Pulm Circ, 13(3), e12288. PMID: 37719340.
  2. Kazmirczak, F., Hartweck, L. M., Vogel, N. T., Mendelson, J. B., Park, A. K., Raveendran, R. M., O-Uchi, J., Jhun, B. S., Prisco, S. Z., & Prins, K. W. (2023). Intermittent Fasting Activates AMP-Kinase to Restructure Right Ventricular Lipid Metabolism and Microtubules. JACC Basic Transl Sci, 8(3), 239-254. PMID: 37034280.
  3. Moutsoglou, D. M., Tatah, J., Prisco, S. Z., Prins, K. W., Staley, C., Lopez, S., Blake, M., Teigen, L., Kazmirczak, F., Weir, E. K., Kabage, A. J., Guan, W., Khoruts, A., & Thenappan, T. (2023). Pulmonary Arterial Hypertension Patients Have a Proinflammatory Gut Microbiome and Altered Circulating Microbial Metabolites. Am J Respir Crit Care Med, 207(6), 740-756. PMID: 36343281.
  4. Prisco, S. Z., Kazmirczak, F., Thenappan, T., & Prins, K. W. (2022). Ingenuity pathway analysis of the human cardiac cell Atlas identifies differences between right and left ventricular cardiomyocytes. Pulm Circ, 12(1), e12011. PMID: 35506094.
  5. Prisco, S. Z., Hartweck, L., Keen, J. L., Vogel, N., Kazmirczak, F., Eklund, M., . . . Prins, K. W. (2022). Glyoxylase-1 combats dicarbonyl stress and right ventricular dysfunction in rodent pulmonary arterial hypertension. Front Cardiovasc Med, 9, 940932. PMID: 36093169.
  6. Prisco, S. Z., Eklund, M., Moutsoglou, D. M., Prisco, A. R., Khoruts, A., Weir, E. K., Thenappan, T., & Prins, K. W. (2021). Intermittent Fasting Enhances Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension. J Am Heart Assoc, 10(22), e022722. PMID: 34747187.
  7. Prisco, S. Z., Eklund, M., Raveendran, R., Thenappan, T., & Prins, K. W. (2021). With No Lysine Kinase 1 Promotes Metabolic Derangements and RV Dysfunction in Pulmonary Arterial Hypertension. JACC Basic Transl Sci, 6(11), 834-850. PMID: 34869947.
  8. Prisco, S. Z., Hartweck, L. M., Rose, L., Lima, P. D. A., Thenappan, T., Archer, S. L., & Prins, K. W. (2022). Inflammatory Glycoprotein 130 Signaling Links Changes in Microtubules and Junctophilin-2 to Altered Mitochondrial Metabolism and Right Ventricular Contractility. Circ Heart Fail, 15(1), e008574. PMID: 34923829.
  9. Keen, J., Prisco, S. Z., & Prins, K. W. (2021). Sex Differences in Right Ventricular Dysfunction: Insights From the Bench to Bedside. Frontiers in Physiology, 11(1800). PMID: 33536939.
  10. Prisco, S. Z., Rose, L., Potus, F., Tian, L., Wu, D., Hartweck, L., Al-Qazazi, R., Neuber-Hess, M., Eklund, M., Hsu, S., Thenappan, T., & Prins, K. W. (2020). Excess Protein O-GlcNAcylation Links Metabolic Derangements to Right Ventricular Dysfunction in Pulmonary Arterial Hypertension. Int J Mol Sci, 21(19). PMID: 33019763.
  11. Prisco, S. Z., Thenappan, T., & Prins, K. W. (2020). Treatment Targets for Right Ventricular Dysfunction in Pulmonary Arterial Hypertension. JACC Basic Transl Sci, 5(12), 1244-1260. PMID: 33426379.
Lab Members

photo of Prisco lab members in a group outside the lab building.
Sasha Prisco

Sasha Prisco, M.D., Ph.D.
Principal Investigator
I am a cardiovascular physician-scientist who specializes in treating pulmonary hypertension.
Interesting fact: My husband is also a cardiovascular physician-scientist and my sister is a physician-scientist in another field. I enjoy going on walks and bike rides with my family.

Ben Kremer

Benjamin Kremer, B.S.
Research Technician
Dual major in Genetics & Cell Development and Ecology, Evolution, and Behavior at the University of Minnesota – Twin Cities.
Graduated in 2023
Interesting fact: When I was little, I would wander my parent's farm "hunting" for skunks. To my dismay and my parent's delight, I never caught one.

Truc Ho

Truc Ho, B.S.
Volunteer
Major: Cellular and Organismal Physiology. Minor is Spanish Studies at the University of Minnesota – Twin Cities
Graduated in 2023
Interesting fact: I really enjoy baking!

Elizabeth Ngo

Elizabeth Ngo
Undergraduate Researcher
Major: Biomedical Engineering
Expected Graduation 2026
Interesting fact: I have a black belt in tae-kwon-do. In my free time, I like to read and play the piano.