Dr. Gao's Laboratory

RESEARCH INTERESTS

RESEARCH STATEMENT

Physical activity is fundamental for the maintenance of human health. Regular exercise reduces cardiovascular risk and improves disease prognosis. The goal of our laboratory is to elucidate a novel mechanism underpinning exercise-evoked cardiovascular benefits involved in nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and extracellular vesicles (EVs) in skeletal muscle. We hypothesize that, during exercise, contracting muscle generates a mass of reactive oxygen species (ROS), which in turn activate Nrf2 to upregulate a large group of antioxidant enzymes and other cytoprotective proteins. These proteins are packaged into EVs and transported to the remote tissues/organs where antioxidant defenses are enhanced and protective processes occurred.  

 

novel_mechanism_underlying_exercise_benefits.pngNovel mechanism underlying exercise-cardiovascular benefits

 

LAB PERSONNEL

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Anjali Bhat, PhD
Post-doctoral Research Associate

Li Yu, BS
Research Technologist I


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Ved Pendyala
High School Researcher

Research Intern

Sarah Pribil
PhD Student  

 

ALUMNI

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Will Bruening
Medical Student
Summer 2022 Research Intern
Brenden Lofgren
Medical Student
Summer 2022 Research Intern
 

 

 LAB TECHNIQUES

LAB NEWS

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Team Photo

 

As a Principle Investigator (PI)

Skeletal Muscle Nrf2: Exercise-Induced Cardiovascular Protection

DHHS/NIH/NHLBI (R01HL160820)

$2,070,556

 

Chronic Exercise-Induced Skeletal Muscle Functional and Proteomic Adaptation: Role of Nrf2/Keap1

University of Nebraska Medical Center, College of Medicine; Frances E. Lageschulte and Evelyn B. Weese

New Frontiers in Medical Research Fund

$55,000

 

AT2 Receptors in the RVLM: Regulation of Sympathetic Outflow in Heart Failure

DHHS/NIH/NHLBI (R01HL093028)

$1,811,708

 

Sympatho-excitation in chronic heart failure: role of AT1 and AT2 receptors

American Heart Association National Center, Scientist Development Grant (0635007N)

$260,000

 

Sympathetic outflow in heart failure angiotensin II, NO and ROS

American Heart Association Heartland Affiliate, Postdoctoral Fellowship (0425680Z)

$83,000

 

As a Co-investigator (Co-I)

Nrf2 regulation of oxidative stress in heart failure and extra vesicular communication

DHHS/NIH/NHLBI (R01HL153176) (PI-Dr. Irving Zucker)

Role: Co-Investigator for 3.00 Calendar Months

 

Cardiac afferents and renal function in heart failure

DHHS/NIH/NHLBI (R01HL126796) (PI-Dr. Irving Zucker)

Role: Co-Investigator for 1.80 Calendar Months

 

Novel Neural Mechanisms underlying Lung-Heart Pathological Crosstalk

DHHS/NIH/NHLBI (R01HL152160) (PI-Dr. Hanjun Wang)

Role: Co-Investigator for 1.20 Calendar Months

 

Neural Control of the Circulation in Heart Failure

DHHS/NIH/NHLBI (P01-HL62222) (PI-Dr. Irving Zucker)

Li

Role 2: Project 1. Co-Investigator: 1.2 calendar months

 

 

REPRESENTATIVE PUBLICATIONS
(Past two years)

Tian C, Gao L, Rudebush TL, Yu L, Zucker IH (2022). Extracellular Vesicles Regulate Sympatho-Excitation by Nrf2 in Heart Failure. Circ Res. 2022;131:687-700. PMID: 36098045

 

Xia Z, Vellichirammal NN, Han L, Gao L, Boesen EI, Schiller AM, Pellegrino PR, Lisco SJ, Guda C, Zucker IH, Wang HJ (2022). Cardiac Spinal Afferent Denervation Attenuates Renal Dysfunction in Rats With Cardiorenal Syndrome Type 2. JACC Basic Transl Sci. 2022;7:582-596. PMID: 35818505

 

Chen XY, Lin C, Liu GY, Pei C, Xu GQ, Gao L, Wang SZ, Pan YX (2022). ACE2 gene combined with exercise training attenuates central AngII/AT1 axis function and oxidative stress in a prehypertensive rat model. J Appl Physiol (1985). 2022;132:1460-1467. PMID: 35546127

 

Gao L, Wang HJ, Tian C, Zucker IH (2021). Skeletal Muscle Nrf2 Contributes to Exercise-Evoked Systemic Antioxidant Defense Via Extracellular Vesicular Communication. Exerc Sport Sci Rev. 2021;49:213-222. PMID: 33927165

 

Tian C, Gao L, Zucker IH (2021). Regulation of Nrf2 signaling pathway in heart failure: Role of extracellular vesicles and non-coding RNAs. Free Radic Biol Med. 2021;167:218-231. PMID: 33741451

 

Hong J, Adam RJ, Gao L, Hahka T, Xia Z, Wang D, Nicholas TA, Zucker IH, Lisco SJ, Wang HJ (2021).

Macrophage activation in stellate ganglia contributes to lung injury-induced arrhythmogenesis in male rats.

Acta Physiol (Oxf). 2021;232:e13657. PMID: 33817984

 

Abu R, Yu L, Kumar A, Gao L*, Kumar V* (2021). A Quantitative Proteomics Approach to Gain Insight into NRF2-KEAP1 Skeletal Muscle System and Its Cysteine Redox Regulation. Genes (Basel). 2021;12:1655. (*Co-corresponding Author); PMID: 34828261

 

Hong J, Fu S, Gao L, Cai Y, Lazartigues E, Wang HJ (2021). Voltage-gated potassium channel dysfunction in dorsal root ganglia contributes to the exaggerated exercise pressor reflex in rats with chronic heart failure. Am J Physiol Heart Circ Physiol. 2021;321:H461-H474. PMID: 34270374

 

Tian C, Hu G, Gao L, Hackfort BT, Zucker IH (2020). Extracellular vesicular MicroRNA-27a* contributes to cardiac hypertrophy in chronic heart failure. J Mol Cell Cardiol. 2020;143:120-131.PMID: 32370947

 

Gao L*, Kumar V, Vellichirammal NN, Park SY, Rudebush TL, Yu L, Son WM, Pekas EJ, Wafi AM, Hong J, Xiao P, Guda C, Wang HJ, Schultz HD, Zucker IH* (2020). Functional, proteomic and bioinformatic analyses of Nrf2- and Keap1- null skeletal muscle. J Physiol. 2020;598:5427-5451. PMID: 32893883

 

Hong J, Lisco AM, Rudebush TL, Yu L, Gao L, Kitzerow O, Zucker IH, Wang HJ (2020). Identification of Cardiac Expression Pattern of Transient Receptor Potential Vanilloid Type 1 (TRPV1) Receptor using a Transgenic Reporter Mouse Model. Neurosci Lett. 2020;737:135320. PMID: 32841712

 

Tian C, Gao L, Zhang A, Hackfort BT, Zucker IH (2019). Therapeutic Effects of Nrf2 Activation by Bardoxolone Methyl in Chronic Heart Failure. J Pharmacol Exp Ther. 2019;371:642-651. PMID: 31601682

 

Ma A, Hong J, Shanks J, Rudebush T, Yu L, Hackfort BT, Wang H, Zucker IH, Gao L (2019). Upregulating Nrf2 in the RVLM ameliorates sympatho-excitation in mice with chronic heart failure. Free Radic Biol Med. 2019;141:84-92. PMID: 31181253

 

Wafi AM, Yu L, Gao L, Zucker IH (2019). Exercise training upregulates Nrf2 protein in the rostral ventrolateral medulla of mice with heart failure. J Appl Physiol (1985). 2019;127:1349-1359. PMID: 31556830

 

Shanks J, de Morais SDB, Gao L, Zucker IH, Wang HJ (2019). TRPV1 (Transient Receptor Potential Vanilloid 1) Cardiac Spinal Afferents Contribute to Hypertension in Spontaneous Hypertensive Rat.

Hypertension. 2019;74:910-920. PMID: 31422690

 

Wafi AM, Hong J, Rudebush TL, Yu L, Hackfort B, Wang H, Schultz HD, Zucker IH, Gao L (2019). Curcumin improves exercise performance of mice with coronary artery ligation-induced HFrEF: Nrf2 and antioxidant mechanisms in skeletal muscle. J Appl Physiol (1985). 2019;126:477-486.PMID: 30462567

Additional Publications in Pubmed. 

 

COLLABORATORS

 

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Chittibabu (Babu) Guda, PhD
Dept. of Genetics, Cell Biology & Anatomy, UNMC

Vikas Kumar, PhD
Dept. of Genetics, Cell Biology & Anatomy, UNMC
Mass Spectrometry and Proteomics Core 
Song-Young Park, PhD
School of Health and Kinesiology, UNO
 
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Dr. Hanjun Wang, MD
Dept. of Anesthesiology, UNMC
Dr. Irving H. Zucker, PhD
Dept. of Cellular & Integrative Physiology, UNMC