Translational Cardiovascular Research Center - News and Highlights

Center Highlights

• July 28, 2022 – We are pleased to announce that the American Heart Association’s Council on Basic Cardiovascular Sciences (BCVS), has selected Erik Blackwood, PhD, as a finalist for the 2022 Louis N. and Arnold M. Katz Basic Science Research Prize for Early Career Investigators Competition. The finalists represent the best early career investigators of the BCVS and very few research centers ever have an investigator in this competition, making Erik’s achievement is particularly impactful for our new center. Erik will present his research as part of the competition with three other finalists at the upcoming AHA Scientific Sessions meeting in Chicago on November  5–7, 2022.  We hope all TCRC members will attend the competition in-person or virtually.
  • More information about the AHA meeting in Chicago.
     

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  Congratulations to Chris Glembotski, PhD, on being awarded the Department of Internal Medicine Translational Investigator of the Year, honoring him as a faculty member who demonstrates exemplary translational investigation skills and commitment to scholarship. 

• Congratulations to Dr. Blackwood on his multiple awards from the UArizona Sarver Heart Center. Through his research, Dr. Blackwood, a researcher in the Translational Cardiovascular Research Center (TCRC), seeks to understand the molecular underpinnings of both congenital and lifestyle-driven heart failure with the goal of identifying novel therapeutic targets.
   

• Congratulations to Alexandra “Bobbie” Garvin, PhD, a postdoctoral research fellow in the Department of Basic Medical Sciences (BMS) at the University of Arizona College of Medicine – Phoenix. She has been awarded a UArizona Sarver Heart Center grant for her work entitled, “Prohibitin as a Novel Therapeutic Target for Cardiac Fibrosis.”

• April 2022 – Congratulations to TCRC Member, Zhiyu Dai, PhD, who has recently been elected a Fellow of the American Heart Association (FAHA) conferred by the Council on Cardiopulmonary Critical Care, Perioperative and Resuscitation (3CPR).  Fellowship recognizes and awards premium professional members for excellence, innovative and sustained contributions in the areas of scholarship, practice and/or education, and volunteer service within the AHA/ASA.
   
• Alina Bilal, MS, the abstract has been selected for oral presentation at the ISHR World Congress in Berlin (12-15 June 2022) in the Early Career Investigator (ECI) symposium program. Only a small number of submitted abstracts are chosen for oral presentation.
   
• April 7, 2022 – Congratulations to TCRC member and dean of the college Guy Reed, MD, MS, who was awarded a $5.5 million grant from the Flinn Foundation to establish two research faculty positions and support training to further translational research in cardiovascular diseases, neurosciences and mental health.
   
• April 6, 2022 – Congratulations to Dr. Erik Blackwood, whose abstract has been selected for oral presentation at the ISHR World Congress in Berlin (12-15 June 2022) in the main symposium program. Only a small number of submitted abstracts are chosen for oral presentation.
   
• March 21, 2022 – Congratulations to Aina Bilal, MS, who has been awarded an ECI Travel Award to support your attendance at the ISHR World Congress to be held in Berlin on June 12-15, 2022. 
   

• March 20, 2022 – Congratulations to Zhiyu Dai, PhD, who received an NIH RO1 on the "Role of Endothelial SOX17 Deficiency in the Pathogenesis of Pulmonary Hypertension"

• March 14, 2022 – Congratulations to TCRC member, Shirin Doroudgar, PhD, who received a new University of Arizona Health Sciences Career Development Award (CDA), which fosters academic careers in clinical and translational research. This award provides 75 percent salary funding for two years to enable the focused time necessary to ensure research success.  We are especially proud of Dr. Doroudgar’s achievement, as she is the first UArizona CDA awardee at the college over the eight-year tenure of this funding mechanism.
   
• January 15, 2002 – Congratulations to TCRC members Tobias Jakobi, PhD, and Shirin Doroudgar, PhD, on being awarded BIO5 Rapid Grant titled, “Extending the circtools circular RNA software for full-length sequencing,” in the amount of $49,969. 
   
• January 15, 2022 -  Congratulations to TCRC member Tobias Jakobi, PhD, and honorary TCRC member, Amelia Gallitano, MD, PhD, on being awarded a UA BIO5 Rapid Grant Award titled, “A new bioinformatic analysis to develop a diagnostic test for schizophrenia,” in the amount of $50,000. 
   

• Feb 4, 2022 – Congratulations to Dr. Blackwood, who received a 2022 Outstanding Postdoctoral Scholar Award in recognition for innovation in research, research productivity in grants and publications, and leadership, including mentoring and service nationally and internationally.  The competition for this award is open to all postdoctoral fellows at the University of Arizona. Dr. Blackwood is the first-ever recipient of this award at UArizona College of Medicine – Phoenix. Due to a tie, two awards were made this year; in all previous years of this competition, only one award has been made each year.

• January 2022 – Congratulations to Dr. Erik Blackwood, who has been recently awarded both the Irving J. Levinson Memorial Research Award and J.G. Murray Research Award from the University of Arizona Sarver Heart Center. These awards will fund pilot studies testing the therapeutic efficacy of novel ATF6-activating compounds that Dr. Blackwood identified in large swine models of acute myocardial infarction. Dr. Blackwood will perform these large animal studies in collaboration with Dr. Steve Goldman in the hopes of establishing a pipeline for future collaborative large animal experimentation between the Phoenix and Tucson campuses.  Dr. Blackwood was also recently selected as a University of Arizona Bio5 Institute Postdoctoral Fellow. In addition to being named a fellow, this award will support preliminary studies discerning a role for the unfolded protein response in heart failure with preserved ejection fraction (HFpEF) using human induced pluripotent stem cells. This award will also permit Dr. Blackwood to present his research at the 2022 International Society for Heart Research World Congress in Berlin, Germany.
   
• January 2022 – Congratulations to Taben Hale, PhD, who was recently awarded an R01 from the NIH. This grant entitled “Targeting Resident Cardiac Fibroblast Subpopulations for Protection Against Fibrosis” will fund research on identifying targetable pathways for shifting cardiac fibroblasts towards a low activation state. The long-term goal for this work is to prevent the pathological fibrotic remodeling that underlies heart failure.
• January 1, 2022  – Congratulations to Dr. Blackwood on being awarded a UA BIO5 Postdoctoral Fellowship for his proposal, “Molecular Roles for ATF6 and the Unfolded Protein Response in Pathogenesis of Heart Failure with Preserved Ejection Fraction”. This funding will fund Dr. Blackwood’s travel to the International Society for Heart Research (ISHR) in Berlin, Germany in June of 2022, as well as research supplies necessary to perform the proposed studies.

• December 2021 – Nanoliposomes as Potential New Stroke Treatment: Stroke remains a le

  

  ading cause of death and disability among Veterans and the general public. College of Medicine – Phoenix and Phoenix VA researchers led a collaborative group that also included scientists from Midwestern University and Barrow Neurological Institute to develop nanoliposomes (phospholipid nanoparticles) and test their efficacy in reducing stroke injury. They found that the nanoliposomes reduced the amount of brain injury by inducing an antioxidant protective response. The collaborative team was led at the College of Medicine – Phoenix and Phoenix VA by Raymond Migrino, MD,(principal investigator, Department of Internal Medicine) and Jonathan Lifshitz, PhD, (professor of Child Health and director, Translational Neurotrauma Research Program). The study is funded by VA Merit, Department of Defense, and Arizona Alzheimer’s consortium grants and will be presented at the 2021 American Heart Association meeting with simultaneous publication in Stroke journal.

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  December 2021 – Dr. Alexandra Garvin was awarded a Sarver Heart Center grant entitled “Prohibitin as a Novel Therapeutic Target for Cardiac Fibrosis” to investigate the mitochondrial protein prohibitin in the cardiac fibroblast as a novel molecular target for antifibrotic therapy during the progression to heart failure.
   
• December 2021 – Researchers Awarded $8 Million Grant to Study Depression and Cardiovascular Disease: Congratulations to Dr. Taben Hale, associate professor in the Department of Basic Medical Sciences, and Dr. Alexandra Garvin and team. They have been awarded a second year of funding on the Cardiovascular T32 research grant! This speaks to their outstanding productivity over the past year. We're excited to see their continued and innovative studies progress over the next year and look forward to celebrating future successes.
   
• December 2021 -Congratulations to Dr. Erik Blackwood, who was recently elected as the chair of the Early Career Investigator Committee for the International Society for Heart Research. Dr. Blackwood will represent the University of Arizona College of Medicine – Phoenix and the entire North American Section of ISHR in this worldwide cardiovascular research community by being tasked with the planning of the World Congress in Berlin, Germany, in June 2022, as well as coordinating all activities for early career researchers globally.
  • Get involved with the Early Career Investigator activities and learn more about the World Congress by contacting Dr. Blackwood.
     

• December 2021 – Congratulations to Dr. Taben Hale and her collaborators Jill Goldstein, PhD, of Harvard University, and Robert Handa, PhD, from Colorado State University! They were awarded an $8 million NIH grant to study the impact of prenatal stress on the long-term risk of co-morbid depression and heart disease in offspring.

• December 2021 – Congratulations to Dr. Erik Blackwood on his recent receipt of a University of Arizona Post-doctoral Research Development Grant.

• November 2021 – Frontiers in Cardiovascular Medicine — section Heart Failure and Transplantation — just launched the research topic entitled “Edema in Heart Failure with Reduced Ejection Fraction.” Inna Gladysheva, PhD and Ryan D. Sullivan, DVM, LATG, from the TCRC, along with Pierpaolo Pellicori, MD, from the University of Glasgow are serving as guest editors. The goal of this topic is to present and evaluate the mechanisms underlying edema development, which defines the transition from pre-symptomatic to symptomatic heart failure. Original research, reviews and short communications exploring existing and novel modalities for objective edema diagnostics, monitoring and treatment strategies in translational and clinical studies are encouraged for submission. The deadline for an abstract is November 30, 2021; for an invited manuscript, it is March 31, 2022.

• November 1, 2021 – Congratulations to TCRC member Dr. Doroudgar on being awarded a UA Core Facilities Pilot Grant titled “Generation of a Double Transgenic Mouse Model for Cell-type—specific Inducible Endogenous Gene Activation and Repression” in the amount of $20,900.

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  June 10, 2021 – We are happy and honored to announce that Roderick Tung, MD, has been named chief of the Division of Cardiology and director of Cardiovascular Clinical Research for the Department of Internal Medicine at the University of Arizona College of Medicine – Phoenix and Banner – University Medical Center Phoenix. He will also serve as the director of the Cardiovascular Center at Banner – UMC Phoenix. Dr. Tung is an electrophysiologist and is keenly interested in translational cardiovascular research in many areas, such as ventricular tachycardia and atrial fibrillation. We welcome Dr. Tung as an inaugural member of the Translational Cardiovascular Research Center (TCRC) and look forward to many research collaborations in the future.
   
• In April 2021, the center unveiled the cornerstone pieces of equipment in the TCRC Imaging Lab, a Leica TCS SP8 STED super-resolution confocal with white light laser, FALCON/FLIM, and Tau Sense, and a Leica DMi8 S Infinity THUNDER with TIRF module equipped with a stage top incubation chamber for live-cell imaging.

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  March 2021, saw the center welcome its two newest faculty members — Drs. Tobias Jakobi and Shirin Doroudgar. Drs. Doroudgar and Jakobi come to us from one of the largest, most famous universities in Europe — the University of Heidelberg Medical School in Heidelberg, Germany. They have expertise in cell and molecular cardiology, as well as bioinformatics; and they will play key roles in overseeing the clinical stem cell lab and the precision medicine translational data management systems in the center.

Recent Publications

• July 2022 – A study investigating mechanisms of severe pulmonary arterial hypertension by TCRC Member, Dr. Zhiyu Dai, and colleagues was published in the July 2022 issue of The European Respiratory Journal. Bin Liu, Yi Peng, Dan Yi, Narsa Machireddy, Daoyin Dong, Karina Ramirez, Jingbo Dai, Rebecca Vanderpool, Maggie M. Zhu, Zhiyu Dai and You-Yang Zhao, published a peer-reviewed original research article entitled "Endothelial PHD2 deficiency induces nitrative stress via suppression of caveolin-1 in pulmonary hypertension," suggesting that endothelial PHD2 deficiency in progressive obliterative vascular remodeling decreases caveolin-1 expression. This leads to augmented nitrative stress, which contributes to obliterative pulmonary vascular remodeling and severe pulmonary hypertension.

• April A publication by TCRC Member, Dr. Ryan Sullivan and colleagues appeared in the April 2022 issue of Circulation, Emmanuel M. Camors, Alyson H. Roth, Joseph R. Alef, Ryan D. Sullivan, Jason N. Johnson, Enkhsaikhan Purevjav, and Jeffrey A. Towbin, published a peer-reviewed original research article entitled “Progressive Reduction in Right Ventricular Contractile Function Due to Altered Actin Expression in an Aging Mouse Model of Arrhythmogenic Cardiomyopathy.” explored a new knock-in mouse model and its translational validity by comparing phenotypic features to ACM patient cardiac biopsies.
   
• April 2022 issue of the American Journal of Physiology Heart and Circulatory, L. Madhavpeddi, B. Hammond, D.L. Carbone, P. Kang, R.J. Handa and T.M. Hale published a peer-reviewed research paper titled "Impact of angiotensin II receptor antagonism on the sex-selective dysregulation of cardiovascular function induced by in utero dexamethasone exposure." This paper provides research on in utero exposure to glucocorticoids in late gestation programs changes in cardiovascular function. The objective of this study was to determine the degree to which angiotensin II mediates sex-biased changes in autonomic function as well as basal and stress-responsive cardiovascular function following in utero glucocorticoid exposure. 

• March 2022 issue of Scientific Reports, Craig C. Morris, Jacob Ref, Satya Acharya, Kevin J. Johnson, Scott Squire, Tuschar Acharya, Tyler Dennis, Sherry Daugherty, Alice McArthur, Ikeotunye Royal Chinyere, Jen Watson Koevary, Joshua M. Hare, Jordan J. Lancaster, Steven Goldman, and Ryan Avery published a peer-reviewed research paper titled "Free-breathing gradient recalled echo-based CMR in a swine heart failure model." This paper provides research on swine models and the well-established protocols for creating a closed-chest myocardial infarction (MI), as well as protocols for characterization of cardiac function with cardiac magnetic resonance (CMR). This methods manuscript outlines a novel technique in CMR data acquisition utilizing smart-signal gradient recalled echo (GRE)-based array sequences in a free-breathing swine heart failure model allowing for both high spatial and temporal resolution imaging.
   
• March 2022 issue of Pulmonary Circulation, Bin Liu, Dan Yi, Jiakai Pan, Jingbo Dai, Maggie M. Zhu, You-Yang Zhao, S. Paul Oh, Michael B. Fallon, and Zhiyu Dai published a peer-reviewed research paper titled "Suppression of BMP signaling by PHD2 deficiency in Pulmonary Arterial Hypertension." This paper provides their research findings on how they demonstrated that PHD2 deficiency suppresses BMP signaling in the lung endothelial cells, suggesting the novel mechanisms of dysregulated BMP signaling in the development of pulmonary arterial hypertension.
   
• November 2021 issue of the Journal of the American Heart Association, Zhiyu Dai, Jianding Cheng, Bin Liu, Dan Yi, Anlin Feng, Ting Wang, Lingling An, Chen Gao, Yibin Wang, Maggie M. Zhu, Xianming Zhang and You-Zhao published a peer-reviewed research paper titled "Loss of Endothelial Hypoxia Inducible Factor‐Prolyl Hydroxylase 2 Induces Cardiac Hypertrophy and Fibrosis." This paper provides their research findings on how cardiac hypertrophy and fibrosis are common adaptive responses to injury and stress and how they define, for the first time, the unexpected role of endothelial PHD2 deficiency in inducing cardiac hypertrophy and fibrosis in an HIF‐2α–dependent manner.
   
• October 2021 issue of Science Direct, Jessika Iwanski, Sobhi G. Kazmouz, Shuaizhi Li, Ben Stansfield, Tori T. Salem, Samantha Perez-Miller, Toshinobu Kazui, Lipsa Jena, Jennifer L. Uhrlaub, Scott Lick, Janko Nikolich-Žugich, John P. Konhilas, Carol C. Gregorio, May Khanna, Samuel K. Campos, and Jared M. Churko published a peer-reviewed research paper titled "Antihypertensive drug treatment and susceptibility to SARS-CoV-2 infection in human PSC-derived cardiomyocytes and primary endothelial cells." This paper outlines their research findings on pathogenicity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its ability to enter through the membrane-bound angiotensin-converting enzyme 2 (ACE2) receptor.
   
• September 2021 issue of Tissue Engineering Part B: Reviews, Tori Salem, Zachary Frankman, and Jared Churko published a peer-reviewed research paper titled "Tissue engineering techniques for iPSC derived three-dimensional cardiac constructs," which shows how recent developments in applied developmental physiology have provided well-defined methodologies for producing human stem-cell derived cardiomyocytes. Cardiomyocytes produced in this way have become commonplace as cardiac physiology research models. This review provides a readable, broad-reaching and thorough discussion of major factors to consider for the development of cardiovascular tissues from stem cell derived cardiomyocytes.
   
• July 2021 issue of Stem Cells International, Ikeotunye Royal Chinyere, Pierce Bradley, Joshua Uhlorn, Joshua Eason, Saffie Mohran, Giuliana G. Repetti, Sherry Daugherty, Jen Watson Koevary, Steven Goldman and Jordan J. Lancaster published a peer-reviewed research paper titled "Epicardially Placed Bioengineered Cardiomyocyte Xenograft in Immune-Competent Rat Model of Heart Failure." The article presents information on how human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) are under preclinical investigation as a cell-based therapy for heart failure post-myocardial infarction. This study is aimed at confirming the graft therapeutic efficacy in an immune-competent chronic heart failure (CHF) model and providing an evaluation of the in vitro properties of the tissue graft. 
• June 2021 issue of the American Journal of Physiology, Trevor Wendt and Rayna Gonzales published a peer-reviewed research paper titled “Ozanimod, an S1PR 1 ligand, attenuates hypoxia plus glucose deprivation-induced autophagic flux and phenotypic switching in human brain VSM cells." This paper makes an important link between the sphingosine-1-phosphate receptor (S1PR) and the protection of vascular smooth muscle cells in CNS vasculature which could lead to improved treatments for stroke.

• May 18, 2021 issue of Circulation, Alina Bilal, Erik Blackwood, Donna Thuerauf, and Chris Glembotski published a peer-reviewed research paper titled “Optimizing Adeno-Associated Virus Serotype 9 for Studies of Cardiac Chamber–Specific Gene Regulation." The paper describes a new method for regulating gene expression of a chamber-specific manner in the hearts of experimental animals.

• May 2021 issue of the American Journal of Physiology, Kayleigh Marsh, Adrian Arrieta, Donna Thuerauf, Erik Blackwood, Lauren MacDonnell, and Chris Glembotski published a peer-reviewed research paper titled “The peroxisomal enzyme, FAR1, is induced during ER stress in an ATF6-dependent manner in cardiac myocytes.” This paper is one of the first studies of peroxisomes in cardiac myocytes and makes the link between ER stress in the heart and its effects on the function of peroxisomes.>

• April 2021 issue of the International Journal of Molecular Sciences (Special Issue Heart Failure: From Molecular Basis to Therapy.2.0), Ranjana Tripathi, Ryan Sullivan, Tai-Hwang Fan, Radhika Mehta, Inna Gladysheva, and Guy Reed published a peer-review translational research paper titled “A Low-Sodium Diet Boosts Ang (1–7) Production and NO-cGMP Bioavailability to Reduce Edema and Enhance Survival in Experimental Heart Failure”. This paper reports the pathophysiological outcomes (cardiac function, pulmonary and systemic edema, blood pressure, kidney function, survival) and underlining mechanisms of a low-sodium diet on the progression of experimental normotensive dilated cardiomyopathy to symptomatic HFrEF in randomized, blinded pre-clinical trial. The beneficial molecular pathways related outcomes of the low-sodium diet included increases in ACE2, Ang (1–7), NO and cGMP, which acted to compensate for the deleterious effects of systemic classical RAAS activation observed with this diet.

• January 2021 issue of Hypertension, Alexandra M. Garvin, Matthew D. De Both, Joshua S. Talboom, Merry L. Lindsey, Matthew J. Huentelman, and Taben M. Hale published a peer-reviewed research paper titled, “Transient ACE (Angiotensin-Convertine Enzyme) Inhibition Suppresses Future Fibrogenic Capacity and Heterogeneity of Cardiac Fibroblast Subpopulations.” This paper reveals a shift in the resident cardiac fibroblasts toward a lower activation and less fibrogenic state that persists even after stopping angiotensin-converting enzyme inhibitor treatment in hypertensive rats.