Laboratory of Cardiovascular Physiology and Tissue Injury
Contact Information
- Office: (301) 443-4830
- Fax: (301) 480.0257
-
Mailing Address
National Institutes of Health
5625 Fishers Lane, MSC-9413, room 2N-17
Rockville , MD 20852
Overview of the Lab
The Laboratory of Cardiovascular Physiology and Tissue Injury (LCPTI) seeks to understand the cellular and molecular mechanisms of the complex interplay of oxidative/nitrative stress, inflammation, lipid signaling (for example endocannabinoid signaling) and cell death pathways (e.g. poly(ADP)-ribose polymerase) in tissue injury, and to identify new therapeutic targets using clinically relevant animal models of disease (e.g., ischemia reperfusion injury, cardiomyopathies/heart failure, nephropathies, cardiovascular aging, and alcohol induced cardiovascular, liver and kidney injury and neuroinflammation).
View Dr. Pacher's Curriculum Vitae
Lab Members
Selected Publications
Selected from over 390 publications. The full publication list can be found here.
Google Scholar | Orcid ID | AD Scientific Index
PCSK9, A Promising Novel Target for Age-Related Cardiovascular Dysfunction.
Matyas C, Trojnar E, Zhao S, Arif M, Mukhopadhyay P, Kovacs A, Fabian A, Tokodi M, Bagyura Z, Merkely B, Kohidai L, Lajko E, Takacs A, He Y, Gao B, Paloczi J, Lohoff FW, Haskó G, Ding WX, Pacher P. JACC Basic Transl Sci. 2023 Sep 13;8(10):1334-1353. doi: 10.1016/j.jacbts.2023.06.005. eCollection 2023 Oct. PMID: 38094682
Data-driven transcriptomics analysis identifies PCSK9 as a novel key regulator in liver aging.
Arif M, Matyas C, Mukhopadhyay P, Yokus B, Trojnar E, Paloczi J, Paes-Leme B, Zhao S, Lohoff FW, Haskó G, Pacher P. Geroscience. 2023 Oct;45(5):3059-3077. doi: 10.1007/s11357-023-00928-w. Epub 2023 Sep 20.PMID: 37726433
PCSK9 inhibition attenuates alcohol-associated neuronal oxidative stress and cellular injury.
Wagner J, Park LM, Mukhopadhyay P, Matyas C, Trojnar E, Damadzic R, Jung J, Bell AS, Mavromatis LA, Hamandi AM, Rosoff DB, Vendruscolo LF, Koob GF, Pacher P, Lohoff FW.Brain Behav Immun. 2024 Apr 22;119:494-506. doi: 10.1016/j.bbi.2024.04.022. Online ahead of print.PMID: 38657842
A monoacylglycerol lipase inhibitor showing therapeutic efficacy in mice without central side effects or dependence.
Jiang M, Huizenga MCW, Wirt JL, Paloczi J, Amedi A, van den Berg RJBHN, Benz J, Collin L, Deng H, Di X, Driever WF, Florea BI, Grether U, Janssen APA, Hankemeier T, Heitman LH, Lam TW, Mohr F, Pavlovic A, Ruf I, van den Hurk H, Stevens AF, van der Vliet D, van der Wel T, Wittwer MB, van Boeckel CAA, Pacher P, Hohmann AG, van der Stelt M.Nat Commun. 2023 Dec 5;14(1):8039. doi: 10.1038/s41467-023-43606-3.PMID: 38052772
Structural basis of selective cannabinoid CB2 receptor activation.
Li X, Chang H, Bouma J, de Paus LV, Mukhopadhyay P, Paloczi J, Mustafa M, van der Horst C, Kumar SS, Wu L, Yu Y, van den Berg RJBHN, Janssen APA, Lichtman A, Liu ZJ, Pacher P, van der Stelt M, Heitman LH, Hua T.Nat Commun. 2023 Mar 15;14(1):1447. doi: 10.1038/s41467-023-37112-9.PMID: 36922494
Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe.
Gazzi T, Brennecke B, Atz K, Korn C, Sykes D, Forn-Cuni G, Pfaff P, Sarott RC, Westphal MV, Mostinski Y, Mach L, Wasinska-Kalwa M, Weise M, Hoare BL, Miljuš T, Mexi M, Roth N, Koers EJ, Guba W, Alker A, Rufer AC, Kusznir EA, Huber S, Raposo C, Zirwes EA, Osterwald A, Pavlovic A, Moes S, Beck J, Nettekoven M, Benito-Cuesta I, Grande T, Drawnel F, Widmer G, Holzer D, van der Wel T, Mandhair H, Honer M, Fingerle J, Scheffel J, Broichhagen J, Gawrisch K, Romero J, Hillard CJ, Varga ZV, van der Stelt M, Pacher P, Gertsch J, Ullmer C, McCormick PJ, Oddi S, Spaink HP, Maccarrone M, Veprintsev DB, Carreira EM, Grether U, Nazaré M.Chem Sci. 2022 Apr 1;13(19):5539-5545. doi: 10.1039/d1sc06659e. eCollection 2022 May 18.PMID: 35694350
Rajesh M, Mukhopadhyay P, Bátkai S, Arif M, Varga ZV, Mátyás C, Paloczi J, Lehocki A, Haskó G, Pacher P.Geroscience. 2022 Jun;44(3):1727-1741. doi: 10.1007/s11357-022-00565-9. Epub 2022 Apr 22.PMID: 35460032
He Y, Rodrigues RM, Wang X, Seo W, Ma J, Hwang S, Fu Y, Trojnár E, Mátyás C, Zhao S, Ren R, Feng D, Pacher P, Kunos G, Gao B.J Clin Invest. 2021 Feb 1;131(3):e141513. doi: 10.1172/JCI141513.PMID: 33301423
Interplay of cardiovascular mediators, oxidative stress and inflammation in liver disease and its complications.
Matyas C, Haskó G, Liaudet L, Trojnar E, Pacher P.Nat Rev Cardiol. 2021 Feb;18(2):117-135. doi: 10.1038/s41569-020-0433-5. Epub 2020 Sep 30.PMID: 32999450
Development of High-Specificity Fluorescent Probes to Enable Cannabinoid Type 2 Receptor Studies in Living Cells.
Sarott RC, Westphal MV, Pfaff P, Korn C, Sykes DA, Gazzi T, Brennecke B, Atz K, Weise M, Mostinski Y, Hompluem P, Koers E, Miljuš T, Roth NJ, Asmelash H, Vong MC, Piovesan J, Guba W, Rufer AC, Kusznir EA, Huber S, Raposo C, Zirwes EA, Osterwald A, Pavlovic A, Moes S, Beck J, Benito-Cuesta I, Grande T, Ruiz de Martı N Esteban S, Yeliseev A, Drawnel F, Widmer G, Holzer D, van der Wel T, Mandhair H, Yuan CY, Drobyski WR, Saroz Y, Grimsey N, Honer M, Fingerle J, Gawrisch K, Romero J, Hillard CJ, Varga ZV, van der Stelt M, Pacher P, Gertsch J, McCormick PJ, Ullmer C, Oddi S, Maccarrone M, Veprintsev DB, Nazaré M, Grether U, Carreira EM.J Am Chem Soc. 2020 Oct 7;142(40):16953-16964. doi: 10.1021/jacs.0c05587. Epub 2020 Sep 29.PMID: 32902974
Discovery of a NAPE-PLD inhibitor that modulates emotional behavior in mice.
Mock ED, Mustafa M, Gunduz-Cinar O, Cinar R, Petrie GN, Kantae V, Di X, Ogasawara D, Varga ZV, Paloczi J, Miliano C, Donvito G, van Esbroeck ACM, van der Gracht AMF, Kotsogianni I, Park JK, Martella A, van der Wel T, Soethoudt M, Jiang M, Wendel TJ, Janssen APA, Bakker AT, Donovan CM, Castillo LI, Florea BI, Wat J, van den Hurk H, Wittwer M, Grether U, Holmes A, van Boeckel CAA, Hankemeier T, Cravatt BF, Buczynski MW, Hill MN, Pacher P, Lichtman AH, van der Stelt M.Nat Chem Biol. 2020 Jun;16(6):667-675. doi: 10.1038/s41589-020-0528-7. Epub 2020 May 11.PMID: 32393901
Interplay of Liver-Heart Inflammatory Axis and Cannabinoid 2 Receptor Signaling in an Experimental Model of Hepatic Cardiomyopathy.
Matyas C, Erdelyi K, Trojnar E, Zhao S, Varga ZV, Paloczi J, Mukhopadhyay P, Nemeth BT, Haskó G, Cinar R, Rodrigues RM, Ait Ahmed Y, Gao B, Pacher P.Hepatology. 2020 Apr;71(4):1391-1407. doi: 10.1002/hep.30916. Epub 2020 Jan 24.PMID: 31469200
Beyond THC and Endocannabinoids.
Pacher P, Kogan NM, Mechoulam R.Annu Rev Pharmacol Toxicol. 2020 Jan 6;60:637-659. doi: 10.1146/annurev-pharmtox-010818-021441. Epub 2019 Oct 3.PMID: 31580774
Endothelial dysfunction and angiogenesis impairment in the ageing vasculature.
Ungvari Z, Tarantini S, Kiss T, Wren JD, Giles CB, Griffin CT, Murfee WL, Pacher P, Csiszar A.Nat Rev Cardiol. 2018 Sep;15(9):555-565. doi: 10.1038/s41569-018-0030-z.PMID: 29795441
Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis.
Ouyang X, Han SN, Zhang JY, Dioletis E, Nemeth BT, Pacher P, Feng D, Bataller R, Cabezas J, Stärkel P, Caballeria J, LePine Pongratz R, Cai SY, Schnabl B, Hoque R, Chen Y, Yang WH, Garcia-Martinez I, Wang FS, Gao B, Torok NJ, Kibbey RG, Mehal WZ.Cell Metab. 2018 May 1;27(5):1156. doi: 10.1016/j.cmet.2018.04.007.PMID: 29719229
Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly.
Pacher P, Steffens S, Haskó G, Schindler TH, Kunos G.Nat Rev Cardiol. 2018 Mar;15(3):151-166. doi: 10.1038/nrcardio.2017.130. Epub 2017 Sep 14.PMID: 28905873
Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity.
Soethoudt M, Grether U, Fingerle J, Grim TW, Fezza F, de Petrocellis L, Ullmer C, Rothenhäusler B, Perret C, van Gils N, Finlay D, MacDonald C, Chicca A, Gens MD, Stuart J, de Vries H, Mastrangelo N, Xia L, Alachouzos G, Baggelaar MP, Martella A, Mock ED, Deng H, Heitman LH, Connor M, Di Marzo V, Gertsch J, Lichtman AH, Maccarrone M, Pacher P, Glass M, van der Stelt M.Nat Commun. 2017 Jan 3;8:13958. doi: 10.1038/ncomms13958.PMID: 28045021
Alcohol Misuse and Kidney Injury: Epidemiological Evidence and Potential Mechanisms.
Varga ZV, Matyas C, Paloczi J, Pacher P.Alcohol Res. 2017;38(2):283-288.
PARP inhibition protects against alcoholic and non-alcoholic steatohepatitis.
Mukhopadhyay P, Horváth B, Rajesh M, Varga ZV, Gariani K, Ryu D, Cao Z, Holovac E, Park O, Zhou Z, Xu MJ, Wang W, Godlewski G, Paloczi J, Nemeth BT, Persidsky Y, Liaudet L, Haskó G, Bai P, Boulares AH, Auwerx J, Gao B, Pacher P.J Hepatol. 2017 Mar;66(3):589-600. doi: 10.1016/j.jhep.2016.10.023. Epub 2016 Oct 29.PMID: 27984176
Chronic plus binge ethanol feeding induces myocardial oxidative stress, mitochondrial and cardiovascular dysfunction, and steatosis.
Matyas C, Varga ZV, Mukhopadhyay P, Paloczi J, Lajtos T, Erdelyi K, Nemeth BT, Nan M, Hasko G, Gao B, Pacher P.Am J Physiol Heart Circ Physiol. 2016 Jun 1;310(11):H1658-70. doi: 10.1152/ajpheart.00214.2016. Epub 2016 Apr 22.PMID: 27106042
Monoacylglycerol lipase controls endocannabinoid and eicosanoid signaling and hepatic injury in mice.
Cao Z, Mulvihill MM, Mukhopadhyay P, Xu H, Erdélyi K, Hao E, Holovac E, Haskó G, Cravatt BF, Nomura DK, Pacher P.Gastroenterology. 2013 Apr;144(4):808-817.e15. doi: 10.1053/j.gastro.2012.12.028. Epub 2013 Jan 4.PMID: 23295443
Cannabinoid 1 receptor promotes cardiac dysfunction, oxidative stress, inflammation, and fibrosis in diabetic cardiomyopathy.
Rajesh M, Bátkai S, Kechrid M, Mukhopadhyay P, Lee WS, Horváth B, Holovac E, Cinar R, Liaudet L, Mackie K, Haskó G, Pacher P.Diabetes. 2012 Mar;61(3):716-27. doi: 10.2337/db11-0477. Epub 2012 Feb 7.PMID: 22315315
A new cannabinoid CB2 receptor agonist HU-910 attenuates oxidative stress, inflammation and cell death associated with hepatic ischaemia/reperfusion injury.
Horváth B, Magid L, Mukhopadhyay P, Bátkai S, Rajesh M, Park O, Tanchian G, Gao RY, Goodfellow CE, Glass M, Mechoulam R, Pacher P.Br J Pharmacol. 2012 Apr;165(8):2462-78. doi: 10.1111/j.1476-5381.2011.01381.x.PMID: 21449982
Is lipid signaling through cannabinoid 2 receptors part of a protective system?
Pacher P, Mechoulam R.Prog Lipid Res. 2011 Apr;50(2):193-211. doi: 10.1016/j.plipres.2011.01.001. Epub 2011 Feb 2.PMID: 21295074
Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy.
Rajesh M, Mukhopadhyay P, Bátkai S, Patel V, Saito K, Matsumoto S, Kashiwaya Y, Horváth B, Mukhopadhyay B, Becker L, Haskó G, Liaudet L, Wink DA, Veves A, Mechoulam R, Pacher P.J Am Coll Cardiol. 2010 Dec 14;56(25):2115-25. doi: 10.1016/j.jacc.2010.07.033.PMID: 21144973
Nitric oxide and peroxynitrite in health and disease.
Pacher P., Beckman JS, Liaudet L. Physiol Rev. 2007 Jan;87(1):315-424. doi: 10.1152/physrev.00029.2006. PMID: 17237348
The endocannabinoid system as an emerging target of pharmacotherapy.
Pacher P., Bátkai S, Kunos G. Pharmacol Rev. 2006 Sep;58(3):389-462. doi: 10.1124/pr.58.3.2. PMID: 16968947>
Other Lab Resources
Alumni
Visiting Fellows:
- Janos Paloczi Ph.D, 2016-2023, currently Assistant Professor, Louisiana State University
- Csaba Matyas, MD, PhD, 2018 - 2021, (Special volunteer, 2015-2016)
- Eszter Trojnar MD, 2019-2021, (Supplemental Guest Researcher 2018-2019)
- Zoltan Varga, MD, PhD, 2015-2019, currently Vice Chair Dept. of Pharmacology., Semmelweis Univ.
- Balazs Tamas Nemeth, MD, currently Heart and Vascular Center Semmelweis Univ. Cardiologist
- Rajesh Mohanraj Ph.D, 2006-2011, currently Assistant Professor, UAE University
- Sandor Batkai MD, PhD, 2010-2011, currently group leader, University of Hannover
- Katalin Erdelyi, PhD, 2012-2015, currently a research associate at the National Institute of Oncology in Budapest, Hungary
Guest researchers:
- Hao Pan, MD, currently nephrologist in China
- Enrique Guerrero-Beltrán, PhD, currently Postdoctoral Fellow, Universidad Nacional Autónoma de México
- Bela Horvath, MD, PhD, guest researcher (supported by Hungarian NIH), currently Pathology Resident, Cleveland Clinic
- Wen-Shin Lee, MD, 2011-2012
- Enkui Hao, MD, 2011-2012
- Zongxian Cao, MD, PhD,IRTA Fellow 2011-2014
- Yuping Wang, PhD, 2012-2013
- Lisheng Jiang, MD, 2013-2014
- Suxian Zhao MD, 2018-2020
Summer students/special volunteers:
- Lucja Flis, Special volunteer/summer student, 2005
- Anjum Jafri, Research technician, 2005
- Nora Czifra, Student Biological Laboratory Aide, 2006
- Lauren Becker, Summer Intern, 2008
- Vivek Patel, Special volunteer/summer student (Jun 2008 till date)
- Rachael Y. Gao, Special volunteer/summer student 2009 and Summer Intern 2010
- Galin Tanchian, Special volunteer 2010 and Summer Intern 2011
- Malek Kechrid, Student, UMBC and 2011 summer Intern
- Eileen Holovac, Special volunteer/summer student 2011-2014
- Sevil Aliyeva , MD, Special volunteer, 2014
- Mike Nan, Pre-Bac IRTA fellow July 2015 July 2016
- Cody Savage, Post-Bac IRTA Fellow, 2019-2019
Collaborators
- David Wink Ph.D.; Senior Investigator, NCI, Radiology Branch Contact
- Murali Krishna Cherukuri Ph.D.; NCI, Radiology Branch Contact
- George Kunos M.D., Ph.D.; Scientific Director, NIAAA/NIH; Contact
- Byoung Song PhD; Senior Investigator, Unit of Molecular Biology, NIAAA/NIH; Contact
- Esther M. Sternberg M.D., Director Integrative Neural Immune Program Section on Neuroendocrine Immunology & Behavior, NIMH/NIH; Contact
- Bin Gao M.D., Ph.D; Senior Investigator, Laboratory of Liver Disease, NIAAA/NIH; Contact
- Ted Usdin Ph.D.; Senior Investigator, Laboratory of Genetics, National Institute of Mental Health; Contact
- Michael J. Iadarola, M.D., Ph.D., Senior Investigator, Neuronal Gene Expression Unit Pain and Neurosensory Mechanisms Branch, NIDCR
- Prof. Benjamin F. Cravatt, Ph.D., Director, Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, CA; USA; Contact
- Daniel Nomura, Ph.D. University of California at Berkeley; Contact
- Prof Ken Mackie M.D., Department of Psychological and Brain Sciences and Program in Neuroscience; Contact
- Prof. Lucas Liaudet M.D., Critical Care Division, Department of Internal Medicine, University Hospital, Lausanne, Switzerland;
- Prof. Csaba Szabo M.D., Ph.D.; The University of Texas Medical Branch, Galveston; Contact
- Associate Prof. Zoltan Ungvari M.D., Ph.D., University of Oklahoma Health Sciences Center, USA; Contact
- Prof. Irina Obrosova Ph.D.; Division of Nutrition and Chronic Disease; Pennington Biomedical Research Center; Louisiana State University, Baton Rouge, LA 70808;
- Gyorgy Hasko M.D., Ph.D; Department of Surgery, UMD NJ-New Jersey Medical School, Newark, New Jersey; Contact
- Prof. Rohini Kuner; University of Heidelberg, Germany; Contact
- Stefan Engeli and Jens Jordan M.D., Ph.D.; University of Hannover, Germany; Contact
- Sandor Batkai M.D., Ph.D., University of Hannover, Germany; Contact
- Prof. Roger Pertwee Ph.D., University of Aberdeen, UK; Contact
- Dr. Isaac E. Stillman MD, Department of Pathology, Beth Israel Deaconess Medical Center; Contact
- Prof. Aristidis Veves M.D., Ph.D, Beth Israel Deaconess Medical Center, Boston, MA; Contact
- Prof. Aron Lichtman Ph.D., VCU; Contact
- Prof. Raphael Mechoulam Ph.D.; Department of Medicinal Chemistry and Natural Products, Hebrew University Medical Faculty; Contact; Biography