ANNA N. BUKIYA, Ph.D.

Associate Professor
Pharmacology

Office: 230K TRANSLATIONAL RESEARCH BUILDING
71 SOUTH MANASSAS
MEMPHIS TN 38163
Tel: (901) 448-2128
abukiya@uthsc.edu

Research Interest/Specialty

The major line of interest in the lab is the lipid regulation of alcohol effect on cerebral circulation at different points during lifetime (from in utero into late adulthood). We are currently pursuing several lines. We are studying the role of dietary cholesterol in the physiology and pathology of cerebral arteries via ion channel involvement. Using rat model of high-cholesterol diet, we were the first to show that dietary cholesterol was a critical nutritional regulator of alcohol-induced constriction of cerebral arteries. Moreover, widely used statin therapy enhances alcohol-induced constriction when compared to hyperlipidemic state. After establishing the phenomenon of cholesterol control over alcohol effect at organ level, we are currently dissecting out molecular mechanisms that enable cholesterol regulation of alcohol-induced constriction of cerebral arteries.

Another line of work is focused on the fetal cerebral circulation as a target of maternal alcohol drinking. Using baboon model of pregnancy, we demonstrated that maternal binge drinking episodes reduced velocity of blood flow in fetal cerebral arteries. Remarkably, drops in blood flow velocity preceded growth restriction characteristic of alcohol-exposed fetuses. Using in vitro pressurized fetal cerebral arteries, we discovered that ethanol at physiologically relevant levels dilated fetal cerebral arteries, the dilation was blocked in presence of cannabinoid receptor antagonists. We are currently aiming at identification of novel targets of maternal drinking in fetal cerebral arteries. This work may lay a foundation for early diagnostics and successful prevention/treatment of the fetal alcohol spectrum disorders (FASD) and fetal alcohol syndrome (FAS) that are estimated to affect at least 1% of births in the USA.

Novel line of work in the lab is focusing on the consequences of alcohol and cannabinoid consumption of the function of cerebral arteries. In addition, we are working on the interaction of inwardly rectifying potassium channels with physiologically relevant lipids: cholesterol, PIP2, and fatty acids. This line of work is carried out in collaboration with Dr. Rosenhouse-Dantsker (UIllinois).  

Curriculum Vitae

Research Keywords

Potassium channel, endocannabinoids, alcohol, cholesterol, fetal alcohol spectrum disorders, statin (atorvastatin), cerebral artery

Recent Reviews and Book chapters

Bukiya A., Rosenhouse-Dantsker A. “Hypercholesterolemia effect on potassium channels” in Hypercholesterolemia. (2015). S.A. Kumar, ed. INTECH, pp. 95-119

Dopico A., Bukiya A., G. Kuntamallappanavar. “Membrane lipids and modulation of vascular smooth muscle ion channels” in Vascular ion channels in physiology and disease. (2016). I. Levitan and A. Dopico, eds. Springer, pp. 349-380. 

Bukiya A., Dopico A. “Cholesterol and caffeine modulate alcohol actions on cerebral arteries and brain” in Addictive substances and neurological disease. (2017). R.R. Watson and S. Zibadi, eds. Elsevier, pp. 355-364.

Dopico AM, Bukiya AN, Bettinger JC. “Voltage-Sensitive Potassium Channels of the BK Type and Their Coding Genes Are Alcohol Targets in Neurons” in Handbook of Experimental Pharmacology. (2017). Springer, Berlin, Heidelberg, pp. 1-29. 

Dopico, A.M., Bukiya, A.N., Kuntamallappanavar, G., Liu, J. (2016) Modulation of BK Channels by Ethanol. Int Rev Neurobiol. 128:239-279. 

Bukiya, A.N., Dopico, A.M. (2017) Common structural features of cholesterol binding sites in crystallized soluble proteins. J Lipid Res. 58(6):1044-1054.

Dopico AM, Bukiya AN. (2017) Regulation of Ca2+-Sensitive K+ Channels by Cholesterol and Bile Acids via Distinct Channel Subunits and Sites. Curr Top Membr. 80:53-93. 

Bukiya AN, Dopico AM. (2018) Fetal cerebral circulation as target of maternal alcohol consumption. Alcohol Clin Exp Res. 42(6):1006-1018. 

Dopico A, Bukiya A, Jaggar J. (2018) Calcium- and voltage-gated BK channels in vascular smooth muscle. Pflugers Arch. In press. 

Publications

  1. Tobiasz, AM, Duncan, JR, Bursac, Z, Sullivan, RD, Tate, DL, Dopico, AM, Bukiya, AN, Mari, G. The Effect of Prenatal Alcohol Exposure on Fetal Growth and Cardiovascular Parameters in a Baboon Model of Pregnancy. Reprod Sci, 25 (7), 1116-1123, 2018.
  2. Bukiya, AN, Seleverstov, O, Bisen, S, Dopico, AM. Age-Dependent Susceptibility to Alcohol-Induced Cerebral Artery Constriction. J Drug Alcohol Res, 5, 2018.
  3. Kuntamallappanavar, G, Bisen, S, Bukiya, AN, Dopico, AM. Differential distribution and functional impact of BK channel beta1 subunits across mesenteric, coronary, and different cerebral arteries of the rat. Pflugers Arch, 469 (2), 263-277, 2017.
  4. Chang, J, Fedinec, AL, Kuntamallappanavar, G, Leffler, CW, Bukiya, AN, Dopico, AM. Endothelial Nitric Oxide Mediates Caffeine Antagonism of Alcohol-Induced Cerebral Artery Constriction. J Pharmacol Exp Ther, 356 (1), 106-15, 2016.
  5. Bukiya, AN, Osborn, CV, Kuntamallappanavar, G, Toth, PT, Baki, L, Kowalsky, G, Oh, MJ, Dopico, AM, Levitan, I, Rosenhouse-Dantsker, A. Cholesterol increases the open probability of cardiac KACh currents. Biochim Biophys Acta, 1848 (10 Pt A), 2406-13, 2015.
  6. Bukiya, AN, McMillan, J, Liu, J, Shivakumar, B, Parrill, AL, Dopico, AM. Activation of calcium- and voltage-gated potassium channels of large conductance by leukotriene B4. J Biol Chem, 289 (51), 35314-25, 2014.
  7. McMillan, JE, Bukiya, AN, Terrell, CL, Patil, SA, Miller, DD, Dopico, AM, Parrill, AL. Multi-generational pharmacophore modeling for ligands to the cholane steroid-recognition site in the β₁ modulatory subunit of the BKCa channel. J Mol Graph Model, 54, 174-83, 2014.
  8. Bukiya, AN, McMillan, JE, Fedinec, AL, Patil, SA, Miller, DD, Leffler, CW, Parrill, AL, Dopico, AM. Cerebrovascular dilation via selective targeting of the cholane steroid-recognition site in the BK channel β1-subunit by a novel nonsteroidal agent. Mol Pharmacol, 83 (5), 1030-44, 2013.
  9. Bukiya, AN, Patil, SA, Li, W, Miller, DD, Dopico, AM. Calcium- and voltage-gated potassium (BK) channel activators in the 5β-cholanic acid-3α-ol analogue series with modifications in the lateral chain. ChemMedChem, 7 (10), 1784-92, 2012.
  10. Singh, AK, McMillan, J, Bukiya, AN, Burton, B, Parrill, AL, Dopico, AM. Multiple cholesterol recognition/interaction amino acid consensus (CRAC) motifs in cytosolic C tail of Slo1 subunit determine cholesterol sensitivity of Ca2+- and voltage-gated K+ (BK) channels. J Biol Chem, 287 (24), 20509-21, 2012.
  11. Deng, W, Bukiya, AN, Rodríguez-Menchaca, AA, Zhang, Z, Baumgarten, CM, Logothetis, DE, Levitan, I, Rosenhouse-Dantsker, A. Hypercholesterolemia induces up-regulation of KACh cardiac currents via a mechanism independent of phosphatidylinositol 4,5-bisphosphate and Gβγ. J Biol Chem, 287 (7), 4925-35, 2012.
  12. Bukiya, AN, Singh, AK, Parrill, AL, Dopico, AM. The steroid interaction site in transmembrane domain 2 of the large conductance, voltage- and calcium-gated potassium (BK) channel accessory β1 subunit. Proc Natl Acad Sci U S A, 108 (50), 20207-12, 2011.
  13. Bukiya, AN, Vaithianathan, T, Kuntamallappanavar, G, Asuncion-Chin, M, Dopico, AM. Smooth muscle cholesterol enables BK β1 subunit-mediated channel inhibition and subsequent vasoconstriction evoked by alcohol. Arterioscler Thromb Vasc Biol, 31 (11), 2410-23, 2011.
  14. Bukiya, AN, Belani, JD, Rychnovsky, S, Dopico, AM. Specificity of cholesterol and analogs to modulate BK channels points to direct sterol-channel protein interactions. J Gen Physiol, 137 (1), 93-110, 2011.
  15. Bukiya, AN, McMillan, J, Parrill, AL, Dopico, AM. Structural determinants of monohydroxylated bile acids to activate beta 1 subunit-containing BK channels. J Lipid Res, 49 (11), 2441-51, 2008.
  16. Vaithianathan, T, Bukiya, A, Liu, J, Liu, P, Asuncion-Chin, M, Fan, Z, Dopico, A. Direct regulation of BK channels by phosphatidylinositol 4,5-bisphosphate as a novel signaling pathway. J Gen Physiol, 132 (1), 13-28, 2008.
  17. Patil, S, Bukiya, AN, Li, W, Dopico, AM, Miller, D. Design and synthesis of hydroxy-alkynoic acids and their methyl esters as novel activators of BK channels. Bioorg Med Chem Lett, 18 (11), 3427-30, 2008.
  18. Bukiya, AN, Vaithianathan, T, Toro, L, Dopico, AM. The second transmembrane domain of the large conductance, voltage- and calcium-gated potassium channel beta(1) subunit is a lithocholate sensor. FEBS Lett, 582 (5), 673-8, 2008.
  19. Bukiya, AN, Liu, J, Toro, L, Dopico, AM. Beta1 (KCNMB1) subunits mediate lithocholate activation of large-conductance Ca2+-activated K+ channels and dilation in small, resistance-size arteries. Mol Pharmacol, 72 (2), 359-69, 2007.