Positions

Overview

  • 1) Vice Chair for Research:
    As Vice Chair for research, I oversee an extensive research portfolio with physician scientists and PhD’s. The current annual NIH funding level is ~$9 million with a total annual funding of ~$18 million, and a total outstanding research funding of ~$60 million. We have advanced this year from 5th to 3rd place in the Blue Ridge NIH rankings for all Academic Anesthesiology Depts. I have been responsible for making critical strategic decisions including scientist recruitment, bridge funding and support, and planning of Research Retreats, and our Research day (~90 poster presentations in 2016). I have been active in guiding mentors and young faculty. I have also been responsible for initiation of a new and successful internal funding mechanism aimed at investing in both young and established investigators that have or are likely to have a track record of success. This has required establishing an internal Departmental “study section”, as well as an infrastructure for accounting and added grants analysis. I have also advanced an initiative to enhance our philanthropic giving through a partnership with our development team and Alumni. This leadership position has given me not only budget management skills, but also an understanding of what is necessary to maintain and grow a research operation at an academic institution. It has also enhanced my understanding of what is needed to support, promote and grow clinician and PhD scientists.

    2) Division Chief of Cardiac Anesthesia:
    I have just stepped down as the division to focus on my role as Vice Chair for Research after appropriate succession planning and after personally recruiting my successor. I have been the Division chief for the previous 5 years. Our group is comprised of 17 uniquely talented faculty with diverse interests and expertise in areas ranging from holistic medicine to the molecular mechanisms and pathobiology of cardiovascular disease such as pulmonary hypertension. We provide anesthesia and transesophageal echocardiographic services for approximately 1500 open cardiac surgery procedures in 4 new cardiac suites, over 250 TAVRs in a hybrid suite, and as well as a numerous interventional electrophysiology procedures in 6 interventional suites, all located in close proximity. Our group alone has over $1.5M of annual funding with over 50 publications / year. I have recruited 5 new faculty to our division as well as my successor from an outside institution. I have streamlined and improved efficiency in operations, and supported increased procedure numbers through communication, negotiation, and co-ordination with cardiac surgeons and cardiologists. I have re-visited and improved call coverage, and matched compensation with work, a process that has enhanced morale amongst our divisional faculty. The most important legacy of my tenure has been the creation of highly trained electrophysiology cohort of CRNAs which now provide over 95% of all anesthetics for EP procedures in 5 EP labs. We have also introduced new technology into the EP Labs including jet ventilation and trans-cutaneous CO2 monitoring, and the level of satisfaction with our service from our cardiologists and patients is extremely high. Additionally, we have initiated research and quality improvement programs in this CRNA cohort. This experience has allowed me to manage, educate, integrate, collaborate with CRNAs who provide a critical role in the anesthesia team of any modern anesthesia dept. It has also allowed me to work with cardiologists who are now critically important in the new minimally invasive/ hybrid model of cardiac intervention which will inevitably become the backbone of our cardiovascular anesthesia work.

    3) Director, Integrated Vascular Biology Research Laboratory:
    I have been the director of an integrated cardiovascular biology laboratory conducting both basic and translational research for over 18 years. I have been continuously funded by the NIH (NIA and NHLBI), NASA (through the National Space Biomedical Research Institute), the American Heart Association or FAER, as well as other foundations (for the scope of research activities see RESEARCH section). I believe this has given me a keen sense of what is required to be successful in securing funding from diverse sources. It has also taught me fiscal responsibility in the context of grant financial management. Additionally, it has highlighted for me the importance of mentoring- a key to continuity. Most importantly, I understand what is needed to be successful as a researcher, and how important it is to invest in, and commit resources to the right young people early in their careers.

    4) Johns Hopkins International, ARAMCO Health Care Cardiovascular Team:
    I have been an integral member of the Johns Hopkins Aramco Health Care Cardiovascular Team which launched a new Cardiac Surgery Program on April 16th of this year at the Hopkins/Aramco hospital in Dhahran, Eastern Province, Saudi Arabia. This project has spanned almost 3 years and included an initial visit and comprehensive assessment of feasibility, planning, training, recruitment and observerships for cardiac surgeons and cardiac anesthesia colleagues. This process has taught me cultural sensitivity, complexity of organization in international environments, and the importance of persistence and focus toward a goal in the face of headwinds and potential barriers.

    5) Entrepreneurship, Intellectual Property and Commercialization:
    I have been the Scientific co-founder of the biotechnology startup company “Arginetix” (then “Corridor Pharmaceuticals”) that raised close to $28million for the development of a novel class of drugs, arginase inhibitors, for the treatment of diseases in which endothelial dysfunction is a significant component (acquired by Astra-Zeneca 2014). This experience has given me insights into the world of biotechnology, venture funding, and entrepreneurship. Additionally, it has taught me the critical importance of leveraging the most important “asset” that one has in academic medicine: Intellectual Property. I now have a greater understanding of the importance of utilizing this resource to translate our research and potentially fund our discoveries for the future.

    6) Associate Team Leader of the Cardiovascular Alterations Team, National Space Biomedical Research Institute (NSBRI):
    As the Associate team lead for NSBRI from 2010 to 2013, I was an integral part of the NASA and space research community. This experience of directing focused research and priority setting has taught me to manage a group of disparate researchers working outside of their institutions, coordinating and focusing their efforts toward the common goal of improving astronaut cardiovascular health.

    7) Cardiac Anesthesia Fellowship Program Director:
    We have seen our fellowship grow to one of the flagship programs in the country currently with 6 ACGME slots, a robust TEE (and 100% pass rate in the APTE exam) and general didactic program. Moreover, our fellows are integrally involved in presentations at our associated societies such as the SCA and IARS. Many of our past fellows are now successful academic anesthesiologists both at Hopkins and other institutions.

    8) Other Leadership training opportunities:
    In 2011 I was selected for the Johns Hopkins leadership program, facilitated by the Hopkins Talent Managements group. In 2015, I was given the opportunity to be a part of the “Serving Leader Program” (Managed by “Third River Partners”, Pittsburgh PA) in our Department. I have been a member of the Johns Hopkins University conflict of interest committee, and have recently been a part of a number of professorial promotions committees. As Vice Chair for Research of the Dept., I sit on the Medical Research Council of Johns Hopkins School of Medicine. These important leadership opportunities and committees have given me insights into the complex workings of academic research medical institutions.

    • Selected Publications

    Academic Article

    Year Title Altmetric
    2022 Extracellular Vesicles from Women with Severe Preeclampsia Impair Vascular Endothelial Function.  Anesthesia and Analgesia.  134:713-723. 2022
    2022 Intraoperative utilisation of high-resolution data for cerebral autoregulation: a feasibility study.  British Journal of Anaesthesia.  128:e217-e219. 2022
    2021 Light-Mediated Inhibition of Colonic Smooth Muscle Constriction and Colonic Motility via Opsin 3.  Frontiers in Physiology.  12. 2021
    2021 Deciphering the Role of microRNAs in Large-Artery Stiffness Associated With Aging: Focus on miR-181b.  Frontiers in Physiology.  12. 2021
    2021 Acetate, a short-chain fatty acid, acutely lowers heart rate and cardiac contractility along with blood pressure.  Journal of Pharmacology and Experimental Therapeutics.  377:39-50. 2021
    2021 Identification of novel bladder sensory GPCRs.  Physiological Reports.  9. 2021
    2021 Corrigendum to “Role of senescence marker p16INK4A measured in peripheral blood T-lymphocytes in predicting length of hospital stay after coronary artery bypass surgery in older adults” [Exp. Gerontol. 74 (2016) 29–36] (Experimental Gerontology (2016) 74 (29–36), (S0531556515301029), (10.1016/j.exger.2015.12.003)).  Experimental Gerontology.  144. 2021
    2021 Aging and chronic high-fat feeding negatively affect kidney size, function, and gene expression in CTRP1-deficient mice 2021
    2021 Degradation of Premature-miR-181b by the Translin/Trax RNase Increases Vascular Smooth Muscle Cell Stiffness.  Hypertension.  831-839. 2021
    2021 Opsin 3–Gas promotes airway smooth muscle relaxation modulated by G protein receptor kinase 2.  American Journal of Respiratory Cell and Molecular Biology.  64:59-68. 2021
    2021 Role of exosomal microRNA signatures: An emerging factor in preeclampsia-mediated cardiovascular disease.  Placenta.  103:226-231. 2021
    2020 The bio-sonographic index. A novel modality for early detection of acute kidney injury after complex vascular surgery. A protocol for an exploratory prospective study.  PLoS One.  15. 2020
    2020 Mythical metrics and methods: Needed paradigm shift in disease recognition and therapy.  Medical Hypotheses.  141. 2020
    2020 Tentonin 3 as a baroreceptor mechanosensor: Not a stretch.  Journal of Clinical Investigation.  130:3412-3415. 2020
    2020 Novel expression of GABAA receptors on resistance arteries that modulate myogenic tone.  Journal of Vascular Research.  57:113-125. 2020
    2020 Late-onset renal hypertrophy and dysfunction in mice lacking CTRP1 2020
    2020 Assessing renal microvascular reactivity by laser speckle-contrast imaging in angiotensin-II-treated mice.  International Journal of Nephrology and Renovascular Disease.  13:45-51. 2020
    2020 Biomimetic human small muscular pulmonary arteries.  Science Advances.  6. 2020
    2019 Histone deacetylase 6 inhibitor tubastatin A attenuates angiotensin II-induced hypertension by preventing cystathionine γ-lyase protein degradation.  Pharmacological Research.  146. 2019
    2019 Arginase II activity regulates cytosolic Ca2+ level in a p32-dependent manner that contributes to Ca2+-dependent vasoconstriction in native low-density lipoprotein-stimulated vascular smooth muscle cells.  Experimental and Molecular Medicine.  51. 2019
    2019 Airway smooth muscle photorelaxation via opsin receptor activation 2019
    2019 Deletion of the microRNA-degrading nuclease, translin/trax, prevents pathogenic vascular stiffness 2019
    2019 Editorial: Regulation of vascular function by circulating blood.  Frontiers in Physiology.  10. 2019
    2019 Effect of incubation with crystalloid solutions or medications on packed red blood cells.  Transfusion.  59:2643-2651. 2019
    2019 Lysyl oxidase-like 2 depletion is protective in age-associated vascular stiffening 2019
    2018 Knockdown of transglutaminase-2 prevents early age-induced vascular changes in mice.  Acta Cirurgica Brasileira.  33:991-999. 2018
    2018 Ischemic Postconditioning and Milrinone.  Journal of Cardiothoracic and Vascular Anesthesia.  32:2149-2151. 2018
    2018 Arginase ii contributes to the Ca2+/CaMKII/eNOS axis by regulating Ca2+ concentration between the cytosol and mitochondria in a p32-dependent manner.  Journal of the American Heart Association.  7. 2018
    2018 Hypoxia Triggers SENP1 (Sentrin-Specific Protease 1) Modulation of KLF15 (Kruppel-Like Factor 15) and Transcriptional Regulation of Arg2 (Arginase 2) in Pulmonary Endothelium 2018
    2018 Imatinib Is Protective Against Ischemia-Reperfusion Injury in an Ex Vivo Rabbit Model of Lung Injury.  Annals of Thoracic Surgery.  105:950-956. 2018
    2018 Pulse wave travel distance as a novel marker of ventricular-arterial coupling 2018
    2018 Relationship between the ambulatory arterial stiffness index and the lower limit of cerebral autoregulation during cardiac surgery.  Journal of the American Heart Association.  7. 2018
    2018 Olfactory, taste, and photo sensory receptors in non-sensory organs: It just makes sense.  Frontiers in Physiology.  9:1-19. 2018
    2018 Opsin 3 and 4 mediate light-induced pulmonary vasorelaxation that is potentiated by G protein-coupled receptor kinase 2 inhibition 2018
    2017 A pulse wave velocity based method to assess the mean arterial blood pressure limits of autoregulation in peripheral arteries.  Frontiers in Physiology.  8. 2017
    2017 Difference between ejection times measured at two different peripheral locations as a novel marker of vascular stiffness.  PLoS One.  12. 2017
    2017 Ejection time: Influence of hemodynamics and site of measurement in the arterial tree.  Hypertension Research.  40:811-818. 2017
    2017 The impact of posture on the cardiac depolarization and repolarization phases of the QT interval in healthy subjects.  Journal of Electrocardiology.  50:640-645. 2017
    2017 MiR-181b regulates vascular stiffness age dependently in part by regulating TGF-β signaling.  PLoS One.  12. 2017
    2017 Role of tissue transglutaminase in age-associated ventricular stiffness.  Amino Acids.  49:695-704. 2017
    2017 Noninvasive assessment of the effect of position and exercise on pulse arrival to peripheral vascular beds in healthy volunteers.  Frontiers in Physiology.  8. 2017
    2017 A special report on the NHLBI initiative to study cellular and molecular mechanisms of arterial stiffness and its association with hypertension.  Circulation Research.  121:1216-1218. 2017
    2017 Cystathionine γ-lyase protects vascular endothelium: A role for inhibition of histone deacetylase 6 2017
    2017 Pilot study: Estimation of stroke volume and cardiac output from pulse wave velocity.  PLoS One.  12. 2017
    2017 Tissue transglutaminase modulates vascular stiffness and function through crosslinking-dependent and crosslinking-independent functions.  Journal of the American Heart Association.  6. 2017
    2017 Validation of a real-time minute-to-minute urine output monitor and the feasibility of its clinical use for patients undergoing cardiac surgery.  Anesthesia and Analgesia.  125:1883-1886. 2017
    2016 Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41.  Physiological Genomics.  48:826-834. 2016
    2016 Arginase Inhibition Reverses Endothelial Dysfunction, Pulmonary Hypertension, and Vascular Stiffness in Transgenic Sickle Cell Mice.  Anesthesia and Analgesia.  123:652-658. 2016
    2016 The Impact of Surgery and Stored Red Blood Cell Transfusions on Nitric Oxide Homeostasis.  Anesthesia and Analgesia.  123:274-282. 2016
    2016 Hibernating squirrels: SIRTin clues for organ protection after ischemia-reperfusion.  Anesthesiology.  124:1215-1217. 2016
    2016 Oxidative stress and rheologic properties of stored red blood cells before and after transfusion to surgical patients.  Transfusion.  56:1101-1111. 2016
    2016 2,3-Diphosphoglycerate Concentrations in Autologous Salvaged Versus Stored Red Blood Cells and in Surgical Patients after Transfusion.  Anesthesia and Analgesia.  122:616-623. 2016
    2016 Role of senescence marker p16INK4a measured in peripheral blood T-lymphocytes in predicting length of hospital stay after coronary artery bypass surgery in older adults.  Experimental Gerontology.  74:29-36. 2016
    2016 MPST but not CSE is the primary regulator of hydrogen sulfide production and function in the coronary artery 2016
    2016 Seeking a blood pressure-independent measure of vascular properties.  Hypertension Research.  39:27-38. 2016
    2016 The Effects of Hemodynamic Changes on Pulse Wave Velocity in Cardiothoracic Surgical Patients.  BioMed Research International.  2016. 2016
    2015 Inhibition of TLR4 attenuates vascular dysfunction and oxidative stress in diabetic rats.  Journal of Molecular Medicine.  93:1341-1354. 2015
    2015 Subacute Hemolysis in Sickle Cell Mice Causes Priapism Secondary to NO Imbalance and PDE5 Dysregulation 2015
    2015 NEDDylation promotes endothelial dysfunction: A role for HDAC2.  Journal of Molecular and Cellular Cardiology.  81:18-22. 2015
    2015 Soluble guanylate cyclase is required for systemic vasodilation but not positive inotropy induced by nitroxyl in the mouse.  Hypertension.  65:385-392. 2015
    2014 Melanopsin mediates light-dependent relaxation in blood vessels 2014
    2014 Measuring ascending aortic stiffness in vivo in mice using ultrasound.  Journal of Visualized Experiments.  2014
    2014 OxLDL Triggers Retrograde Translocation of Arginase2 in Aortic Endothelial Cells via ROCK and Mitochondrial Processing Peptidase.  Circulation Research.  115:450-459. 2014
    2014 Inhibition of glycosphingolipid synthesis ameliorates atherosclerosis and arterial stiffness in apolipoprotein E-/-Mice and rabbits fed a high-fat and -cholesterol diet.  Circulation.  129:2403-2413. 2014
    2014 Effect of isoflurane on myocardial energetic and oxidative stress in cardiac muscle from Zucker diabetic fatty rat.  Journal of Pharmacology and Experimental Therapeutics.  349:21-28. 2014
    2014 Exercise, vascular stiffness, and tissue transglutaminase..  Journal of the American Heart Association.  3. 2014
    2014 Impaired red blood cell deformability after transfusion of stored allogeneic blood but not autologous salvaged blood in cardiac surgery patients.  Anesthesia and Analgesia.  118:1179-1187. 2014
    2014 New insights provided by a comparison of impaired deformability with erythrocyte oxidative stress for sickle cell disease.  Blood Cells, Molecules and Diseases.  52:230-235. 2014
    2014 Nitroprusside inhibits calcium-induced impairment of red blood cell deformability.  Transfusion.  54:434-444. 2014
    2014 Transcriptional regulation of endothelial arginase 2 by histone deacetylase 2 2014
    2013 Contribution of arginase activation to vascular dysfunction in cigarette smoking.  Atherosclerosis.  231:91-94. 2013
    2013 Development of novel arginase inhibitors for therapy of endothelial dysfunction.  Frontiers in Immunology.  4. 2013
    2013 Increased tissue transglutaminase activity contributes to central vascular stiffness in eNOS knockout mice 2013
    2013 Sildenafil Citrate-Restored eNOS and PDE5 Regulation in Sickle Cell Mouse Penis Prevents Priapism Via Control of Oxidative/Nitrosative Stress.  PLoS One.  8. 2013
    2013 A physiologic and biochemical profile of clinically rejected lungs on a normothermic ex vivo lung perfusion platform.  Journal of Surgical Research.  183:75-83. 2013
    2013 Arginase inhibition improves coronary microvascular function and reduces infarct size following ischaemia-reperfusion in a rat model.  Acta Physiologica.  208:172-179. 2013
    2013 Decreased erythrocyte deformability after transfusion and the effects of erythrocyte storage duration.  Anesthesia and Analgesia.  116:975-981. 2013
    2013 Sildenafil citrate protects skeletal muscle of ischemia-reperfusion injury. Immunohistochemical study in rat model.  Acta Cirurgica Brasileira.  28:282-287. 2013
    2013 Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased age.  Experimental Gerontology.  48:128-135. 2013
    2013 Arginase II: atherogenesis beyond enzyme activity..  Journal of the American Heart Association.  2. 2013
    2013 Nitric oxide regulates tissue transglutaminase localization and function in the vasculature.  Amino Acids.  44:261-269. 2013
    2012 Chronic oral administration of the arginase inhibitor 2(S)-amino-6-boronohexanoic Acid (ABH) improves erectile function in aged rats.  Journal of Andrology.  33:1169-1175. 2012
    2012 Erratum: Upregulation of arginase-II contributes to decreased age-related myocardial contractile reserve (European Journal of Applied Physiology (2012) 112 (2933-2941) DOI 10.1007/s00421-011-2257-9).  European Journal of Applied Physiology.  112:4189. 2012
    2012 Vasopressin-mediated enhancement of adrenergic vasoconstriction involves both the tyrosine kinase and the protein kinase C pathways.  Anesthesia and Analgesia.  115:1290-1295. 2012
    2012 Hydrogen sulfide decreases reactive oxygen in a model of lung transplantation.  Journal of Surgical Research.  178:494-501. 2012
    2012 Increased arginase II activity contributes to endothelial dysfunction through endothelial nitric oxide synthase uncoupling in aged mice.  Experimental and Molecular Medicine.  44:594-602. 2012
    2012 Alagebrium in combination with exercise ameliorates age-associated ventricular and vascular stiffness.  Experimental Gerontology.  47:565-572. 2012
    2012 About fACE: Perioperative use of angiotensin-converting enzyme inhibitors.  Circulation.  126:249-251. 2012
    2012 Endothelial nitric oxide synthase mediates cutaneous vasodilation during local heating and is attenuated in middle-aged human skin.  Journal of Applied Physiology.  112:2019-2026. 2012
    2012 Response to the letter by Edwards et al.  Circulation Research.  110. 2012
    2012 Upregulation of arginase-II contributes to decreased age-related myocardial contractile reserve.  European Journal of Applied Physiology.  112:2933-2941. 2012
    2011 Hydrogen sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels.  Circulation Research.  109:1259-1268. 2011
    2011 Vascular stiffness and increased pulse pressure in the aging cardiovascular system.  Cardiology Research and Practice.  1. 2011
    2011 HZE 56Fe-ion irradiation induces endothelial dysfunction in rat aorta: Role of xanthine oxidase.  Radiation Research.  176:474-485. 2011
    2011 S-Nitrosation of arginase 1 requires direct interaction with inducible nitric oxide synthase 2011
    2011 Endothelial arginase II and atherosclerosis.  Korean Journal of Anesthesiology.  61:3-11. 2011
    2011 Phosphodiesterase-5A (PDE5A) is localized to the endothelial caveolae and modulates NOS3 activity.  Cardioscience.  90:353-363. 2011
    2011 Oral atorvastatin therapy restores cutaneous microvascular function by decreasing arginase activity in hypercholesterolaemic humans 2011
    2011 Restoring leptin signaling reduces hyperlipidemia and improves vascular stiffness induced by chronic intermittent hypoxia 2011
    2011 OxLDL-dependent activation of arginase II is dependent on the LOX-1 receptor and downstream RhoA signaling.  Atherosclerosis.  214:279-287. 2011
    2011 Implications of vascular aging.  Anesthesia and Analgesia.  112:1048-1060. 2011
    2011 Upregulation of inducible nitric oxide synthase contributes to attenuated cutaneous vasodilation in essential hypertensive humans..  Hypertension.  58:935-942. 2011
    2010 Early changes in vasoreactivity after simulated microgravity are due to an upregulation of the endothelium-dependent nitric oxide/cGMP pathway.  European Journal of Applied Physiology.  110:395-404. 2010
    2010 Single exposure to radiation produces early anti-angiogenic effects in mouse aorta.  Radiation and Environmental Biophysics.  49:397-404. 2010
    2010 Increased endothelial exocytosis and generation of endothelin-1 contributes to constriction of aged arteries.  Circulation Research.  107:242-251. 2010
    2010 Decreased S-nitrosylation of tissue transglutaminase contributes to age-related increases in vascular stiffness.  Circulation Research.  107:117-125. 2010
    2010 Dietary inhibition of xanthine oxidase attenuates radiation-induced endothelial dysfunction in rat aorta.  Journal of Applied Physiology.  108:1250-1258. 2010
    2010 Effect of intermittent hypoxia on atherosclerosis in apolipoprotein E-deficient mice.  Atherosclerosis.  209:381-386. 2010
    2010 Leptin is essential in maintaining normal vascular compliance independent of body weight.  International Journal of Obesity.  34:203-206. 2010
    2010 β2-adrenergic receptor-coupled phosphoinositide 3-kinase constrains cAMP-dependent increases in cardiac inotropy through phosphodiesterase 4 activation.  Anesthesia and Analgesia.  111:870-877. 2010
    2009 Arginase inhibition restores NOS coupling and reverses endothelial dysfunction and vascular stiffness in old rats.  Journal of Applied Physiology.  107:1249-1257. 2009
    2009 Simulated microgravity-induced aortic remodeling.  Journal of Applied Physiology.  106:2002-2008. 2009
    2009 Sildenafil Inhibits Superoxide Formation and Prevents Endothelial Dysfunction in a Mouse Model of Secondhand Smoke Induced Erectile Dysfunction.  Investigative urology.  181:899-906. 2009
    2009 Increased oxidant activity mediates vascular dysfunction in vibration injury.  Journal of Pharmacology and Experimental Therapeutics.  328:223-230. 2009
    2008 Arginase and vascular aging.  Journal of Applied Physiology.  105:1632-1642. 2008
    2008 Selective fluorescent labeling of S-nitrosothiols (S-FLOS): A novel method for studying S-nitrosation.  Nitric Oxide: Biology and Chemistry.  19:295-302. 2008
    2008 Endothelial arginase II: A novel target for the treatment of atherosclerosis.  Circulation Research.  102:923-932. 2008
    2008 Perioperative blood pressure management: Does central vascular stiffness matter?.  Anesthesia and Analgesia.  107:1103-1106. 2008
    2007 Mitochondrial arginase II constrains endothelial NOS-3 activity 2007
    2007 Pulse pressure is an age-independent predictor of stroke development after cardiac surgery.  Hypertension.  50:630-635. 2007
    2007 Inducible NO synthase-dependent S-nitrosylation and activation of arginase1 contribute to age-related endothelial dysfunction.  Circulation Research.  101:692-702. 2007
    2007 Microgravity and cardiac atrophy: No sex discrimination.  Journal of Applied Physiology.  103:1-2. 2007
    2007 Microgravity-induced changes in aortic stiffness and their role in orthostatic intolerance.  Journal of Applied Physiology.  102:853-858. 2007
    2007 Myocyte nitroso-redox imbalance in sepsis: NO simple answer.  Circulation Research.  100:1-4. 2007
    2006 Impaired shear stress-induced nitric oxide production through decreased NOS phosphorylation contributes to age-related vascular stiffness.  Journal of Applied Physiology.  101:1751-1759. 2006
    2006 Oxidized low-density lipoprotein-dependent endothelial arginase II activation contributes to impaired nitric oxide signaling.  Circulation Research.  99:951-960. 2006
    2006 Response to does arginase activity in vitro represent that in vivo? [2].  Hypertension.  48. 2006
    2006 Arginase modulates myocardial contractility by a nitric oxide synthase 1-dependent mechanism 2006
    2006 Activation of the cardiac ciliary neurotrophic factor receptor reverses left ventricular hypertrophy in leptin-deficient and leptin-resistant obesity 2006
    2006 Knockdown of arginase I restores NO signaling in the vasculature of old rats.  Hypertension.  47:245-251. 2006
    2006 Cardiac myocyte apoptosis is associated with increased DNA damage and decreased survival in murine models of obesity.  Circulation Research.  98:119-124. 2006
    2005 P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: Implications for age-associated vascular dysfunction.  Journal of Molecular and Cellular Cardiology.  39:992-995. 2005
    2005 Simulated microgravity produces attenuated baroreflex-mediated pressor, chronotropic, and inotropic responses in mice 2005
    2005 Leptin repletion restores depressed β-adrenergic contractility in ob/ob mice independently of cardiac hypertrophy 2005
    2004 Neuronal nitric oxide synthase negatively regulates xanthine oxidoreductase inhibition of cardiac excitation-contraction coupling 2004
    2004 Critical role for the α-1B adrenergic receptor at the sympathetic neuroeffector junction.  Hypertension.  44:776-782. 2004
    2004 Apurinic/apyrmidinic endonuclease 1 regulates endothelial NO production and vascular tone.  Circulation Research.  95:902-910. 2004
    2004 Enhanced vasodilatory responses to milrinone in catecholamine-precontracted small pulmonary arteries.  Anesthesia and Analgesia.  98:1618-1622. 2004
    2003 Arginase Reciprocally Regulates Nitric Oxide Synthase Activity and Contributes to Endothelial Dysfunction in Aging Blood Vessels.  Circulation.  108:2000-2006. 2003
    2003 Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice.  Circulation.  108:754-759. 2003
    2003 Nitric oxide regulation of myocardial contractility and calcium cycling: Independent impact of neuronal and endothelial nitric oxide synthases.  Circulation Research.  92:1322-1329. 2003
    2002 Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms.  Nature.  416:337-340. 2002
    2002 Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant male Zucker rats.  Journal of Applied Physiology.  92:2035-2044. 2002
    2002 Impaired pulmonary artery contractile responses in a rat model of microgravity: Role of nitric oxide.  Journal of Applied Physiology.  92:33-40. 2002
    2001 Differential gene expression in a murine model of cancer cachexia 2001
    2001 Hindlimb unweighting affects rat vascular capacitance function 2001
    2001 Overview of the perioperative management of the patient with primary pulmonary hypertension.  Problems in Anesthesia.  13:224-239. 2001
    2001 Weight loss is not associated hyperleptinemia in humans pancreatic cancer.  Journal of Clinical Endocrinology and Metabolism.  86:162-166. 2001
    2000 Endogenous circulating sympatholytic factor in orthostatic intolerance.  Hypertension.  36:553-560. 2000
    2000 Reduction of obesity, as induced by leptin, reverses endothelial dysfunction in obese (Lep(ob)) mice.  Journal of Applied Physiology.  89:2382-2390. 2000
    2000 The effects of hindlimb unweighting on the capacitance of rat small mesenteric veins.  Journal of Applied Physiology.  89:2073-2077. 2000
    2000 β3-adrenoceptor deficiency blocks nitric oxide-dependent inhibition of myocardial contractility.  Journal of Clinical Investigation.  106:697-703. 2000
    1999 Subtype specific regulation of human vascular α1-adrenergic receptors by vessel bed and age.  Circulation.  100:2336-2343. 1999
    1999 Pulmonary vascular endothelial responses are differentially modulated after cardiopulmonary bypass.  Journal of Cardiovascular Pharmacology.  34:518-525. 1999
    1999 Brachydactyly type B with its distinct facies and 'cooks syndrome' are the same entity.  Clinical Dysmorphology.  8:41-45. 1999
    1999 Effect of leptin deficiency on metabolic rate in ob/ob mice.  American Journal of Physiology.  276. 1999
    1999 Leptin prevents respiratory depression in obesity.  American Journal of Respiratory and Critical Care Medicine.  159:1477-1484. 1999
    1999 Molecular biology in cardiovascular anesthesiology: The brave new frontier.  Journal of Cardiothoracic and Vascular Anesthesia.  13:744-751. 1999
    1998 Endotoxin-induced alteration in the expression of leptin and β3-adrenergic receptor in adipose tissue.  American Journal of Physiology.  274. 1998
    1998 Endotoxin-induced alteration in the expression of leptin and β3- adrenergic receptor in adipose tissue.  American Journal of Physiology.  274. 1998
    1997 Endotoxin induced transcriptional regulation of leptin and beta-3 adrenergic receptor (b3AR) in mouse adipose tissue 1997
    1997 Beta-3 adrenoceptor (beta-3AR) expression in leptin treated ob/ob mice.  Life Sciences.  61:59-64. 1997
    1996 Role of the β3-adrenergic receptor locus in obesity and noninsulin- dependent diabetes among members of Caucasian families with a diabetic sibling pair.  Journal of Clinical Endocrinology and Metabolism.  81:4422-4427. 1996
    1996 Hypotension resistant to therapy with α receptor agonists complicating cardiopulmonary bypass: Lithium as a potential cause.  Anesthesia and Analgesia.  82:1082-1085. 1996
    1995 Distribution of β3-adrenoceptor mRNA in human tissues.  European Journal of Pharmacology.  289:223-228. 1995
    1995 Constitutive Nitric Oxide Synthase Is Expressed and Nitric Oxide-Mediated Relaxation Is Preserved in Retrieved Human Aortocoronary Vein Grafts.  Journal of Surgical Research.  58:732-738. 1995
    1994 Expression of α1-adrenergic receptor subtype mRNA in rat tissues and human SK-N-MC neuronal cells: Implications for α1-adrenergic receptor subtype classification.  Molecular Pharmacology.  46:221-226. 1994
    1994 Localization of mRNA for three distinct α1-adrenergic receptor subtypes in human tissues: Implications for human α-adrenergic physiology.  Molecular Pharmacology.  45:171-175. 1994
    1994 Endothelins: Biochemistry and pathophysiologic actions.  Anesthesiology.  80:892-905. 1994
    1994 Localization of messenger RNA for three distinct α2-adrenergic receptor subtypes in human tissues: Evidence for species heterogeneity and implications for human pharmacology.  Anesthesiology.  81:1235-1244. 1994

    Chapter

    Year Title Altmetric
    2018 Pharmacology of Anesthetic Drugs.  112-131. 2018
    2010 The disappearing left ventricle: A double lung transplant in a patient with severe pulmonary hypertension.  391-396. 2010

    Research Overview

  • Basic and Translational Research:
    My laboratory has been studying the mechanisms contributing to the pathobiology of vascular dysfunction in diseases such as age related systolic hypertension, atherosclerosis, radiation and pulmonary hypertension for the last 17 years. This integrated vascular biology laboratory has been continuously funded for 13 years by the NIH, as well as the American Heart Association and NASA through the National Space Biomedical Research Institute. Our vascular research program has attracted undergraduates, from the Johns Hopkins Homewood campus as a result of my joint appointment in the Dept. of Biomedical Engineering. We have also been fortunate to attract and train both Masters and PhD students. and train both MD and PhD Post-doctoral fellows, from the Departments of Anesthesiology, Cardiology and Pulmonary Medicine at Hopkins, and from around the country and the world. Many of the graduate and post-doctoral fellows have received funding through foundations such as the AHA and the Foundation for Anesthesia Education and Research (FAER). The majority of mentees have gone on to productive and successful careers in academic medicine, basic and translational science, and industry. It is our goal to continue to train the best academicians in cardiovascular biology such that this next generation of clinician and basic scientists will be able to address the medical needs and challenges of the rising cardiovascular burden. Our major contributions to science include 1) Arginase 1 and its contribution to age-related endothelial dysfunction and vascular stiffness. We were the first to demonstrate that arginase in endothelial cells reciprocally regulates nitric oxide production leading to eNOS uncoupling and endothelial dysfunction and vascular disease. This has led to the emergence of a robust literature on arginase upregulation and vascular disease. It has also led to the development of small molecule inhibitors of arginase for therapy of diseases in which endothelial dysfunction is a significant component. 2) Arginase 2 as a novel target in atherosclerosis: As with age-related endothelial dysfunction we described the mechanisms by which upregulation of arginase 2 by atherogenic stimuli such a as OxLDL through the Lox-1 receptor contributes to atherosclerosis. 3) Radiation induced vascular dysfunction: With funding from NASA and the National Space Biomedical Research Institution (through NASA) to explore the role of Galactic cosmic radiation in the context of space flight beyond low earth orbit, we explored the mechanisms of radiation induced endothelial injury and potential countermeasures to attenuate it. Using both conventional gamma radiation and high linear energy transfer radiation (using the NASA Research laboratory beamline at Brookhaven National Labs, Long Island) we determined the importance of Xanthine oxidase as a producer of radiation -induced oxidative stress and dysfunction in the endothelium. 4) Role of tissue transglutaminase (TG2) and other cross-linking matrix enzymes in Age-related vascular stiffness: Vascular stiffness and resultant age-dependent systolic hypertension remains an independent risk factor in cardiovascular disease. The molecular mechanisms underlying vascular stiffness remain incompletely understood. We have identified impaired nitric oxide bioavailability as an important contributor to vascular stiffness. Nitric oxide not only regulates vascular function through alterations in vascular tone but modifies the function of enzymes and other proteins by redox-dependent modification, S-nitrosylation. We have demonstrated that impaired NO bioavailability enhance the activity of the cross-linking enzyme tissue transglutaminase (TG2) which in turn contributes to increases in vascular stiffness. Using a secretome proteomic approach we have identified other enzymes that might contribute to age-related vascular stiffness: 5) Role of Opsins in the regulation of photorelaxation and vascular function: Classic sensory receptors in extrasensory sites and their roles in signal transduction: In a serendipitous finding we have discovered a light activated non-visual opsin, melanopsin (opsin 4 (Opn4))-dependent vasorelaxant pathway which in the presence of a beta adrenergic receptor kinase 1 (ARK 1 or GRK2) inhibitor is profoundly amplified. We have thus characterized an endogenous opsin-mediated, light-activated molecular switch for vasorelaxation that can be targeted for therapy in all diseases in which altered vasoreactivity is a significant pathophysiologic contributor.
    All of these contribution have been or are funded by independent R01’s except for the radiation work which was funded by NASA and the National Space Biomedical Research Institution.


    Clinical Research:
    1) Age-related vascular stiffness and outcomes: As we age, our large conduit vessels (aorta) become stiffer, a process that leads to systolic hypertension. This vascular stiffness is and independent predictor of MACE. While this has been show in the context of patients following MI, stroke and renal dysfunction, the role of vascular stiffness as a predictor of peri-operative outcome has not been explored. Moreover, while chronologic age is immutable, vascular age is modifiable. Using newly developed devices and technique we continue to study the role of vascular stiffness in peri-operative outcomes and explore interventions that might improve vascular “age” and thus peri-operative outcomes.
    2) Red cell health and transfusion: While transfusion is associated with adverse outcomes, the mechanisms underpinning is incompletely understood. Using multiple measures of erythrocyte health including RBC deformability, oxidative stress, NO we continue to explore the effect of storage duration on these metrics.

    • Investigator On

    Education And Training

  • Coronation Hospital, Internship
  • Long Island Jewish Medical Center, Internship
  • Duke Medical Center Anesthesia, Residency
  • Duke Medical Center Cardiac Anesthesia, Postdoctoral Fellowship
  • Long Island Jewish Medical Center Microbiology, Postdoctoral Fellowship
  • South African Institute for Medical Research, Postdoctoral Fellowship
  • Bachelor of Medicine & Surgery (MBBS), University of the Witwatersrand 1984

    • Awards And Honors

    Full Name

  • Dan Berkowitz