Srinivas Sriramula, BVSC, MVSC, PhD

Education/Employment

2023 – present Associate Professor (Tenured), East Carolina University, Greenville, NC
2017 – 2023 Assistant Professor (Tenure-track), East Carolina University, Greenville, NC
2015 – 2017 Instructor (Research), Louisiana State University Health Sciences Center, New Orleans, LA
2011- 2015 Postdoctoral Fellow, Louisiana State University Health Sciences Center, New Orleans, LA
2010 Ph.D., School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA.
2004 Master of Veterinary Science (MVSc), ANGR Agricultural University, Hyderabad, India.
2001 Bachelor of Veterinary Science and Animal Husbandry (BVSc&AH), ANGR Agricultural University, Hyderabad, India.

Research Interests

The overarching goal of my research is to understand the bidirectional communication between the central nervous system and the immune system in regulation of cardiovascular and neurodegenerative diseases. The major focus of the lab is on investigating the role of kinin B1 receptor mediated inflammatory pathways and signaling mechanisms in the development of neurogenic hypertension. My laboratory uses an integrated physiological, pharmacological, molecular and gene-targeting approach, employing in vivo animal models of human diseases, complemented by in vitro primary cell cultures and cell lines. Some of the techniques used in our lab include blood pressure and heart rate recordings in conscious free moving mice using telemetry system, autonomic function assessment, brain nuclei-targeted microinjections, electron/fluorescence microscopy, and routine cell and molecular biology techniques. The major goal of my laboratory research is to elucidate mechanisms underlying the pathophysiology and identify novel potential therapeutic targets for the treatment of cardiovascular and neurodegenerative diseases.

Cardiovascular Parameters, Target Organs, Primary Cells and Immunoflorescence Staining

Current Research Projects:

Neuroimmune Mechanisms of Kinin B1 Receptor in Hypertension: This NIH/NHLBI R01 supported project is focused on investigating the role of kinin B1 receptor mediated neuroinflammation, oxidative stress, and sympathoexcitation in hypertension.

Kinin B1 receptor and target organ damage: This project is focused on identifying the role of kinin B1 receptor mediated target organ damage in cardiovascular diseases including hypertension, heart failure, and metabolic diseases. We are also investigating the interaction of Kallikrein Kinin System with Renin Angiotensin System in the pathogenesis of hypertension and associated organ damage.

Neuroinflammation in neurodegenerative disorders: In this project, in collaboration with other investigators at ECU, we are focused on using SARS-CoV-2 infection in a mouse model to investigate the long-term consequences of COVID-19 on inflammation, cognition, and neuropsychiatric symptoms and the possibility of increased risk of developing neurodegenerative diseases such as Parkinson’s and/or Alzheimer’s disease.

Selected Publications

For a full list of publications on PubMed click here.

ORCID: https://orcid.org/0000-0001-9937-1589

Mohammed M, Ogunlade B, Elgazzaz M, Berdasco C, Lakkappa N, Ghita I, Guidry J, Sriramula S, Xu J, Restivo L, Mendiola Pla M, Bowles D, Beyer A, Yue X, Lazartigues E, Filipeanu CM. Nedd4-2 upregulation is associated with ACE2 ubiquitination in hypertension. Cardiovascular Research. 2023. doi: 10.1093/cvr/cvad070. PMID: 37161607.
Theobald D, Nair AR, Sriramula S*, Francis J. Cardiomyocyte-specific Deletion of TLR4 Attenuates Angiotensin II-induced Hypertension and Cardiac Remodeling. Frontiers in Cardiovascular Medicine. 2023; 10:1074700. doi: 10.3389/fcvm.2023.1074700.
Theobald D, Sriramula S*. Kinin B1 Receptor Mediates Bidirectional Interaction between Neuroinflammation and Oxidative Stress. Antioxidants. 2023; 12, 150. doi: 10.3390/antiox12010150. PMID:
Byrne SE, Vishwakarma N, Sriramula S, Katwa LC. Dopamine receptor 3: A mystery at the heart of cardiac fibrosis. Life Sciences. 27:120918. PMID: 36041503.
Smeyne RJ, Eells JB, Chatterjee D, Byrne M, Akula SM, Sriramula S, O’Rourke DP, Schmidt P. COVID-19 Infection Enhances Susceptibility to Oxidative Stress-Induced Parkinsonism. Movement Disorders. 2022. doi: 10.1002/mds.29116. PMID: 35579496.
White A, Parekh RU, Theobald D, Pakala P, Myers AL, Van Dross R, Sriramula S. Kinin B1R Activation Induces Endoplasmic Reticulum Stress in Primary Hypothalamic Neurons. Frontiers in Pharmacology. 2022. 13:841068. doi: 10.3389/fphar.2022.841068. PMID: 35350763.
Basuli D, Parekh RU, White A, Thayyil A, Sriramula S. Kinin B1 Receptor Mediates Renal Injury and Remodeling in Hypertension. Frontiers in Medicine. 2022; 8:780834. PMID: 35118089.
Parekh RU, White A, Leffler KE, Biancardi VC, Eells JB, Abdel-Rahman AA, Sriramula S. Hypothalamic kinin B1 receptor mediates orexin system hyperactivity in neurogenic hypertension. Scientific Reports. 2021. 11:21050. PMID: 34702886.
Kissling A, Byrne S, Parekh RU, Melit-Thomas D, de Castro Brás LE, Lust RM, Clemens S, Sriramula S, Katwa LC. Loss of function in dopamine D3 receptor attenuates left ventricular cardiac fibroblasts migration and proliferation in vitro. Frontiers in Cardiovascular Medicine. 2021. 8:732282. PMID: 34708087.
Parekh RU, Sriramula S. Activation of Kinin B1R Upregulates ADAM17 and Results in ACE2 Shedding in Neurons. International Journal of Molecular Sciences. 22:145. PMID: 33375653
Sriramula S. Kinin B1 receptor: A target for neuroinflammation in hypertension. Pharmacological Research. 2020. 155:104715. PMID: 32087235.
Parekh RU, Robidoux J, Sriramula S. Kinin B1 Receptor Blockade Prevents Angiotensin II-induced Neuroinflammation and Oxidative Stress in Primary Hypothalamic Neurons. Cellular and Molecular Neurobiology. 2019. 40(5):845-857. PMID: 31865500.
Reed JT, Pareek T, Sriramula S, Pabbidi MR. Aging influences cerebrovascular myogenic reactivity and BK channel function in a sex-specific manner. Cardiovascular Research. 2019. 116:1372-1385. PMID: 31738403.
Basting T, Xu J, Mukerjee S, Epling J, Fuchs R, Sriramula S, Lazartigues E. Glutamatergic neurons of the paraventricular nucleus are critical contributors to the development of neurogenic hypertension. Journal of Physiology. 596:6235-6248. PMID: 30151830.
Xu J, Sriramula S, Lazartigues E. Excessive glutamate stimulation impairs ACE2 activity through ADAM17-mediated shedding in cultured cortical neurons. Cellular and Molecular Neurobiology. 2018, 38:1235-1243. PMID: 29766392.
Sriramula S*, Lazartigues E. Kinin B1 receptor promotes neurogenic hypertension through activation of centrally mediated mechanisms. 2017. 70:1122-1131. PMID: 29038201.
Xu J, Sriramula S, Xia H, Moreno-Walton L, Culicchia F, Domenig O, Poglitsch M, Lazartigues E. Clinical relevance and role of neuronal AT1 receptors in ADAM17-mediated ACE2 shedding in neurogenic hypertension. Circulation Research. 121:43-55.
Sriramula S*, Joseph Francis*. Tumor necrosis factor – alpha is essential for angiotensin II-induced ventricular remodeling: Role for oxidative stress. PLoS ONE. 2015. 10(9):e0138372.
Sriramula S, Xia H, Xu P, Lazartigues E. Brain-targeted angiotensin-converting enzyme 2 overexpression attenuates neurogenic hypertension by inhibiting cyclooxygenase-mediated inflammation. Hypertension. 2015. 65(3):577-86.
Xia H*, Sriramula S*, Kavaljit H, Lazartigues E. Brain ACE2 shedding contributes to the development of neurogenic hypertension. Circulation Research. 2013. 113:1087-1096.
Sriramula S, Cardinale JP, Francis J. Inhibition of TNF in the brain reverses alterations in RAS components and attenuates angiotensin II-induced hypertension. PLoS ONE. 2013. 8(5):e63847.
Sriramula S, Cardinale JP, Lazartigues E, Francis J. ACE2 overexpression in the paraventricular nucleus attenuates angiotensin Ii-induced hypertension. Cardiovascular Research 2011. 92:401-8. (Editorial Comment by Olaf Grisk, Cardiovascular Research. 2011, 92:365-366).
Sriramula S, Haque M, Majid DS, Francis J. Involvement of Tumor Necrosis Factor-alpha in Angiotensin II-Mediated Effects on Salt Appetite, Hypertension, and Cardiac Hypertrophy. 2008. 51(5):1345-1351.

Honors and Awards

2023 APS CNS Section Research Recognition Award from the American Physiology Summit (Drew Theobald)
2023 Martin Frank Diversity Travel Award from the American Physiology Summit (Acacia White)
2022 Cardiovascular Section Steven M. Horvath Professional Opportunity Award (to Graduate Student Acacia White)
2021 Outstanding Research Scholar, Brody School of Medicine at East Carolina University
2020 Hypertension 2020 Scientific Sessions Top Trainee Advocacy Award (to Graduate Student – Rohan Parekh)
2019 American Society of Nephrology/American Physiological Society Travel Award (to Fellow – Dr. Debargha Basuli)
2015 American Physiological Society Caroline tum Suden/Francis A. Hellebrandt Professional Opportunity Award
2014 American Physiological Society Cardiovascular Section Research Recognition Award
2013 Neural Control and Autonomic Regulation Section Postdoctoral and Early Career Research Recognition Award from American Physiological Society
2012 High Blood Pressure Research Conference New Investigator Travel Award for Trainees
2012 American Physiological Society Central Nervous System Research Recognition Award
2011 Annual High Blood Pressure Research Conference New Investigator Award

Grant Funding

NIH/NHLBI 1 RO1 HL153115-01 08/15/2020-07/31/2025
Role: PI; Project Title: Neuroimmune Mechanisms of Kinin B1 Receptor in Hypertension

Brody Brothers Endowment Award, ECU 01/01/2023 – 12/30/2023Role: Co-PI; Project Title: A Kinin B1R Antagonist as a Therapeutic to Prevent COVID-19 Pathology

American Parkinson Disease Association, 09/01/2023 – 8/31/2024Role: Co-I; Project Title: Mechanisms of SARS-CoV-2 infection induced dopamine neuron damage

Completed – American Heart Association Scientist Development Grant (15SDG25720021) 07/01/2015-06/30/2019 Role: PI; Project Title: Role of bradykinin B1 receptor in neurogenic hypertension

Laboratory Members

Name	Title	Building/Room	Phone
Robin Alligood	Research Specialist	BSOM 6W-35	252-744-1385
Dr. Ramesh Gogulothu	Postdoctoral Fellow	BSOM 6W-35	252-744-1385
Acacia White	Graduate Student	BSOM 6W-35	252-744-1385
Drew Theobald	Graduate Student	BSOM 6W-35	252-744-1385
Former Lab Members: Rohan Parekh (PhD student, 2018-2022) Drew Theobald (MS student, 2021-2023)