Overview

PhD: Pasteur Institute 1992

Post-doc: UT Southwestern Medical Center ? Dept of Pharmacology- Dallas, TX. (1992-
2000)

Professor with tenure- Dept of Pharmacology Physiology and Neuroscience- New Jersey
Medical School- Rutgers (2014-present)

Education

PHD, 1992, Pasteur Institute (University Paris IV)
M.S., 1987, University Paris IV
B.S., 1985, University Paris IV

Languages

French

Relevant Publications

Crassous PA, Shu P, Huang C, Gordan R, Brouckaert P, Lampe PD, Xie LH, Beuve A. Newly Identified NO-Sensor Guanylyl Cyclase/Connexin 43 Association Is Involved in Cardiac Electrical Function. J Am Heart Assoc. 2017 Dec 21;6(12)

Huang C, Alapa M, Shu P, Nagarajan N, Wu C, Sadoshima J, Kholodovych V, Li H, Beuve A. Guanylyl cyclase sensitivity to nitric oxide is protected by a thiol oxidation-driven interaction with thioredoxin-1. J Biol Chem. 2017 Sep 1;292(35):14362-14370

Beuve A, Wu C, Cui C, Liu T, Jain MR, Huang C, Yan L, Kholodovych V, Li H. Identification of novel S-nitrosation sites in soluble guanylyl cyclase, the nitric oxide receptor. J Proteomics. 2016 Apr 14;138:40-7

Heckler EJ, Crassous PA, Baskaran P, Beuve A. Protein disulfide-isomerase interacts with soluble guanylyl cyclase via a redox-based mechanism and modulates its activity. Biochem J. 2013 May 15;452(1):161-9

Crassous PA, Couloubaly S, Huang C, Zhou Z, Baskaran P, Kim DD, Papapetropoulos A, Fioramonti X, Duran WN, Beuve A. Soluble guanylyl cyclase is a target of angiotensin II-induced nitrosative stress in a hypertensive rat model. Am J Physiol Heart Circ Physiol. 2012

Sayed N, Kim DD, Fioramonti X, Iwahashi T, Duran WN, Beuve A. Nitroglycerin-induced S-nitrosylation and desensitization of soluble guanylyl cyclase contribute to nitrate tolerance. Circ Res. 2008 Sep 12;103(6):606-14

Sayed N, Baskaran P, Ma X, van den Akker F, Beuve A. Desensitization of soluble guanylyl cyclase, the NO receptor, by S-nitrosylation. Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12312-7.

Research in the Beuve laboratory focuses on cell-cell communications and more
precisely, on pathways that involved the two major second messengers, cAMP and cGMP and
the gaseous molecule nitric oxide (NO). Our research program focuses on 2 main
projects:
a) understanding the mechanisms of modulation of soluble guanylyl cyclase (GC1), a heme
containing enzyme that produces cGMP in response to activation by nitric oxide (NO) and
b) the role of GC1 S-nitrosation in cells.

Physiologically, the NO-cGMP signaling pathway is critically involved in vascular
homeostasis via smooth muscle relaxation and in inhibition of platelet aggregation, and
in synaptic plasticity in the nervous system. Pathophysiologically, dysfunction of this
pathway is linked to increased risk of myocardial infarction and is involved in the
development of atherosclerosis, hypercholesterolemia, hypertension, erectile
dysfunction and diabetes mellitus (all characterized by impairment in vascular
reactivity) as well as neurological disorders and retinal degeneration.

We discovered that GC1 is desensitized by S-nitrosation (addition of NO moiety to the
free thiol of cysteine) and investigated the molecular mechanism by which S-nitrosation
affects GC1 activity and the transduction of NO activation. We also found that GC1
forms a complex with thiol-redox proteins, protein disulfide isomerase (PDI) and
thioredoxin 1 (Trx1) and that this association is thiol redox-based. We further
explored the role of the multiple and conserved cysteines (Cys) of GC1 and found that
GC1 could potentially forms disulfide bond, an unexpected post-translational
modification for a cytosolic enzyme.

We use biochemistry, cell biology and integrative approaches to explore the mechanism
of thiol-dependent modulation of GC1 and its involvement in vascular dysfunction under
oxidative and nitrosative stress. Our current research areas are

- Molecular mechanisms of thiol-based modulation of GC1

- Function of the interaction between GC1 and thiol-redox proteins

- Functional studies of thiol-dependent impairment of GC in oxidative pathophysiologies

CURRENT LAB MEMBERS:
Ping Shu (RTS)

Maryam Alapa (PhD student)

Chuanlong (Eric) Cui (PhD student)

CURRENT COLLABORATORS:
Dr. Hong Li
Director, Center for Advanced Proteomics Research, Rutgers
liho2@njms.rutgers.edu

Dr. Vlad Kholodovych
Office of Advanced Research Computing (OARC),Rutgers
vlad.khol@rutgers.edu

Dr. Priya Ray
University of Miami Health System
PRai@med.miami.edu

Dr. Walter Duran
Dpt Pharmacology/Physiology/Neuroscience, Rutgers
duran@njms.rutgers.edu

Dr. Lai-Hua Xie
Department of Cell Biology & Molecular Medicine, Rutgers
xiela@njms.rutgers.edu

CURRENT FUNDING:
National Institutes of Health, R01 GM067640
04/15/2003-03/31/2022
P.I.: Annie Beuve
Regulation of soluble guanylyl cyclase, the NO-receptor
Objectives: Structure/ Function analysis of sGC and mechanisms of modulation.

National Institutes of Health, R01 GM112415
04/01/2015-01/31/2019
P.I.: Annie Beuve (Multi-PI)
NCE 1/30/2020
NO signaling by a Soluble Guanylyl Cyclase-Thioredoxin transnitrosation complex
Objectives: Biological role of a novel discovered function of sGC as transnitrosylase.