Anatoliy Gashev, M.D., Ph.D., D.MSci.
Associate Professor
Systems Biology and Translational Medicine
702 Southwest H.K. Dodgen Loop
Temple,
Texas 76504
Phone: 254-742-7147
Fax: 254-742-7145
Email: gashev@tamu.edu
Curriculum Vitae
(PDF)
Education and Post-Graduate Training
M.D., Therapy, General Practice, State Medical Academy, St. Petersburg, Russia, 1986
Ph.D., Physiology, Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia, 1989
Doctor of Medical Science, Physiology, Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia, 2000
Research Interests
The lymphatic system plays an important roles in the human body to maintain fluid and macromolecular balances and to remove products of metabolic exchange from the tissues. This system also is tightly involved in immune reactions. All of these important body functions require the existence of an effective lymph transport. The investigations of the last three decades provided us some information on how lymph moves but even until now we do not have a generally accepted detailed concept of the mechanisms of lymph transport and its regulation. The current paradox is that currently physicians undertake their attempts to correct lymphatic dysfunctions in humans in a situation with regulatory mechanisms responsible for normal lymph flow remaining unclear.
My scientific interests focus on the further understanding of all forces which move lymph centripetally, the sequence of the events during the lymphatic contractile cycle, the mechanisms of modulation of lymph flow by main factors of lymph dynamics such as transmural pressure and flow. Other directions of my scientific interests are influences of physical, neural and humoral factors on lymph flow, contractile coordination in lymphangion chains. Another recent research development in my lab is the project on investigation of the mechanisms of age-related alteration in lymph transport. Although all body systems are affected by aging, the effects of aging on the lymphatic transport component of any of these body functions are unknown.
Particularly, very little is known about the age-related alterations of phasic contractions of the lymphatic vessels, which are critical to the generation of lymph flow. Transporting lymphatic vessels work in a "self-regulatory mode" when their contractility constantly adjusts to the local fluid loads through pressure and flow dependent regulatory mechanisms. The central hypothesis of this work is that aging impairs both pressure and flow-dependent regulatory mechanisms in lymphatic vessels. This will result in a regression of the functional adaptive reserves in lymphatic contractility due to eNOS/iNOS imbalances, along with alterations in crossbridge activation mechanisms in lymphatic vessels. Such age-related changes in lymph transport system could diminish the ability of lymphatic vessels to provide adequate lymph transport component for many body functions.
The specific aims of this project are: 1) To determine the age-related changes in the sensitivity of lymphatic vessels to transmural pressure and to evaluate their adaptive contractile reserves. 2) To determine the age-related changes in the active mechanical properties of the lymphatic vessels. 3) To determine the age-related changes in the mechanisms of flow/NO-dependent regulation of lymphatic contractions. 4) To investigate the molecular mechanisms of age-related alterations in the regulation of lymphatic contractility and to develop an experimental model to improve the pump function of aged lymphatic vessels using the genetic/transfections and pharmacological tools.
The results of this research will provide the missing link between the age-related processes in the different tissues and the age-related differential changes in the ability of lymphatic vessels to provide the adequate transport of lymph from them in elderly organisms. The results of these studies will also provide the basic knowledge for the ways to improve lymphatic transport that is compromised during aging. The proposed experimental model approach may potentially open up new directions in the development of protective measures to improve the compromised pump function in aged lymphatic vessels.
Selected Publications
A.A. Gashev, M.J. Davis, O.Yu. Gasheva, Z.V. Nepiushchikh, W. Wang, P. Dougherty, K.A. Kelly, S. Cai, P.-Y. von der Weid, M. Muthuchamy, C.J. Meininger, D.C. Zawieja. Methods for Lymphatic Vessel Culture and Gene Transfection. Microcirculation, 2009, accepted June 16.
Wang W, Nepiyushchikh Z, Zawieja DC Phd, Chakraborty S, Zawieja SD, Gashev AA, Davis MJ, Muthuchamy M. Inhibition of myosin light chain phosphorylation decreases rat mesenteric lymphatic contractile activity.Am J Physiol Heart Circ Physiol. 2009 Jun 12. [Epub ahead of print] PMID: 19525378
Davis MJ, Davis AM, Ku CW, Gashev AA. Myogenic constriction and dilation of isolated lymphatic vessels. Am J Physiol Heart Circ Physiol. 2009 Feb;296(2):H293-302. Epub 2008 Nov 21. PMID: 19028793
Davis MJ, Davis AM, Lane MM, Ku CW, Gashev AA. Rate-sensitive contractile responses of lymphatic vessels to circumferential stretch. J Physiol. 2009 Jan 15;587(Pt 1):165-82. Epub 2008 Nov 10. PMID: 19001046
Petrenko VM, Gashev AA. Observations on the prenatal development of human lymphatic vessels with focus on basic structural elements of lymph flow. Lymphat Res Biol. 2008;6(2):89-95. Review. PMID: 18564924
P. Davis MJ, Lane MM, Davis AM, Durtschi D, Zawieja DC, Muthuchamy M, Gashev AA. Modulation of lymphatic muscle contractility by the neuropeptide substance. Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H587-97. Epub 2008 Jun 6. PMID: 18539752
Gashev AA, Ann N Y. Lymphatic vessels: pressure- and flow-dependent regulatory reactions. Acad Sci. 2008;1131:100-9. Review. PMID: 18519963
Behnke BJ, Zawieja DC, Gashev AA, Ray CA, Delp MD. Diminished mesenteric vaso- and venoconstriction and elevated plasma ANP and BNP with simulated microgravity. J Appl Physiol. 2008 May;104(5):1273-80. Epub 2008 Jan 24. PMID: 18218919
Gashev AA, Wang W, Laine GA, Stewart RH, Zawieja DC. Characteristics of the active lymph pump in bovine prenodal mesenteric lymphatics. Lymphat Res Biol. 2007;5(2):71-9. PMID: 17935475
Gasheva OY, Knippa K, Nepiushchikh ZV, Muthuchamy M, Gashev AA. Age-Related Alterations of Active Pumping Mechanisms in Rat Thoracic Duct. Microcirculation. 2007 Oct 8;:1-13 [Epub ahead of print] PMID: 17924280
Gashev AA, Wang W, Laine GA, Stewart RH, Zawieja DC. Characteristics of the active lymph pump in bovine prenodal mesenteric lymphatics. Lymphat Res Biol. 2007;5(2):71-9. PMID: 17935475
Zhang R, Gashev AA, Zawieja DC, Lane MM, Davis MJ. Length-dependence of lymphatic phasic contractile activity under isometric and isobaric conditions. Microcirculation. 2007 Aug;14(6):613-25. PMID: 17710632
Davis MJ, Lane MM, Scallan JP, Gashev AA, Zawieja DC. An automated method to control preload by compensation for stress relaxation in spontaneously contracting, isometric rat mesenteric lymphatics. Microcirculation. 2007 Aug;14(6):603-12. PMID: 17710631
Zhang RZ, Gashev AA, Zawieja DC, Davis MJ. Length-tension relationships of small arteries, veins, and lymphatics from the rat mesenteric microcirculation. Am J Physiol Heart Circ Physiol. 2007 Apr; 292(4):H1943-52. Epub 2006 Dec 15. PMID: 17172274
Dixon JB, Gashev AA, Zawieja DC, Moore JE Jr, Coté GL. Image correlation algorithm for measuring lymphocyte velocity and diameter changes in contracting microlymphatics. Ann Biomed Eng. 2007 Mar;35(3):387-96. Epub 2006 Dec 7. PMID: 17151922
Quick CM, Venugopal AM, Gashev AA, Zawieja DC, Stewart RH. Intrinsic pump-conduit behavior of lymphangions. Am J Physiol Regul Integr Comp Physiol. 2007 Apr;292(4):R1510-8. Epub 2006 Nov 22. PMID: 17122333
Dixon JB, Greiner ST, Gashev AA, Cote GL, Moore JE, Zawieja DC. Lymph flow, shear stress, and lymphocyte velocity in rat mesenteric prenodal lymphatics. Microcirculation. 2006 Oct-Nov;13(7):597-610. PMID: 16990218
Gasheva OY, Zawieja DC, Gashev AA. Contraction-initiated NO-dependent lymphatic relaxation: a self-regulatory mechanism in rat thoracic duct. J Physiol. 2006 Sep 15;575(Pt 3):821-32. Epub 2006 Jun 29. PMID: 16809357
Davis MJ, Zawieja DC, Gashev AA. Automated measurement of diameter and contraction waves of cannulated lymphatic microvessels. Lymphat Res Biol. 2006 Spring;4(1):3-10. PMID: 16569200
Dixon JB, Zawieja DC, Gashev AA, Coté GL. Measuring microlymphatic flow using fast video microscopy. J Biomed Opt. 2005 Nov-Dec;10(6):064016. PMID: 16409081
Gashev AA, Delp MD, Zawieja DC. Inhibition of active lymph pump by simulated microgravity in rats. Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2295-308. Epub 2006 Jan 6. PMID: 16399874
Gashev AA, Davis MJ, Delp MD, Zawieja DC. Regional variations of contractile activity in isolated rat lymphatics. Microcirculation. 2004 Sep;11(6):477-92. PMID: 15371129
Muthuchamy M, Gashev A, Boswell N, Dawson N, Zawieja D. Molecular and functional analyses of the contractile apparatus in lymphatic muscle. FASEB J. 2003 May;17(8):920-2. Epub 2003 Mar 28. PMID: 12670880
Gashev AA. Physiologic aspects of lymphatic contractile function: current perspectives. Ann N Y Acad Sci. 2002 Dec;979:178-87; discussion 188-96. Review. PMID: 12543727
Gashev AA, Davis MJ, Zawieja DC. Inhibition of the active lymph pump by flow in rat mesenteric lymphatics and thoracic duct. J Physiol. 2002 May 1;540(Pt 3):1023-37. PMID: 11986387
Gashev AA, Zawieja DC. Physiology of human lymphatic contractility: a historical perspective. Lymphology. 2001 Sep;34(3):124-34. PMID: 11549124
Gashev AA, Orlov RS, Zawieja DC. [Contractions of the lymphangion under low filling conditions and the absence of stretching stimuli. The possibility of the sucking effect] Ross Fiziol Zh Im I M Sechenova. 2001 Jan;87(1):97-109. Russian. PMID: 11227869
Gashev AA. [The mechanism of the formation of a reverse fluid filling in the lymphangions] Fiziol Zh SSSR Im I M Sechenova. 1991 Jul;77(7):63-9. Russian. PMID: 1668160
Gashev AA. [The pump function of the lymphangion and the effect on it of different hydrostatic conditions] Fiziol Zh SSSR Im I M Sechenova. 1989 Dec;75(12):1737-43. Russian. PMID: 2628032
Gashev AA. [Pumping function of lymphangion depending on various hydrostatic gradients] Dokl Akad Nauk SSSR. 1989;308(5):1261-4. Russian. PMID: 2612352.
