Cardiovascular T32 Training Program

Education/Credentials
MD, Medicine, Medical College of Wisconsin
PhD, Physiology, Medical College of Wiconsin

Trainee 2019-2022

Mentor: Kurt Prins, MD, PhD

Research Project Area/Focus:
Investigating the Role of the Intestinal Micro- and Mycobiome in Pulmonary Hypertension

Accomplishments:
Clinical and Translational Science Institute (CTSI) Translational Research Development Program Grant (2020-22)
Physician-Scientist Training Program (PSTP) Academic Investment in Education Grant (received each year over four consecutive years) (2019-23)
Cardiovascular Retreat (Cardio Palooza) Best Fellow Poster Award (2019)
Northwestern Cardiovascular Young Investigators’ Forum Winner in Fellows Basic Science (2020)
National Institutes of Health Ruth L. Kirschstein Institutional National Research Service Award (T32 Grant) (2019-21)
Northwestern Cardiovascular Young Investigators’ Forum Finalist in Fellows Basic Science (2019)

Dr. Prisco on PubMed

Trainee 2019-2021

Mentor: Paul Iaizzo, PhD

Research Project Area/Focus:
Dr. Prisco was a cardiovascular diseases fellow and engineer with a strong interest in using mathematical modeling to better understand cardiovascular disease, develop better treatments, and improve patient care. Currently, he has two main research foci: computational fluid dynamics and artificial intelligence. He uses computational fluid dynamics to model complex blood flow in heart valves and cardiopulmonary bypass machines. Additionally, he is developing mathematical techniques to predict if valves placed percutaneously will leak following implantation. In cardiopulmonary bypass, he is working on better understanding how patients with multisystem organ failure maintain end-organ oxygenation while on bypass. Finally, he is currently using convolutional neural networks, a type of artificial intelligence, to diagnose subclinical cardiovascular disease in high-risk patients.

Accomplishments:
University of Minnesota: Anthony Garofalo Prevention Fellowship Award 2021

Dr. Prisco on PubMed

Education/Credentials
PhD, Experimental Pathology, Biomedical Sciences Graduate Program, University of Virginia

Trainee 2020-2022

Mentor: Bryce Binstadt, MD, PhD

Research Project Area/Focus:
Dr. Osinski's research involved two projects focused on improving the understanding of the role that stromal and vascular cells play in response to chronic inflammation in the mitral valves. These studies examined specific cellular processes and signaling molecules that are believed to be relevant to the mechanisms driving pathologies observed in rheumatic heart disease and other forms of endocarditis. To study this, she employed the use of the transgenic mouse model of arthritis K/B.g7 in which the mouse generates autoantibodies that prompt inflammation and fibrosis in the joints as well as the heart. Project 1 specifically focused on characterizing the lymphatics in the mitral valves of these mice and determining whether they promote or inhibit disease progression early on and later in valve inflammation. Her specific hypothesis was that lymphangiogenesis inhibits disease early on, but later promotes it. This project was motivated by data identifying new vascular structures in inflamed valves of K/B.g7 mice using cre-lox recombination lineage-tracing driven by the endothelial-specific Cdh5 promoter. These identified vessels express lymphatic markers VEGFR3 and LYVE1. Project 2 aimed to understand whether expression of IL4Rɑ in fibroblasts promotes valve inflammation and fibrosis. Previous work from the laboratory demonstrated that macrophage-produced IL-13 drives valve inflammation, but it remains unclear which cell types bind and respond to this cytokine to induce this pathology. She hypothesized that loss of IL4Rɑ in fibroblasts would protect against IL-13-driven valve inflammation and fibrosis. Both projects employed the use of cell-specific gene knockout murine lines, flow cytometry and histology assays, and human mitral valve samples to validate the presence of important cell types and proteins in patients with rheumatic disease and other inflammatory heart diseases. Since the mitral valve samples are obtained from deidentified, discarded tissue, this is not considered human research.

Dr. Osinski on PubMed

Education/Credentials
MD, University of Colorado Anschutz Medical Campus
PhD, Immunology, University of Colorado Anschutz Medical Campus

Trainee 2020-2023

Mentor: Thenappan Thenappan, MD

Research Project Area/Focus:
Daphne Moutsoglou, MD, PhD is a gastroenterology fellow at the University of Minnesota. She completed her PhD in immunology and MD in the combined Medical Scientist Training Program at the University of Colorado. At this time, her goals are to continue to conduct research in academia studying the interaction between the microbiome and immune system in disease. Under the Cardiology T32 training grant, she studied the role of the microbiome in pulmonary arterial hypertension (PAH) as well as the role of microbiota transplant therapy (previously known as fecal microbiota transplant) in two clinical trials, one in PAH and ulcerative colitis.
She has conducted a separate descriptive study of human microbiota in PAH and has found that the fecal microbiomes of PAH patients are different from healthy and family controls (those that cohabitate with patients with PAH). She has also found differences in gut microbial metabolites using targeted metabolomics. These data have been published.
Additionally, she has taken these findings and applied to the FDA, for an investigational new drug (IND) application (IRB# STUDY00012951, CT.gov#: NCT 04884971). During her time on this project, she has written the investigational new drug application to the FDA, submitted it, and communicated with the FDA regarding revisions to get its final approval. She has also completed the clinical trial and is currently analyzing the results.
To complete this analysis, she collected stool samples from trial patients and is testing for engraftment of fecal microbiota. She is also analyzing blood from patients in the trial to look for markers of disease and changes in microbial metabolites.
She also completed an in vivo project studying the rat microbiome and effects of intermittent fasting in a monocrotaline rat model of pulmonary arterial hypertension. These data have been published.
She has also been working as Co-PI on another randomized, double-blinded placebo controlled clinical trial studying microbiota transplant therapy and engraftment in ulcerative colitis patients at the University of Minnesota and an additional trial studying fecal microbiota transplant in post-operative Crohn’s disease patients. She is currently completing the microbiome analysis for these trials.

Accomplishments:
First Prize, 2021 ATS Conference BEAR Cage Competition, ATS International Conference, 2021 American Journal of Respiratory and Critical Care Medicine Emerging Investigator, March 2023

Dr. Moutsoglu on PubMed

Trainee 2021-2022

Mentor: Rita Perlingeiro, PhD

Research Project Area/Focus:
Establishment of a non-human primate myogenic model for enabling cell-based therapy for muscle degenerative disorders. Transplanting pluripotent stem cell-derived (PSC) myogenic progenitors in a large animal model is critical to evaluate feasibility of cell-based therapies for muscular dystrophy. ​​To address this, 3 Macaca fascicularis iPS cell lines (Cy0657#5, CyMN.1 and CyMN.2) and applied conditional expression of PAX7, which resulted in robust in vitro myogenic differentiation. Whole transcriptome analysis of NHP-PSC cultures undergoing myogenic specification confirmed the successful sequential induction of mesoderm, paraxial mesoderm and myogenic lineages, respectively. Pilot in vivo studies with CyMN.2 Pax7-induced myogenic progenitors show that these cells contribute to muscle regeneration upon transplantation into cardiotoxin-injured muscles of immunocompromised mice. Testing in Macaca fascicularis recipients will provide insights to define key aspects associated with cell delivery in larger muscles and investigate the interaction between donor cells and the host immune system.

Accomplishments:
Travel Award for the 2021 Frontiers in Myogenesis Conference

Dr. Baik on PubMed

Trainee 2022-2024

Mentor: Rita Perlingeiro, PhD

Research Project Area/Focus:
Exploring the dichotomous role of collagen deposition in iPSC-derived skeletal muscle and cardiac transplants
Characterizing how the adult environment impacts the maturation of human and mouse PSC-derived iPAX7/3 myogenic progenitors

Dr. Crist on PubMed

Education/Credentials
MD, PhD, Medicine and Physiology, Medical College of Wisconsin

Trainee 2022-2024

Mentor: John Osborn, PhD

Research Project Area/Focus:
Renal denervation for prevention of tacrolimus-induced nephrotoxicity in rats

Accomplishments:
University of Minnesota Department of Surgery Research Week 2022, Second Prize, Clinical/Education Research Category

Dr. Dayton on PubMed

Education/Credentials
Ph.D. in Biomedical Engineering, University of Alabama at Birmingham

Trainee 2022-2025

Mentor: Forum Kamdar, MD, PhD

Research Project Area/Focus:

• Adrenergic Stress and SERCA Upregulation in Duchenne Muscular Dystrophy Cardiomyopathy
• Toward a 3D Human Model of Duchenne Muscular Dystrophy Cardiomyopathy
• Using patient-derived hiPSC-CMs to study mechanisms behind disease progression in DMD cardiomyopathy. A lot of focus is on calcium handling due to the high incidence of arrhythmias in these patients, we are also looking at mitochondrial function since there is little data on cardiac mitochondrial dysfunction in DMD and what there is is in mouse models that don't model the human cardiomyopathy very well. We have been working on incorporating bioprinting & 3D tissue engineering to generate more clinically relevant models, though that has been less of a focus lately as we have been working a lot on troubleshooting & improving that with the help of a newer lab member.

Accomplishments:
UMN Hebbel Research Day Poster Award (2024, 2025)

Dr. Ernst on PubMed