Nystoriak Lab

Dr. Matthew Nystoriak is dedicated to understanding how blood flow to the heart is regulated by crosstalk between intermediary metabolism and electrical signals in cells of the vasculature.

News From The Nystoriak Lab

Matthew Nystoriak, Ph.D., has been recruited to Utica and named associate professor of biomedical research and translational medicine at MMRI. In this role, Nystoriak will spearhead a laboratory dedicated to coronary blood flow and cardiovascular medicine.

Areas of Investigation

The overarching research mission of the Nystoriak lab is to improve our understanding of the cellular and molecular underpinnings of cardiovascular health disease.

Cardiovascular aging: The Nystoriak lab focuses on understanding how the heart changes with age. Advanced age is a significant risk factor for declining cardiac function. Ongoing research aims to uncover how alterations in energy metabolism and vascular control of oxygen delivery throughout life may contribute to and accelerate cardiac impairment. The lab tests specific metabolic interventions to restore adequate blood delivery in older individuals, with the goal of preventing or reversing age-related declines in cardiovascular function and exercise tolerance.

Identifying and pursuing new drug targets to treat microvascular diseases: Microvascular dysfunction often leads to poor clinical outcomes, particularly in women. Therapeutic options are limited due to a lack of understanding of the pathophysiological mechanisms. Recent research in the Nystoriak lab has identified proteins that interact with a family of ion channels in blood vessels and function as molecular sensors of oxygen demand in the heart. During moderate or strenuous exercise, as a healthy heart's oxygen consumption and demand increase, these sensors trigger the dilation of small arteries, boosting blood flow instantaneously. The lab is testing the efficacy of small molecules targeting these proteins to enhance the coupling between oxygen supply and demand, offering potential improvements for patients with vasodilator impairment.

Electrical remodeling and arrhythmia: Another focus of the Nystoriak lab is understanding how specific lifestyle factors affect cardiac electrical conduction and rhythmicity. For instance, novel tobacco products such as electronic cigarettes pose significant cardiovascular risks, but the toxicity profiles of many aerosol constituents remain unknown. The lab is investigating how certain chemicals increase the risk of cardiac arrhythmias by directly and indirectly impacting ion channel function and cardiac conduction pathways.

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Lab Focus

Imaging to explore vascular physiology

Dr. Nystoriak looking at a solution

The Nystoriak lab employs diverse in vivo and ex vivo/in vitro imaging techniques to address complex biological questions. This includes state-of-the-art contrast-enhanced ultrasound imaging to quantify tissue perfusion, as well as advanced microscopy to image genetically-encoded fluorescent biosensors that are designed to visualize and quantify cellular levels of second messengers and metabolites.

Single ion channel structure-function relationships

The lab also uses a unique combination of modeling and cellular electrophysiology to explore the relationships between post-translational modifications of ion channel proteins and intermolecular regulation of channel gating behavior.

Scientists looking into microscope
Portrait of Matt Nystoriak

Meet Dr. Matt Nystoriak

Associate Professor of Biomedical Research and Translational Medicine

mnystoriak@mmri.edu

Dr. Nystoriak earned his bachelor’s degree in biology and his Ph.D. in pharmacology at the University of Vermont, College of Medicine in Burlington, Vermont. He then went on to complete his postdoctoral training at the University of Washington and University of California, Davis. Prior to joining MMRI, Nystoriak was an associate professor of Medicine at the University of Louisville, Louisville, Kentucky, in the Center for Cardiometabolic Science. His research has been published in several prestigious scientific journals, including Circulation Research, Nature Communications, Science Signaling and the Journal of Physiology. Nystoriak has also been an invited speaker at several prominent scientific gatherings, including the American Heart Association’s Scientific Sessions, the American Physiology Summit, the UC Davis Cardiovascular Symposium and the World Congress for Microcirculation.

Lab Members

Martin Ezeani MSc PhD

Martin Ezeani, M.Sc., Ph.D.

Postdoctoral Fellow

Ezeani holds an M.Sc. in cellular and molecular neuroscience from the University of Sussex, United Kingdom, UK, and a Ph.D. degree in medicine from Monash University, Australia. Ezeani has two years of experience in cardiovascular research post Ph.D.

2025 Summer Fellows

  • Cooper Borelli
  • Emma Burke

Past Members

Hussein Samarah, 2015-2016
Bhargav Ramesh, 2015-2019
Zachary Wohl, 2016-2020
Linda Harrison, 2016-2018
Mayeesha Ahmed, 2016
Ernesto Pena Calderin, 2016-2018
Marc Dwenger, 2017-2021/2023-2024
Daniel Gomes, 2017
Sean Raph, 2018-2022
Xuemei Hu, 2018-2023
Li Luo, 2019-2024
Emily Hillman, 2020-2022
Laura Martin, 2021
Shannon Green, 2021-2022
Kara Gouwens, 2022-2024
Brennan Aboud-Hall, 2023
Caitlin Wilkerson, 2023-2024
Ning Chen, 2023-2024
Nikita Shah, 2024-2025
Alice Bukrinsky, MD, 2024-2025

Publications

  1. Gouwens, KR, Pena Calderin, E, Okhiria, J, Nguyen, DC, Schulman-Geltzer, EB, Martinez-Ondaro, Y et al.. Cardiac Ketone Body Oxidation Enhances Exercise Performance. Circ Res. 2025;137 (2):350-353. doi: 10.1161/CIRCRESAHA.125.326414. PubMed PMID:40433703 PubMed Central PMC12226228.
  2. Gouwens, KR, Nong, Y, Chen, N, Schulman-Geltzer, EB, Collins, HE, Hill, BG et al.. Myocardial Hyperemia via Cardiomyocyte Catabolism of β-Hydroxybutyrate. Arterioscler Thromb Vasc Biol. 2025;45 (2):341-343. doi: 10.1161/ATVBAHA.124.321848. PubMed PMID:39665139 PubMed Central PMC11869122.
  3. Raph, SM, Calderin, EP, Nong, Y, Brittian, K, Garrett, L, Zhang, D et al.. Kv beta complex facilitates exercise-induced augmentation of myocardial perfusion and cardiac growth. Front Cardiovasc Med. 2024;11 :1411354. doi: 10.3389/fcvm.2024.1411354. PubMed PMID:38978788 PubMed Central PMC11228310.
  4. Huang, L, Cheng, F, Zhang, X, Zielonka, J, Nystoriak, MA, Xiang, W et al.. Nitric oxide synthase and reduced arterial tone contribute to arteriovenous malformation. Sci Adv. 2023;9 (21):eade7280. doi: 10.1126/sciadv.ade7280. PubMed PMID:37235659 PubMed Central PMC10219588.
  5. Raph, SM, Dwenger, MM, Hu, X, Nystoriak, MA. Basal NAD(H) redox state permits hydrogen peroxide-induced mesenteric artery dilatation. J Physiol. 2023;601 (13):2621-2634. doi: 10.1113/JP284195. PubMed PMID:37114864 PubMed Central PMC11714382.
  6. Grandi, E, Navedo, MF, Saucerman, JJ, Bers, DM, Chiamvimonvat, N, Dixon, RE et al.. Diversity of cells and signals in the cardiovascular system. J Physiol. 2023;601 (13):2547-2592. doi: 10.1113/JP284011. PubMed PMID:36744541 PubMed Central PMC10313794.
  7. Verma, N, Velmurugan, GV, Winford, E, Coburn, H, Kotiya, D, Leibold, N et al.. Aβ efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas. Commun Biol. 2023;6 (1):2. doi: 10.1038/s42003-022-04398-2. PubMed PMID:36596993 PubMed Central PMC9810597.
  8. Carll, AP, Arab, C, Salatini, R, Miles, MD, Nystoriak, MA, Fulghum, KL et al.. E-cigarettes and their lone constituents induce cardiac arrhythmia and conduction defects in mice. Nat Commun. 2022;13 (1):6088. doi: 10.1038/s41467-022-33203-1. PubMed PMID:36284091 PubMed Central PMC9596490.
  9. Kuehl, PJ, McDonald, JD, Weber, DT, Khlystov, A, Nystoriak, MA, Conklin, DJ et al.. Composition of aerosols from thermal degradation of flavors used in ENDS and tobacco products. Inhal Toxicol. 2022;34 (11-12):319-328. doi: 10.1080/08958378.2022.2103602. PubMed PMID:35913821 PubMed Central PMC9830633.
  10. Dwenger, MM, Raph, SM, Baba, SP, Moore, JB 4th, Nystoriak, MA. Diversification of Potassium Currents in Excitable Cells via Kvβ Proteins. Cells. 2022;11 (14):. doi: 10.3390/cells11142230. PubMed PMID:35883673 PubMed Central PMC9317154.
  11. Sansbury, BE, Nystoriak, MA, Uchida, S, Wysoczynski, M, Moore, JB 4th. Rigor Me This: What Are the Basic Criteria for a Rigorous, Transparent, and Reproducible Scientific Study?. Front Cardiovasc Med. 2022;9 :913612. doi: 10.3389/fcvm.2022.913612. PubMed PMID:35845053 PubMed Central PMC9283916.
  12. Dwenger, MM, Raph, SM, Reyzer, ML, Lisa Manier, M, Riggs, DW, Wohl, ZB et al.. Pyridine nucleotide redox potential in coronary smooth muscle couples myocardial blood flow to cardiac metabolism. Nat Commun. 2022;13 (1):2051. doi: 10.1038/s41467-022-29745-z. PubMed PMID:35440632 PubMed Central PMC9018695.
  13. Sadri, G, Fischer, AG, Brittian, KR, Elliott, E, Nystoriak, MA, Uchida, S et al.. Collagen type XIX regulates cardiac extracellular matrix structure and ventricular function. Matrix Biol. 2022;109 :49-69. doi: 10.1016/j.matbio.2022.03.007. PubMed PMID:35346795 PubMed Central PMC9161575.
  14. Petri, BJ, Piell, KM, South Whitt, GC, Wilt, AE, Poulton, CC, Lehman, NL et al.. HNRNPA2B1 regulates tamoxifen- and fulvestrant-sensitivity and hallmarks of endocrine resistance in breast cancer cells. Cancer Lett. 2021;518 :152-168. doi: 10.1016/j.canlet.2021.07.015. PubMed PMID:34273466 PubMed Central PMC8358706.
  15. Ohanyan, V, Raph, SM, Dwenger, MM, Hu, X, Pucci, T, Mack, G et al.. Myocardial Blood Flow Control by Oxygen Sensing Vascular Kvβ Proteins. Circ Res. 2021;128 (6):738-751. doi: 10.1161/CIRCRESAHA.120.317715. PubMed PMID:33499656 PubMed Central PMC8486354.
  16. Chilian, W, Nystoriak, MA, Sisakian, H, Ohanyan, V. Coronary microvascular disease during metabolic syndrome: What is known and unknown: Pathological consequences of redox imbalance for endothelial K+ channels. Int J Cardiol. 2020;321 :18-19. doi: 10.1016/j.ijcard.2020.07.020. PubMed PMID:32721413 .
  17. Kilfoil, PJ, Chapalamadugu, KC, Hu, X, Zhang, D, Raucci, FJ Jr, Tur, J et al.. Metabolic regulation of Kv channels and cardiac repolarization by Kvβ2 subunits. J Mol Cell Cardiol. 2019;137 :93-106. doi: 10.1016/j.yjmcc.2019.09.013. PubMed PMID:31639389 PubMed Central PMC7344177.
  18. Nystoriak, MA, Kilfoil, PJ, Lorkiewicz, PK, Ramesh, B, Kuehl, PJ, McDonald, J et al.. Comparative effects of parent and heated cinnamaldehyde on the function of human iPSC-derived cardiac myocytes. Toxicol In Vitro. 2019;61 :104648. doi: 10.1016/j.tiv.2019.104648. PubMed PMID:31518667 PubMed Central PMC7278494.
  19. Syed, AU, Reddy, GR, Ghosh, D, Prada, MP, Nystoriak, MA, Morotti, S et al.. Adenylyl cyclase 5-generated cAMP controls cerebral vascular reactivity during diabetic hyperglycemia. J Clin Invest. 2019;129 (8):3140-3152. doi: 10.1172/JCI124705. PubMed PMID:31162142 PubMed Central PMC6668679.
  20. Jin, L, Jagatheesan, G, Guo, L, Nystoriak, M, Malovichko, M, Lorkiewicz, P et al.. Formaldehyde Induces Mesenteric Artery Relaxation via a Sensitive Transient Receptor Potential Ankyrin-1 (TRPA1) and Endothelium-Dependent Mechanism: Potential Role in Postprandial Hyperemia. Front Physiol. 2019;10 :277. doi: 10.3389/fphys.2019.00277. PubMed PMID:30984013 PubMed Central PMC6448550.
  21. Raph, SM, Bhatnagar, A, Nystoriak, MA. Biochemical and physiological properties of K+ channel-associated AKR6A (Kvβ) proteins. Chem Biol Interact. 2019;305 :21-27. doi: 10.1016/j.cbi.2019.03.023. PubMed PMID:30926318 PubMed Central PMC6584034.
  22. Prada, MP, Syed, AU, Buonarati, OR, Reddy, GR, Nystoriak, MA, Ghosh, D et al.. A Gs-coupled purinergic receptor boosts Ca2+ influx and vascular contractility during diabetic hyperglycemia. Elife. 2019;8 :. doi: 10.7554/eLife.42214. PubMed PMID:30821687 PubMed Central PMC6397001.
  23. Conklin, DJ, Guo, Y, Nystoriak, MA, Jagatheesan, G, Obal, D, Kilfoil, PJ et al.. TRPA1 channel contributes to myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2019;316 (4):H889-H899. doi: 10.1152/ajpheart.00106.2018. PubMed PMID:30735434 PubMed Central PMC6483018.
  24. Nystoriak, MA, Bhatnagar, A. Cardiovascular Effects and Benefits of Exercise. Front Cardiovasc Med. 2018;5 :135. doi: 10.3389/fcvm.2018.00135. PubMed PMID:30324108 PubMed Central PMC6172294.
  25. Nystoriak, MA, Navedo, MF. Regulation of microvascular function by voltage-gated potassium channels: New tricks for an "ancient" dog. Microcirculation. 2018;25 (1):. doi: 10.1111/micc.12435. PubMed PMID:29239491 PubMed Central PMC5826567.
  26. Dwenger, MM, Ohanyan, V, Navedo, MF, Nystoriak, MA. Coronary microvascular Kv1 channels as regulatory sensors of intracellular pyridine nucleotide redox potential. Microcirculation. 2018;25 (1):. doi: 10.1111/micc.12426. PubMed PMID:29110409 PubMed Central PMC5760281.
  27. Nieves-Cintrón, M, Syed, AU, Buonarati, OR, Rigor, RR, Nystoriak, MA, Ghosh, D et al.. Impaired BKCa channel function in native vascular smooth muscle from humans with type 2 diabetes. Sci Rep. 2017;7 (1):14058. doi: 10.1038/s41598-017-14565-9. PubMed PMID:29070899 PubMed Central PMC5656614.
  28. Nieves-Cintrón, M, Syed, AU, Nystoriak, MA, Navedo, MF. Regulation of voltage-gated potassium channels in vascular smooth muscle during hypertension and metabolic disorders. Microcirculation. 2018;25 (1):. doi: 10.1111/micc.12423. PubMed PMID:29044853 PubMed Central PMC5760350.
  29. Morotti, S, Nieves-Cintrón, M, Nystoriak, MA, Navedo, MF, Grandi, E. Predominant contribution of L-type Cav1.2 channel stimulation to impaired intracellular calcium and cerebral artery vasoconstriction in diabetic hyperglycemia. Channels (Austin). 2017;11 (4):340-346. doi: 10.1080/19336950.2017.1293220. PubMed PMID:28631947 PubMed Central PMC5555263.
  30. Nystoriak, MA, Zhang, D, Jagatheesan, G, Bhatnagar, A. Heteromeric complexes of aldo-keto reductase auxiliary KVβ subunits (AKR6A) regulate sarcolemmal localization of KV1.5 in coronary arterial myocytes. Chem Biol Interact. 2017;276 :210-217. doi: 10.1016/j.cbi.2017.03.011. PubMed PMID:28342889 PubMed Central PMC5610061.
  31. Ghosh, D, Syed, AU, Prada, MP, Nystoriak, MA, Santana, LF, Nieves-Cintrón, M et al.. Calcium Channels in Vascular Smooth Muscle. Adv Pharmacol. 2017;78 :49-87. doi: 10.1016/bs.apha.2016.08.002. PubMed PMID:28212803 PubMed Central PMC5439506.
  32. Dai, X, Yan, X, Zeng, J, Chen, J, Wang, Y, Chen, J et al.. Elevating CXCR7 Improves Angiogenic Function of EPCs via Akt/GSK-3β/Fyn-Mediated Nrf2 Activation in Diabetic Limb Ischemia. Circ Res. 2017;120 (5):e7-e23. doi: 10.1161/CIRCRESAHA.117.310619. PubMed PMID:28137917 PubMed Central PMC5336396.
  33. Qian, H, Patriarchi, T, Price, JL, Matt, L, Lee, B, Nieves-Cintrón, M et al.. Phosphorylation of Ser1928 mediates the enhanced activity of the L-type Ca2+ channel Cav1.2 by the β2-adrenergic receptor in neurons. Sci Signal. 2017;10 (463):. doi: 10.1126/scisignal.aaf9659. PubMed PMID:28119465 PubMed Central PMC5310946.
  34. Nystoriak, MA, Nieves-Cintrón, M, Patriarchi, T, Buonarati, OR, Prada, MP, Morotti, S et al.. Ser1928 phosphorylation by PKA stimulates the L-type Ca2+ channel CaV1.2 and vasoconstriction during acute hyperglycemia and diabetes. Sci Signal. 2017;10 (463):. doi: 10.1126/scisignal.aaf9647. PubMed PMID:28119464 PubMed Central PMC5297430.
  35. Nieves-Cintrón, M, Nystoriak, MA, Prada, MP, Johnson, K, Fayer, W, Dell'Acqua, ML et al.. Selective down-regulation of KV2.1 function contributes to enhanced arterial tone during diabetes. J Biol Chem. 2016;291 (10):4912. doi: 10.1074/jbc.A114.622811. PubMed PMID:26945093 PubMed Central PMC4777829.
  36. Nieves-Cintrón, M, Nystoriak, MA, Prada, MP, Johnson, K, Fayer, W, Dell'Acqua, ML et al.. Selective down-regulation of KV2.1 function contributes to enhanced arterial tone during diabetes. J Biol Chem. 2015;290 (12):7918-29. doi: 10.1074/jbc.M114.622811. PubMed PMID:25670860 PubMed Central PMC4367290.
  37. Nystoriak, MA, Nieves-Cintrón, M, Nygren, PJ, Hinke, SA, Nichols, CB, Chen, CY et al.. AKAP150 contributes to enhanced vascular tone by facilitating large-conductance Ca2+-activated K+ channel remodeling in hyperglycemia and diabetes mellitus. Circ Res. 2014;114 (4):607-15. doi: 10.1161/CIRCRESAHA.114.302168. PubMed PMID:24323672 PubMed Central PMC3954117.
  38. Nystoriak, MA, Nieves-Cintrón, M, Navedo, MF. Capturing single L-type Ca(2+) channel function with optics. Biochim Biophys Acta. 2013;1833 (7):1657-64. doi: 10.1016/j.bbamcr.2012.10.027. PubMed PMID:23124113 PubMed Central PMC3574202.
  39. Takeda, Y, Nystoriak, MA, Nieves-Cintrón, M, Santana, LF, Navedo, MF. Relationship between Ca2+ sparklets and sarcoplasmic reticulum Ca2+ load and release in rat cerebral arterial smooth muscle. Am J Physiol Heart Circ Physiol. 2011;301 (6):H2285-94. doi: 10.1152/ajpheart.00488.2011. PubMed PMID:21984539 PubMed Central PMC3233819.
  40. Nystoriak, MA, O'Connor, KP, Sonkusare, SK, Brayden, JE, Nelson, MT, Wellman, GC et al.. Fundamental increase in pressure-dependent constriction of brain parenchymal arterioles from subarachnoid hemorrhage model rats due to membrane depolarization. Am J Physiol Heart Circ Physiol. 2011;300 (3):H803-12. doi: 10.1152/ajpheart.00760.2010. PubMed PMID:21148767 PubMed Central PMC3064296.
  41. Koide, M, Nystoriak, MA, Brayden, JE, Wellman, GC. Impact of subarachnoid hemorrhage on local and global calcium signaling in cerebral artery myocytes. Acta Neurochir Suppl. 2011;110 (Pt 1):145-50. doi: 10.1007/978-3-7091-0353-1_25. PubMed PMID:21116930 PubMed Central PMC3057755.
  42. Koide, M, Nystoriak, MA, Krishnamoorthy, G, O'Connor, KP, Bonev, AD, Nelson, MT et al.. Reduced Ca2+ spark activity after subarachnoid hemorrhage disables BK channel control of cerebral artery tone. J Cereb Blood Flow Metab. 2011;31 (1):3-16. doi: 10.1038/jcbfm.2010.143. PubMed PMID:20736958 PubMed Central PMC3049462.
  43. Nystoriak, MA, Murakami, K, Penar, PL, Wellman, GC. Ca(v)1.2 splice variant with exon 9* is critical for regulation of cerebral artery diameter. Am J Physiol Heart Circ Physiol. 2009;297 (5):H1820-8. doi: 10.1152/ajpheart.00326.2009. PubMed PMID:19717733 PubMed Central PMC2781364.
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Chase Kessinger, Ph.D.

Chase Kessinger, Ph.D.

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