Valentin A. Pavlov, PhD

Valentin A. Pavlov, PhD is associate Investigator at the Feinstein Institute for Medical Research and associate professor at the Hofstra North Shore-LIJ School of Medicine. Dr Pavlov did his undergraduate work at the University of Sofia “St Kliment Ohridski” in Sofia, Bulgaria. He received his PhD in Physiology, Pathophysiology and Pharmacology from the same university in 1994, working on the metabolism of polyamines. Dr Pavlov was awarded a Royal Society and NATO postdoctoral fellowship in 1999, to work on the anticancer properties of novel polyamine analogues at the School of Life Sciences, The Robert Gordon University, Aberdeen, Scotland (UK).

In 2002 Dr Pavlov joined the research group of Dr Kevin Tracey at The Feinstein Institute for Medical Research and began his studies on the neural regulation of immune function and inflammation and the therapeutic implications of this regulation.

Dr Pavlov has published over 55 peer-reviewed papers and book chapters and has been a co-inventor of one patent and two patent applications. He has been an invited speaker at BioScience, Digestive Disease Week, FASEB Research Conference and other major scientific forums in the US, UK and Germany. Dr Pavlov is a member of European Association for Cancer Research, American Shock Society, Society for Neuroscience, and International Brain Research Organization. He has been a reviewer for a number of journals, including Nature Reviews Immunology, Nature Reviews Rheumatology, Proceedings of the National Academy of Sciences of the USA, The Journal of Immunology, Critical Care Medicine, American Journal of Physiology (Endocrinology and Metabolism), and Molecular Medicine. Dr Pavlov has also served as a grant reviewer for Biotechnology and Biological Sciences Research Council (UK), Association for International Cancer Research, The Broad Foundation, Dutch Digestive Foundation and Neurological Foundation of New Zealand.

Dr Pavlov’s research focuses on the role of the nervous system in the regulation of inflammation. Inflammation is a normal and important response to infection and injury. Inflammation is localized and temporary and upon its resolution, immune and physiological homeostasis is restored. However, disrupted immune regulation can result in excessive or chronic inflammation with deleterious consequences. This state underlies the pathogenesis of sepsis, rheumatoid arthritis, inflammatory bowel disease and other inflammatory and autoimmune disorders. Understanding endogenous mechanisms that regulate immune function and inflammation is critical for the development of novel therapeutic strategies to prevent or neutralize excessive inflammatory responses. Studies led by Kevin Tracey at the Feinstein Institute have revealed that bidirectional communication between the immune system and the brain is vital for controlling inflammation. The vagus nerve and peripheral, alpha7 nicotinic receptor-mediated signaling play an important role in this communication and are key components of a physiological mechanism – the cholinergic anti-inflammatory pathway.

Dr Pavlov’s research has led to the discovery that brain cholinergic mechanisms, mediated through muscarinic acetylcholine receptors play an important role in the neural control of immune function and inflammation. These brain mechanisms are functionally associated with the cholinergic anti-inflammatory pathway and can be activated by cholinergic compounds such as galantamine and other centrally-acting acetylcholinesterase inhibitors. Some of these compounds are FDA approved for the treatment of Alzheimer’s disease and have been used in the clinical management of myasthenia gravis. This is important because previous clinical experience and knowledge about the safety profile of these compounds would facilitate performing clinical studies in patients with inflammatory diseases.

Chronic inflammation as a result of immune and metabolic dysregulation is also a characteristic feature in patients with obesity and the metabolic syndrome. This chronic inflammatory state is causally linked with insulin resistance and the epidemic of type 2 diabetes mellitus and cardiovascular disease. Decreased vagus nerve activity in the context of obesity has been reported, which raises the intriguing possibility that dysregulation of vagus nerve-mediated anti-inflammatory signaling might contribute to the pathogenesis of obesity and its related comorbidities. Dr Pavlov’s work has recently revealed that the acetylcholinesterase inhibitor galantamine alleviates inflammation, insulin resistance and fatty liver disease in a preclinical model of diet-induced obesity. These findings complement other recent studies demonstrating that selective activation of the cholinergic anti-inflammatory pathway suppresses obesity-associated inflammation and reverses metabolic complications. We can now consider using cholinergic modalities with existing or new therapeutic approaches to target neural, endocrine and immune functions for therapeutic benefit in patients with obesity-related disorders.

Dr Pavlov’s current research also exploits possibilities of direct activation of brain neurocircuits to control inflammation in preclinical settings of inflammatory conditions. Other aspects of his research are related to exploring cholinergic modalities and vagus nerve anti-inflammatory signaling in preclinical settings of inflammatory bowel disease and cancer-associated immune dysfunction.

Collaboration is key in performing interdisciplinary research with the goal to translate research findings to treatments of diseases. Dr Pavlov has had the privilege to collaborate with Kevin Tracey and members of Tracey Lab, Yousef Al-Abed, Peter Davies, Betty Diamond, Christine Metz, Edmund Miller, Marc Symons, Kaie Ojamaa and many other fine scientists in and outside the Feinstein Institute.

Tea Tsaava, MD
Research Scientist
Email: ttsaava@nshs.edu
Phone: (516) 562-2312

Meghan Dancho, BSc
Research Assistant
Email: mdancho@nshs.edu
Phone: (516) 562-2313

Matthew Tanzi, BA
Research Assistant
Email: mtanzi@nshs.edu
Phone: (516) 562-2105

University of Sofia “St. Kliment Ohridski”, Sofia, Bulgaria
Degree: BSc
1985
Field of Study: Molecular Biology

University of Sofia “St. Kliment Ohridski”, Sofia, Bulgaria
Degree: MSc
1987
Field of Study: Physiology

University of Sofia “St. Kliment Ohridski”, Sofia, Bulgaria
Degree: PhD
1994
Field of Study: Physiology, Pathophysiology and Pharmacology

School of Life Sciences (formerly School of Applied Sciences), The Robert Gordon University, Aberdeen, Scotland (UK)
Degree: Postdoctoral Fellow
2000
Field of Study: Molecular Biology and Cancer Research

1993 Israel-Bulgaria Education and Research Exchange Program Research Scholarship Award
1995 Bulgarian Ministry of Education Science and Technology Young Investigator Research Grant Award
1999 Royal Society and NATO Postdoctoral Fellowship Award
2005 North Shore-LIJ Institute for Medical Research Competitive Faculty Award

1. Pavlov VA and Tracey KJ (2012) “The vagus nerve and the inflammatory reflex-linking immunity and metabolism.” Nat Rev Endo 8(12):743-54.
2. Rosas-Ballina M, Olofsson PS, Ochani M, Valdés-Ferrer SI, Levine YA, Reardon C, Tusche MW, Pavlov VA, Andersson U, Chavan S, Mak TW, Tracey KJ.(2011) “Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit.” Science, 334(6052):98-101.
3. Satapathy SK, Ochani M, Dancho M, Hudson LK, Rosas-Ballina M, Valdes-Ferrer SI, Olofsson PS, Harris YT, Roth J, Chavan S, Tracey KJ, Pavlov VA  (2011) “Galantamine alleviates inflammation and other obesity-associated complications in high-fat diet-fed mice.” Mol Med, 17(7-8):599-606.
4. Al-Abed Y, Metz CN, Cheng KF, Aljabari B, Vanpatten S, Blau S, Lee H, Ochani M, Pavlov VA, Coleman T, Meurice N, Tracey KJ, Miller EJ. (2011) “Thyroxine is a potential endogenous antagonist of macrophage migration inhibitory factor (MIF) activity.” Proc Natl Acad Sci USA, 108(20):8224-7.
5.  Norman GJ, Morris JS, Karelina K, Weil ZM, Zhang N, Al-Abed Y, Brothers HM, Wenk GL, Pavlov VA, Tracey KJ, Devries AC.  (2011) “Cardiopulmonary arrest and resuscitation disrupts cholinergic anti-inflammatory processes: a role for cholinergic alpha7 nicotinic receptors.” J Neurosci, 31(9):3446-52.
6. Pavlov VA, Ulloa L, and Metz CN,  ”Infection and Sepsis, In: The brain and host defense.“ Neuroimmune Biology, vol.9, Ed. Arnason, BG., 2010, pp. 309-321, Elsevier, ISBN 978-0-444-53544-3 
7. Pavlov VA, Parrish WR, Rosas-Ballina M, Ochani M, Ochani K, Puerta M, Chavan S, Al-Abed Y, Tracey KJ (2009) “Brain acetylcholinesterase activity regulates systemic cytokine levels through the cholinergic anti-inflammatory pathway.” Brain Behav Immun, 23: 41-45.
8. Parrish WR, Rosas-Ballina M, Puerta M, Ochani M, Ochani K, Hudson LQ, Johnson S, Czura C, Miller E, Al-Abed, Y, Tracey KJ, and Pavlov VA (2008) “Modulation of TNF release by choline requires alpha7 nicotinic subunit acetylcholine receptor signaling.” Mol Med, 14(9-10), 567-574.
9. Pavlov VA, Ochani M, Yang L, Gallowitsch-Puerta M, Ochani K, Lin X, Levi J, Parrish W, Rosas-Ballina, M, Czura, CJ, LaRosa GJ,   Miller EJ, Tracey KJ, Al-Abed Y. (2007) “Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis” Crit Care Med, 35(4), 1139-44.
10. Pavlov VA, Ochani M, Gallowistch-Puerta M, Ochani K, Huston J, Czura CJ, Al-Abed Y and Tracey KJ (2006) “Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia.” Proc Nat Acad Sci USA, 103(13), 5219-23.

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