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David A. Tulis, MS, Ph.D., F.A.H.A.

David Tulis

Associate Professor, Department of Physiology

Brody School of Medicine, East Carolina University

tulisd@ecu.edu

Research Interests

Cardiovascular disease (CVD) ranks as the number one killer of Americans and individuals worldwide, yet unfortunately many of the mechanisms that contribute to CVD remain unclear. The primary focus of research in Dr. Tulis' laboratory is identification and characterization of some of the biochemical, molecular, cellular, and functional mechanisms that underlie abnormal blood vessel growth, a major foundation of CVD. Our hope is that through these efforts we will be able to identify novel players in the etiology and/or maintenance of CVD which could then serve as potential therapeutic targets to combat these dreaded diseases.

Cyclic nucleotide signaling is of particular interest in these studies as these events regulate a wide range of homeostatic and pathophysiologic actions. Areas of study in Dr. Tulis' lab include elucidation of cyclic GMP- versus cyclic AMP-dependent processes and identification and characterization of novel upstream and downstream regulatory systems and processes. Biochemical, molecular, cellular, and functional approaches are used including gain-of-function/loss-of-function interventions and in vivo, ex vivo and in vitro models. Results from these studies are expected to shed light on some potentially promising strategies that could be used to minimize the severity of CVD and associated vascular growth disorders and may offer beneficial prospects for further study in basic science research and human-based clinical studies.

Education & Training

Post-doctoral Fellow, Division of Hematology and Oncology, Department of Medicine, Baylor College of Medicine, Houston, TX

Post-doctoral Fellow, Department of Biomedical Engineering, Rice University, Houston, TX

Doctor of Philosophy, Biomedical Sciences (Cardiovascular Sciences Tract), Eastern Virginia Medical School & Old Dominion University, Norfolk, VA

Master of Science, Toxicology (major), Genetics (minor), North Carolina State University, Raleigh

Bachelor of Science, Biology, University of North Carolina at Chapel Hill

Selected Peer-reviewed Manuscripts (past 5 years)

Holt, A.W., Howard, W.E., Ables, E.T., George, S.M., Kukoly, C.A., Rabidou, J.E., Francisco, J.T., Chukwu, A.N., Tulis, D.A.  Making the cut: Innovative methods for optimizing perfusion-based migration assays.  Cytometry Part A (Ms. 16-097; in press).

Stone, J.D., Holt, A.W., Shaver, P.R., Vuncannon, J.R., Tulis, D.A.  AMP-activated protein kinase inhibits arterial smooth muscle cell proliferation in vasodilator-stimulated phosphoprotein-dependent manner.  J. Non-Inv. Vasc. Invest. (in press), 2016.

Holt, A.W., Martin, D.N., Shaver, P.R., Adderley, S.P., Stone, J.D., Joshi, C.N., Francisco, J.T., Lust, R.M., Weidner, D.A., Shewchuk, B.M., Tulis, D.A.  Soluble guanylyl cyclase-activated cyclic GMP-dependent protein kinase inhibits arterial smooth muscle cell migration independent of VASP-Serine 239 phosphorylation.  Cell. Signal. 28: 1364-1379, doi:10.1016/j.cellsig.2016.06.012, 2016.

Stone, J.D., Holt, A.W., Vuncannon, J.R., Brault, J.J., Tulis, D.A.  AMP-activated protein kinase inhibits transforming growth factor-β-mediated vascular smooth muscle cell growth: Implications for a Smad-3-dependent mechanism. Am. J. Physiol. Heart Circ. Physiol. 309: H1251-H1259; doi:10.1152/ajpheart.00846.2014, 2015.

Adderley, S.P., Martin, D.N., Tulis, D.A.  Exchange protein activated by cAMP (EPAC) controls migration of vascular smooth muscle cells in concentration- and time-dependent manner.  Arch. Physiol. 2:2, doi: http://dx.doi.org/10.7243/2055-0898-2-2, 2015.

Joshi, C.N., Tulis, D.A.  Connexins and intercellular communication in arterial growth and remodeling.  Arch. Physiol. 2:1; http://dx.doi.org/10.7243/2055-0898-2-1, 2015.

Johnson, T.L., Tulis, D.A.*, Keeler, B.E., Virag, J.A., Lust, R.M., Clemens, S.C.  The dopamine D3 receptor knockout mouse mimics aging-related changes in autonomic function and cardiac fibrosis.  PLoS ONE 8(8): e74116. doi:10.1371/ journal.pone.0074116, 2013. [* co-first author]

Holt, A.W., Tulis, D.A.  Experimental rat and mouse carotid artery surgery: Injury & remodeling studies. ISRN Minimally Invasive Surgery, Article No. 167407, 10 pages, http://dx.doi.org/10.1155/2013/167407, 2013.

Stone, J.D., Narine, A., Shaver, P.R., Fox, J.C., Vuncannon, J.R., Tulis, D.A.  AMP-activated protein kinase inhibits vascular smooth muscle cell proliferation and migration and vascular remodeling following injury.  Am. J. Physiol. Heart Circ. Physiol. 304: H369-H381, 2013.

Stone, J.D., Narine, A., Tulis, D.A.  Inhibition of vascular smooth muscle growth via signaling crosstalk between AMP-activated protein kinase and cAMP-dependent protein kinase.  Front. Physiol. 3:409.  doi: 10.3389/fphys.2012.00409, 2012.

Joshi, C.N., Martin, D.N., Shaver, P., Madamanchi, C., Muller-Borer, B.J., Tulis, D.A.  Control of vascular smooth muscle cell growth by connexin 43.  Front. Physiol.  3:220; doi: 10.3389/fphys.2012.00220, 2012.

Peyton, K.J., Shebib, A.R., Azam, M.A., Liu, X., Tulis, D.A., Durante, W.  Bilirubin inhibits neointima formation and vascular smooth muscle cell proliferation and migration.  Front. Pharmacol. 3:48; doi: 10.3389/fphar.2012.00048, 2012.

Adderley, S.P., Joshi, C.N., Martin, D.N., Tulis, D.A.  Phosphodiesterases regulate BAY 41-2272-induced VASP phosphorylation in vascular smooth muscle cells. Front. Pharmacol. 3:10; doi:10.3389/fphar.2012.00010, 2012.

Joshi, C.N., Martin, D.N., Fox, C.J., Mendelev, N.N., Brown, T.A., Tulis, D.A.  The soluble guanylate cyclase stimulator BAY 41-2272 inhibits vascular smooth muscle growth through the protein kinase A and protein kinase G pathways.  J. Pharmacol. Exp. Ther. 339: 394-402, 2011.

Selected Peer-reviewed Book Chapters (past 5 years)

Tulis, D.A.  Vasodilators.  Brody’s Human Pharmacology: Mechanism-Based Therapeutics, Chapter 40, Sixth Edition.  Elsevier Publishing (in press), 2016.

Holt, D., de Castro Brás, L., Tulis, D.  Cyclic Nucleotide-driven Protein Kinase Signaling in Arterial Smooth Muscle (Patho)physiology, Coronary Artery Disease – Causes, Symptoms & Treatments, 1st Edition, iCONCEPT Press, Ltd., ISBN:978-1-922227-92-8. iConcept Press, 2016.

Holt, D., Tulis, D.  Vascular Smooth Muscle as a Therapeutic Target in Disease Pathology. Muscle Cell and Tissue, Chapter 1, pp. 3-26, Ed. K. Sakuma, InTech Open Access Publishers, ISBN 978-953-51-2156-5, doi: 10.5772/60878; http://www.intechopen.com/articles/show/title/vascular-smooth-muscle-as-a-therapeutic-target-in-disease-pathology, 2015.

Tulis, D.A.  Novel Cyclic Nucleotide Signals in the Control of Pathologic Vascular Smooth Muscle Growth, Cardiovascular Disease II, 1st Edition, Chapter 9, pp. 175-200, iCONCEPT Press, Ltd., ISBN 978-1-922227-560, https://www.iconceptpress.com/books/042-2-1/cardiovascular-disease-ii/, 2014.

Adderley, S.P., Joshi, C.N., Martin, D.N., Mooney, S., Tulis, D.A.  Multiple Kinase Involvement in the Regulation of Vascular Growth, Advances in Protein Kinases, Chapter 6, pp. 131-150, Ed. G. Da Silva Xavier, InTech Open Access Publishers, ISBN 978-953-51-0633-3, 2012.

NIH PubMed link to registered publications: https://www.ncbi.nlm.nih.gov/pubmed/?term=Tulis+DA

Selected Grants (past 5 years)

Acid-sensing GPCRs in vascular inflammation and growth (Tulis, PI)
NIH/NHBLBI R15 HL135669

Cyclic GMP/Smad3/FoxO3 control of vascular smooth muscle growth (Tulis, PI)
ECU Intramural Research Award, Division of Research, Economic Development and Engagement

Acidosis signaling pathways in diabetic vasculopathy (Tulis, PI)
Brody Brothers Endowment Fund, East Carolina University Medical & Health Sciences Foundation, Seed/Bridge Grant Program

Function and signaling of GPR4 in vascular response to ischemia-related acidosis (Yang, PI; Tulis, Co-I)
American Heart Association, National Affiliate, Scientist Development Grant

The proton-sensing G protein-coupled receptors GPR4 and GPR68 in abnormal vascular growth (Tulis, PI; Yang, Co-I)
Brody School of Medicine, ECU, Seed Grant Program

Role of GPR4 receptor in blood vessels (Yang, PI; Tulis, Co-I)
Brody School of Medicine, ECU, Seed Grant Program

Acidosis signaling pathways in vascular complications of diabetes (Tulis, PI; Yang, Co-I), declined
Interdisciplinary Research Award, Division of Research and Graduate Studies, ECU

Acidosis, hypoxia and glucose deprivation pathways in endothelial inflammation (Yang, PI; Tulis Co-I), declined
Interdisciplinary Research Award, Division of Research and Graduate Studies, ECU

AMP kinase control of vascular growth (Stone, PI; Tulis, Mentor)
American Heart Association, Mid-Atlantic Affiliate, Pre-doctoral Fellowship

Research Supplement to Promote Diversity in Health-Related Research: NO-independent cGMP regulation of vascular remodeling (Tulis, PI)
NIH/NHLBI R01 HL081720-05S1

American Recovery and Reinvestment Act (ARRA) Funds for Administrative Supplement: NO-independent cGMP regulation of vascular remodeling (Tulis, PI)
NIH/NHLBI R01 HL081720-03S2

American Recovery and Reinvestment Act (ARRA) Funds for Administrative Supplement for Students and Science Educators: NO-independent cGMP regulation of vascular remodeling (Tulis, PI)
NIH/NHLBI R01 HL081720-03S1

NO-independent cGMP regulation of vascular remodeling (Tulis, PI)
NIH/NHLBI R01 HL081720

Selected Editorial & Advisory Service (past 5 years)

French Intensive Care Society, Society of Resuscitation of French Language (FICS-SRLF), Grant Reviewer

Center for Scientific Review, National Institutes of Health & The Italian Ministry of Health, Directorate for Health and Technologies Research, Grant Reviewer

American Heart Association Scientific Sessions 2016, Abstract Reviewer

Editorial Board, Journal of Non-Invasive Vascular Investigation, Italian Society for Vascular Investigation

Medical Research Council, United Kingdom Shared Business Services Ltd.; Grant Reviewer

Senior Editor, Archives of Physiology

American Heart Association, National, Innovative Research Grant, Vascular Science 1 Study Section, Chair

Associate Editor, Frontiers in Physiology

Editorial Board, Frontiers in Pharmacology

Editorial Board, Frontiers in Vascular Physiology, Frontiers in Physiology

American Physiological Society, Cardiovascular Section Advocacy Committee

Review Board, Grants and Fellowships, The Wellcome Trust & Royal Society, London, United Kingdom

American Heart Association, National, Innovative Research Grant, Vascular Science 1 Study Section, Co-Chair

American Heart Association, National, Innovative Research Grant, Vascular Regulation & Disease Study Section

Editorial Board, Frontiers in Genomic Physiology, Frontiers in Physiology

Editorial Board, Frontiers in Integrative and Regenerative Pharmacology, Frontiers in Pharmacology

Sigma Delta Epsilon, Graduate Women in Science, National Fellowships Committee; Grant Reviewer