News

Hearts and Minds: Symposium Spotlights Cardiovascular-Brain Research

June 20, 2023 by Janet Essman Franz

The Vermont Center for Cardiovascular and Brain Health supports research by early-career scientists who are investigating the mysteries of the heart-brain connection. The researchers are sharing their findings at a symposium on June 15-16 at UVM’s Davis Center.

Osama Harraz holds a three-dimensional model of the Piezo1 protein, which senses frictional forces as blood moves through brain blood vessels.

The cardiovascular system and brain seem to work independently of each other, but growing evidence shows they are critically intertwined. Blood flowing through the body’s network of blood vessels nourishes and cleanses the brain, and factors that damage the heart or blood vessels can injure the brain and increase risks for developing dementia through Alzheimer’s and small vessel diseases of the brain.

In a state-of-the-art biomedical research center at the University of Vermont, a cadre of early career scientists is investigating the mysteries of the heart-brain connection. The researchers — experts in medicine, epidemiology, chemistry, pharmacology, molecular physiology, biophysics, rehabilitation and movement science, and more — shared their findings at the Vermont Center for Cardiovascular and Brain Health (VCCBH) symposium on June 15–16 at UVM’s Davis Center.

Established in 2020 with a $12 million, five-year National Institutes of Health Center of Biomedical Research Excellence (COBRE) grant, the projects cover a multitude of heart- and brain-health issues, including impacts of cardiovascular disease on brain motor function, brain blood flow, and cognitive decline. The VCCBH funding supports the work of researchers with labs in UVM's newly completed Firestone Medical Research Building and across the campus.

A unique aspect of the VCCBH is its emphasis on team-based, interdisciplinary mentorship from senior mentors and peer mentors. This structure also fosters a pipeline of 27 investigators who can replace project directors as they “graduate” from the center and establish their own, independent labs. Co-led by Mark Nelson, Ph.D., University Distinguished Professor and chair of pharmacology, and Mary Cushman, M.D., M.Sc., University Distinguished Professor and a vice chair of medicine, the goal of the center is to expand UVM’s research capacity and support early career investigators exploring cardiovascular and brain health.

“We support young investigators with pilot awards so that they grow the research mission with new grants, attract new students and postdoctoral fellows, and do cutting-edge research here in Vermont,” Nelson said. “We are developing the next generation of world-class researchers on major scientific and health issues. This is good for UVM, for the medical center, and for the community.”

The symposium provided a forum for the researchers to share their work with colleagues and to inspire promising young scientists. “It’s a showcase of the outstanding research being done at UVM on cardiovascular and brain health, with a focus on the next generation of researchers,” said Nelson. “Young people thinking about going into medicine, research, or the corporate world can see what’s going on here.”

Among the work presented was a project conducted by Osama Harraz, Ph.D., assistant professor of pharmacology, whose research focuses on the control of cerebral blood flow and vascular signaling. His presentation, titled “May the Force Be With You: Piezo1 and Cerebral Blood Flow Regulation,” will highlight the role of Piezo1, a protein that lives on the membranes of cells lining the blood vessels, in brain blood flow control. Named for the Greek word for “pressure,” Piezo1 is a receptor for frictional forces as the blood moves through the brain vasculature. Harraz collaborates with Ardem Patapoutian, Ph.D., a professor of neuroscience at Scripps Research and winner of the 2021 Nobel Prize in Medicine for the discovery of Piezo channel proteins. Harraz is interested in genetic mutations of Piezo1, especially among aging people of African descent. 

“One in three African Americans has a mutation of Piezo1, and African Americans have the highest prevalence of hypertension and cardiovascular disease. It makes us wonder if there’s a connection and a therapeutic approach that we can take to prevent disease,” Harraz said.

Harraz recently received a new, $2.9 million grant from the National Heart, Lung, and Blood Institute to study Piezo1 in health and hypertension, which allows him to “graduate” from VCCBH and further establish his research program. He is currently recruiting junior investigators and lab personnel to join his team, which also studies Alzheimer’s disease with funding from the National Institute on Aging.

“I will run an independent lab at UVM – it’s such a great environment, and a collegial group of researchers,” said Harraz, adding that the VCCBH provides “a way for researchers with different backgrounds and interests to work together with a multidisciplinary approach, toward a common goal.”

Pilot grant recipients presenting their projects included Mansour Gergi, M.D., assistant professor of medicine and UVM Cancer Center member, who discussed cardiovascular care in cancer patients. The grant supports Gergi’s research evaluating risks for bleeding and clot formation in cancer patients with cardiovascular disease. “The funding from VCCBH provides me with protected time from clinical responsibilities, so I am able to conduct my research, evaluating whether a cancer diagnosis affects the decision of clinicians to continue blood thinners for cardiovascular indications,” Gergi said.

Pilot grant recipient, Matthew Caporizzo, Ph.D., assistant professor of molecular physiology and biophysics, presented his research investigating the molecular system that regulates diastolic function, the part of the heartbeat where the heart muscle relaxes and expands to fill with blood. Nearly all heart failure patients have some form of diastolic dysfunction, Caporizzo said.

“Our lab uses advanced techniques to characterize the stiffening of diseased hearts and determine the molecules responsible for stiffening in heart disease,” he said. “The VCCBH has been instrumental in helping me develop a new technique to relate changes in the heart's molecular structure to its relaxation and filling performance. … We are excited to test efficacy of new therapeutic approaches.”

Ten pipeline investigators presented their research in eight-minute “Flash Talks.” These included a project by Debora Kamin Mukaz, Ph.D., on “Residential Segregation and Risk of Hypertension in a Biracial Cohort.” Residential segregation refers to the geospatial manifestation of structural racism, or the separation of people into different living areas based on race or ethnicity. A postdoctoral fellow in the Department of Medicine, Mukaz explores links between residential segregation and unfavorable levels of biomarkers for inflammation and coagulation. These biomarkers may indicate hypertension, which is more likely among Black people than white people in the U.S. This research can inform changes that lead to better prevention measures, she said. “It’s a matter of justice. Ultimately, the goal is better policies to eliminate disparities in hypertension.”

The importance of diversity and inclusion in drug clinical trials was the topic of a keynote address by UVM alumnus Andra S. Stevenson, Ph.D.'01, M.P.H., a UVM undergraduate and doctoral alumnus and senior director of global medical affairs for Merck & Co., Inc.

“Lack of data from diverse populations may lead to overlooked differences. I want drugs I’m developing to work on everyone, but they may not. Research has found that some sex, race, and social determinants of health may contribute to outcomes,” Stevenson told the gathered crowd.

A science keynote address by David E. Clapham, M.D., Ph.D., group leader at the Howard Hughes Medical Institute Janelia Research Campus and professor of cardiovascular research and professor emeritus of neurobiology at Harvard Medical School, will highlight the function of smooth muscle, which regulates blood vessel tone and blood flow in the heart.

The symposium also included three poster sessions and a reception at the ECHO, Leahy Center for Lake Champlain in Burlington. 

Learn more about the Vermont Center for Cardiovascular and Brain Health.

View Vermont media coverage of the VCCBH symposium on NBC5.

Of note:

In a recent Nature Methods paper, Doug Taatjes, Ph.D., Director of the Microscopy Imaging Center, and the Center for Biomedical Shared Resources at the Larner College of Medicine, together with colleagues from the international consortium QUAREP-LiMi, proposed a set of standardized community-developed checklists to assist researchers, reviewers, and journal editors with the goal of increasing the clarity and reproducibility of image figures and their analyses. The hope is that many journals will adopt these guidelines as part of their “Instructions for Authors”—providing a succinct and easy to use checklist for authors when compiling images for reproduction and descriptions of image analyses performed. (11/2023) (from the LCOM Newsletter)

Agilent Lab Visit 01.25.2023 editsThe RBP group took a tour of the new Agilent Laboratory for Chemical Analysis in Discovery Hall. "This new lab is a state-of-the-art instrumentation facility available to the UVM and business communities." (2023)

Congratulations to Dr. Arti Shukla, co-author on the manuscript "Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers" published in the journal Cell. Read the paper

Please join Dr. Yvonne Janssen-Heininger in congratulating Wyatt Chia on his successful thesis defense. Congratulations, Dr. Wyatt Chia, Ph.D.!!!

Please join Dr. Vikas Anathy in congratulating Nicolas Chamberlain and Dr. Emily Nakada.

Nicolas Chamberlain a PhD student recently published a paper entitled “Lung epithelial protein disulfide isomerase A3 (PDIA3) plays an important role in influenza infection, inflammation, and airway mechanics” in the journal Redox Biology (PMID 30735910). His abstract to be presented at the American Thoracic Society (ATS) conference was chosen to receive an abstract scholarship. The scholarship includes a full in-training registration to the 2019 ATS International Conference in Dallas, Texas. 

Dr. Emily Nakada was a post-doctoral fellow in our group. Her manuscript entitled “Conjugated bile acids attenuate allergen-induced airway inflammation and hyperresposiveness by inhibiting UPR transducers” has been recently accepted in the journal JCI Insight.

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Please join Dr. Yvonne Janssen-Heininger in congratulating Allison Manuel and Evan Elko.

Dr. Allison Manuel is a post-doctoral fellow in our group.  Her abstract to be presented at the American Thoracic Society conference was chosen to receive an Abstract Scholarship . The scholarship includes a full In-Training Registration to the 2019 ATS International Conference in Dallas, Texas.   

Evan Elko is a PhD student. He just received notice that his F31 NIH application entitled: “Role of peroxiredoxin-4 in Idiopathic Pulmonary Fibrosis”  will be funded.  

Congratulations to Evan and Allison. 

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Christopher Dustin and Caspar Schiifers, students in Dr. Albert van der Vliet's lab, each won a Young Investigator Award for their presentations at the SRFBM conference in Chicago. (Nov 2018)

SRFBM conference 2018

[photo left to right: students:C. Dustin, C. Schiffers, SRFBM president F. Domann, principal investigator A. van der Vliet]


Announcements

Congratulations to Dr. Yvonne Janssen-Heininger, Ph.D., on receiving the Gender Equity Outstanding Achievement in Medicine & Science Award at the 5th Annual Celebration of Gender Equity in Medicine and Science Awards. (3/2024)

Congratulations to Dr. Brian Cunniff, Ph.D., assistant professor of pathology and laboratory medicine, the team in the Cunniff Lab, and industry partner , RS Oncology, on having their novel therapy enter Phase 2 Clinical trials. Read more here Milestone for UVM-developed cancer drug. (2/2024)

Congratulations to Brian Cunniff, Ph.D., Assistant Professor Pathology and Laboratory Medicine, on being awarded a $1.6 million R01 grant by the National Institute of General Medical Sciences to study the role of mitochondrial trafficking in regulating cell migration, a key feature of metastatic tumors. (09/2023) 

Congratulations to the following RBP members on receiving research support funds in April 2023. Recipients were: Yvonne Janssen-Heininger, Ph.D., $15,000 for a joint initiative between RBP, UVM Cancer Center, and faculty in the Department of Chemistry. Megan Tarte $745 for Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Disease Conference. Albert van der Vliet, Ph.D., $14,400 for Redox processes in macrophage activation in IPF. (9/2023)

2-janssenheininger-300x300

A new study Yvonne Janssen-Heininger, Ph.D., professor of pathology and laboratory medicine, and colleagues published in Nature takes a deep dive into unraveling the oxidative vulnerabilities of each of the cysteines of glutaredoxin, which is important in protection from fibrosis but gets inactivated via oxidative mechanisms. The team leveraged computational chemistry approaches and experimental validation using a new assay specifically designed for this purpose. (8/2023- Larner College of Medicine Newsletter)

RBP Retreat Meeting room (2)

RBP elevator pitch winnersWinning team-Project Proposal (2)

A very successful Inaugural Redox Biology and Pathology Retreat was held recently at the Courtyard Marriott in Burlington. The day resulted in new collaborations and connections spanning, medicine, biology, and chemistry. The images show attendees in the meeting space, our individual elevator pitch winners- Dr. Reem Aboushousha, Dr. Rob Hondal, and Maurice Newton, and our $15,000 research project design winning team.(6/2023)           

vandervliet-habibovic420x280A new study by Albert van der Vliet, Ph.D., professor of pathology and laboratory medicine, and a team of University of Vermont (UVM) researchers is honing in on why people with asthma often have worse symptoms if they are obese. This new research demonstrates that the gene DUOX1 likely contributes to the connection between obesity and asthma.  The research was published ahead of print in the American Journal of Physiology-Lung Cellular and Molecular Physiology and was highlighted as an APSselect article for March 2023. Albert van der Vliet, Ph.D., was the senior author on the paper, along with department of pathology and laboratory medicine coauthors Aida Habibovic, lab research technician;Litiele Cruz, Ph.D., visiting scholar; Vikas Anathy, Ph.D., associate professor; University Distinguished Professor Yvonne Janssen-Heininger, Ph.D.; and additional team members and authors from UVM. Read the full LCOM News story LCOM News (4/2023)

Congratulations to the following recipients that received pathology research support funding. Nathaniel Shannon in Brian Cunniff's, Ph.D., lab was awarded $1800 towards the cost of travel to the 2022 Annual Meeting of the Society for Redox Biology and Medicine (SfRBM). Litiele Cruz, Ph.D., and faculty mentor Albert van der Vliet, PhD., were awarded $2622 for her project "Characterization of Laminin Oxidative Modifications by Peroxidasin in Pulmonary Fibrosis". Nels Olson, PhD., MPH., $14,582 for the purchase of an Agilent BioTek 405 TS Touch Microplate Washer, Model 405 TSRS. Ashley Volaric M.D., Joanna Conant M.D., and David Seward, M.D, Ph.D., were awarded $13,680 for their project, "The Effect of Epstein Barr Virus Latency on Cellular DNA Methylation Profile of Diffuse Large B Cell Lymphoma". (3/2023)

Albert in JapanCongratulations to Dr. Albert van der Vliet, Ph.D., professor of pathology and laboratory medicine, for being selected as an Invited Fellow to Tohoku University in Sendai, Japan, to participate in research in the laboratory of Takaaki Akaike, M.D., Ph.D., professor of environmental medicine and molecular toxicology. The invitational fellowship relates to a Tohoku University initiative that allows Tohoku faculty members to host invited researchers to promote collaborative research in the host lab for up to three months. The objective is to promote joint publications and expand international collaborations. Dr. van der Vliet's visit coincided with a medley of scientific meetings and symposia collectively termed  Redox Week In Sendai 2022 and held October 27-November 1, 2022. The events brought together leading scientists from around the world in the specific research fields of nitric oxide biology, polysulfur biochemistry, and biology. Van der Vliet was co-organizer and speaker at one of the symposiums, and Yvonne Janssen-Heininger, Ph.D., and Brian Cunniff, Ph.D., both professors of pathology and laboratory medicine, also participated as invited speakers. Additional Japanese federal funding supports the exchange of invited researchers, graduate students, and post-doctoral scholars to collaborate on research. Read more about the redox research collaboration  between UVM and Tohoku University. (01/2023)

Publications

"P. aeruginosa tRNA-fMet halves secreted in outer membrane vesicles suppress lung inflammation in Cystic Fibrosis." Li Z, Barnaby R, Nymon AB, Roche C, Koeppen K, Ashare A, Hogan DA, Gerber SA, Taatjes DJ, Hampton TH, Stanton BA. American Journal of Physiology. Lung Cellular and Molecular Physiology. 2024 Mar 5. doi: 10.1152/ajplung.00018.2024. Online ahead of print. PMID: 38440830

"Identification of tyrosine brominated extracellular proteins in normal and fibrotic lung tissues." Cruz LC, Habibovic A, Dempsey B, Massafera MP, Janssen-Heininger YMW, Lin MJ, Hoffman ET, Weiss DJ, Huang SK, van der Vliet A, Meotti FC. Redox Biology. 2024 Feb 23;71:103102. doi: 10.1016/j.redox.2024.103102. PMID: 38430684

"ROS production by mitochondria: function or dysfunction?" Palma FR, Gantner BN, Sakiyama MJ, Kayzuka C, Shukla S, Lacchini R, Cunniff B, Bonini MG. Oncogene. 2023 Dec 11. doi: 10.1038/s41388-023-02907-z. Epub ahead of print. PMID: 38081963

"Fingerprint of the oxido-reductase ERO1: A protein disulfide bond producer and supporter of cancer." Zito E, Guarrera L, Janssen-Heininger YMW. Biochimica et biophysica acta. Reviews on Cancer. 2023 Nov 24;1879(1):189027. doi: 10.1016/j.bbcan.2023.189027. Online ahead of print. PMID: 38007054

"Bariatric Surgery Decreases the Capacity of Plasma from Obese Asthmatic Subjects to Augment Epithelial Cell Pro-Inflammatory Cytokine Production." Pena-Garcia PE, Fastiggi VA, Mank MM, Ather JL, Garrow OJ, Anathy V, Dixon AE, Poynter ME. American Jounral of Physiology. Lung Cellular and Molecular Physiology. 2023 Nov 21. doi: 10.1152.ajplung.00205.2023. Online ahead of print. PMID: 37988602

"Marker-based CRISPR screening reveals a MED12-p63 interaction that activates basal identity in pancreatic ductal adenocarcinoma." Maia-Silva D, Schier AC, Skopelitis D, Kechejian V, Alpsoy A, Liverpool J, Taatjes DJ, Vakoc CR. bioRxiv. 2023 Oct 27:2023.10.24.563848. doi: 10.1101/2023.10.24.563848. Preprint. PMID: 37961243

"Glutaredoxin attenuates glutathione levels via deglutathionylation of Otub 1 and subsequent destabilization of system xC." Aboushousha R, van der Velden J, Hamilton N, Peng Z, MacPherson M, Erickson C, White S, Wouters EFM, Reynaert NL, Seward DJ, Li J, Janssen-Heininger YMW. Science Advances. 2023 Sep 15;9(37):eadi5192. doi: 10.1126/sciadv.adi5192. Epub 2023 Sep 13. PMID: 37703360

"Obesity exacerbates influenza-induced respiratory disease via the arachidonic acid-p38 MAPK pathway." Chandrasekaran R, Morris CR, Butzirus IM, Mark ZF, Kumar A, Souza De Lima D, Daphtary N, Aliyeva M, Poynter ME, Anathy V, Dixon AE. Frontiers in Pharmacology. 2023 Aug 23;14:1248873. doi: 10.3389/fphar.2023.1248873. eCollection 2023. PMID: 37680710

"WR1065 conjugated to thiol-PEG polymers as novel anticancer prodrugs: broad spectrum efficacy, synergism, and drug resistance reversal." Walker DM, Lazarova TI, Riesinger SW, Poirer MC, Messier T, Cunniff B, Walker VE. Frontiers in Oncology. 2023 Jul 28;13:1212604. doi: 10.3389/fonc.2023.1212604. PMID: 37576902; MPCID: PMC10419174. h-index: 113

"Structural and functional fine mapping of cysteines in mammalian glutaredoxin reveal their differential oxidation susceptibility." Corteselli EM, Sharafi M, Hondal R, MacPherson M, White S, Lam YW, Gold C, Manuel AM, van der Vliet A, Schneebeli ST, Anathy A, Li J, Janssen-Heininger YMW. Nature Communications. 2023 Jul 28;14(1):4550. doi:10.1038/s41467-023-39664-2. PMID: 37507364; PMCID: PMC10382592. h-index: 449

"Deletion of Miro1 in airway club cells potentiates allergic asthma phenotypes." Bruno S, Lamberty A, McCoy M, Mark Z, Daphtary N, Aliyeva M, Butnor K, Poynter ME, Anathy V, & Cunniff B. Frontiers in Allergy. 2023 4, 1187945. https://doi.org/10.3389/falgy.2023.1187945. H-Index: 4

"Diagnosing calciphylaxis: A series of cases with both imaging and tissue biopsy." Alniemi DT, Kanner C, Stowman AM, Knapp M, McGevna L, Seward DJ, Bui MR. Journal of the American Academy of Dermatology. 2023 May;88(5):1117-1119. doi: 10.1016/j.jaad.2020.05.111. Epub 2020 Jun 8. PMID: 32526323

Corrigendum to "Spatiotemporal higher-order chromatin landscape of human histone gene clusters at Histone Locus Bodies during the cell cycle in breast cancer progression." Ghule PN, Boyd JR, Kabala F, Fritz AJ, Bouffard NA, Gao C, Bright K, Macfarlane J, Seward DJ, Pegraro G, Misteli T, Lian JB, Frietze S, Stein JL, van Wijnen AJ, & Stein GS. [Gene 872 (2023)147441]. Gene 873, 147469 Advance online publication. https://doi.org/10.1016/j.gene.2023.147469

"Spatiotemporal higher-order chromatin landscape of human histone gene clusters at Histone Locus Bodies during the cell cycle in breast cancer progression." Ghule PN, Boyd JR, Kabala F, Fritz AJ, Bouffard NA, Gao C, Bright K, Macfarlane J, Seward DJ, Pegraro G, Misteli T, Lian JB, Frietze S, Stein JL, van Wijnen AJ, & Stein GS. Gene,147441. 2023 Advance online publication. https://doi.org/10.1016/j.gene.2023.147441

"Addressing the Environmental Impact of Science Through a More Rigorous, Reproducible, and Sustainable Conduct of Research." Meyn SM, Ramirez-Aguilar KA, Gregory CW, Mische S, Ott AW, Sol-Church K, Sturges M, Taatjes DJ. Journal of Biomolecular Techniques. 2023 Feb 28;33(4):3fc1f5fe.d085ce95. doi: 10.7171/3fc1f5fe.d085ce95. PMID: 37033093; PMCID:10078834

"Rigor, Reproducibility, and Transparency in Shared Research Resources: Follow-up Survey and Recommendations for Improvement." Journal of Biomolecular Techniques. Ott AW, Sol-Church K, Deshpande GM, Knudtson KL, Meyn SM, Mische SM, Taatjes DJ, Sturges MR, Gregory CW. 2022 Aug 16;33(3):3fc1f5fe.fa789303. doi: 10.7171/3fc1f5fe/fa789303. PMID: 36910580; PMCID: PMC10001929

"Novel post-acquisition image processing to attenuate red blood cell autofluorescence for quantitative image analysis." Epub ahead of print. Bouffard NA, Lee K, DeLance NM, Clason T, Chatterjee N, Taatjes DJ. 2022 Oct 19. doi: 10.1007/s00418-022-02159-0. PMID: 36260111

"Differences in Treatment Response in Bronchial Epithelial Cells from Idiopathic Pulmonary Fibrosis (IPF) Patients: A First Step towards Personalized Medicine?." Antioxidants (Basel). Veith C, Schneider MA, Maas L, van der Vliet A, van Schooten FJ, Kreuter M, Meister M, Boots AW, Kahn N. 2023 Feb 10;12(2):443. doi: 10.3390/antiox12020443. PMID: 36830000; PMCID: PMC9952618

"Diet-Induced Obesity Worsens Allergen-Induced Type 2/Type 17 Inflammation Ain Airways by Enhancing DUOX1 Activation." Habibovic A, Hristova M, Morris CR, Lin MJ, Cruz LC, Ather JL, Geizst M, Anathy, V, Janssen-Heininger YMW, Poynter ME, Dixon AE, van der Vliet A. 2023 Jan 10. doi: 10.1152/ajplung.00331.2022. Epub ahead of print. PMID: 36625485

"In Focus in HCB." Taatjes DJ, Roth J. Histochemistry Cell Biology. 2023 Jan 9:1-3. doi: 10.1007/s00418-022-02176-z. Epub ahead of print. PMID: 36622387; PMCID: PMC9827435

"Mitoquinone mesylate attenuates pathologic features of lean and obese allergic asthma in mice." Chandrasekaran R, Bruno SR, Mark ZF, Walzer J, Caffry S, Gold C, Kumar A, Chamberlain N, Butzirus IM, Morris CR, Daphtary N, Aliyeva M, Lam YM, van der Vliet A, Janssen-Heininger Y, Poynter ME, Dixon AE, Anathy V. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2022 Dec 13. doi: 10.1152/ajplung.00249.2022. Epub ahead of print. PMID: 365151

A recent editorial from Vikas Anathy. Editorial: "Oxidative stress related to cellular metabolism in lung health and diseases." Arunachalam K, Anand K, Palanisamy S, Anathy V. Frontiers in Pharmacology 2022 Nov 3;13:1015423. doi: 10.3389/fphar.2022.1015423. PMID: 36408268; PMCID: PMC9670798