PHD, Physiology & Biophysics, University of Southern California, 1991
B.S. (Honors), Biology, Chinese University of Hong Kong, 1984
Interdisciplinary and Emerging Signature Programs
Allergy, Immunology & Infectious Disease
Cancer Biology
Cardiovascular
Cellular and Molecular Biology
Environmental & amp; Global Health
Pulmonary Physiology
Research Interests
<P>The research interests of our laboratory are to develop and apply confocal fluorescence microscopy, laser-based video microscopy, and flash photolysis of caged compounds to study renal cellular function in situ and in vivo. Currently we are investigating the regulation of water channels (aquaporin-2) trafficking in kidney collecting duct by antidiuretic hormone (vasopressin), the role of integrins and Ca2+ microdomains in mechanical signal transduction in renal vascular smooth muscle, and cellular mechanisms of pressure natriuresis and its relationship with the development of hypertension.</P>
<P>In addition, we're studying the regulation of blood pressure and renal functions, with emphasis in developing novel imaging techniques for in vivo and in situ studies, and using interdisciplinary approaches to study the physiological phenomena from subcellular to organ level. There are two active projects in lab, which are supported by NIH and AHA.</P>
<P>1. Intracellular Ca2+ oscillations and trafficking of aquaporin-2 (AQP2) in intact inner medullary collecting duct cells. Confocal fluorescence microscopy allows the study of physiological process in a single cell in a perfused tubule without the complication of out-of-focus-fluorescence signal derived from the other cells. By combining confocal fluorescence microscopy and tubular microperfusion technique, we are the first to demonstrate that vasopressin (AVP) in physiological range ( 0.01 0.1 nM) mobilizes intracellular Ca2+ in form of oscillations in intact inner medullary collecting duct (J. Biol. Chem. 2000). By developing a novel confocal fluorescence imaging technique using a styryl dye (FM1-43) to monitor real time exocytosis of aquaporin-2 in inner medullary collecting duct (IMCD), we provide the first direct evidence that AVP induced AQP2 exocytotic insertion is Ca2+ dependent (J. Physiol. 2002). We also have evidence that AVP uses not only PKA but also EPAC as cAMP receptor to induce AQP2 apical exocytosis (Am. J. Physiol. 2005).</P>
<P>2. Integrin-mediated mechanotransduction in renal vascular smooth muscle cells. Myogenic response and tubuloglomerular feedback are the two major mechanisms responsible to provide renal blood flow autoregulation. But mechanism of mechanotransduction in myogenic response is not known. We hypothesize that increase of transmural pressure (stretch) alters the attachment between extracellular matrix (ECM) and integrins in vascular smooth muscle, and that mechanical force is transduced via integrin to trigger Ca2+ sparks (local subcellular Ca2+ release from ryanodine receptors, detected by high speed confocal microscopy) to initiate and maintain myogenic contraction. We are testing these hypotheses by applying controlled mechanical force using fibronectin-coated paramagnetic beads (or nanoparticles) and monitoring the occurrence of Ca2+ sparks in freshly isolated renal vascular smooth muscles, and examining the effects of transmural pressure in the frequency of Ca2+ sparks in intact renal vascular smooth muscle cells. (Am. J. Physiol 2007)</P>
Awards/Honors
National Kidney Foundation Young Investigator Grant (National Kidney Foundation - 1994)
Clifford and Evelyn Cherry Fellowship Award (American Heart Association - 1992)
American Heart Association Postdoctoral Fellowship (American Heart Association - 1992)
Memberships
Member (American Society of Nephrology, 2008 - Present)
Member (American Physiological Society, 2008 - Present)
Ednie A, R, W, Deng K, P, Yip E, S, Bennett. Reduced myocyte complex N-glycosylation causes dilated cardiomyopathyFASEB J. 33(1) , 2019.
Leung C, S, T, L, Yeung K, P, Yip K, K, Wong S, Y, Ho L, S, Mangala A, K, Sood G, Lopez-Berestein J, Sheng S, T, C, Wong M, J, Birrer and S, C, Mok. Cancer-associated fibroblasts regulated endothelial adhesion protein LPP to promote ovarian cancer chemoresistanceJ Clin. Invest. 128(2) : 589-606, 2018.
Yip K, P, L, Balasubramanian C, Kan L, Wang R, Liu L, Ribeiro-Silva J, S, K, Sham. Intraluminal Pressure Triggers Myogenic Response via Activation of Calcium Spark and Calcium-Activated Chloride Channel in Rat Renal Afferent ArterioleAm J Physiol Renal Physiol. 315: F1592-F1600, 2018.
Wang L, Song J, Buggs J, Wei J, Wang S, Zhang J, Zhang G, Lu Y, Yip KP, Liu R. A new mouse model of hemorrhagic shock-induced acute kidney injury.American journal of physiology. Renal physiology. 312(1) : F134-F142, 2017.
Lo CM, Lo JC, Sato PY, Yeung TL, Mok SC, Yip KP. Monitoring of ovarian cancer cell invasion in real time with frequency-dependent impedance measurement.American journal of physiology. Cell physiology. 311(6) : C1040-C1047, 2016.
Wang L, Shen C, Liu H, Wang S, Chen X, Roman RJ, Juncos LA, Lu Y, Wei J, Zhang J, Yip KP, Liu R. Shear stress blunts tubuloglomerular feedback partially mediated by primary cilia and nitric oxide at the macula densa.American journal of physiology. Regulatory, integrative and comparative physiology. 309(7) : R757-66, 2015.
Yeung TL, Leung CS, Yip KP, Au Yeung CL, Wong ST, Mok SC. Cellular and molecular processes in ovarian cancer metastasis. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis.American Journal of Physiology. Cell Physiology. 309(7) : C444-56, 2015.
Yip KP, Cha BJ, Tse CM, Amin ME, Amin J. Functional Expression of Aquaporin-2 Tagged with Photoconvertible Fluorescent Protein in mpkCCD Cells.Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, biochemistry, and pharmacology. 36(2) : 670-82, 2015.
Kan C, Yip KP, Yang H. Two-phase greedy pursuit algorithm for automatic detection and characterization of transient calcium signaling.IEEE Journal of Biomedical and Health Informatics. 19(2) : 687-97, 2015.
Yeung TL Leung CS Yip KP Au Yeung CL Wong STC and Mok SC. Cellular and molecular processes in ovarian cancer metastasis.Am. J. Physiol. Cell Physiol.. 309(7) : C444-56, 2015.
Leung CS, Yeung TL, Yip KP, Pradeep S, Balasubramanian L, Liu J, Wong KK, Mangala LS, Armaiz-Pena GN, Lopez-Berestein G, Sood AK, Birrer MJ, Mok SC. Calcium-dependent FAK/CREB/TNNC1 signalling mediates the effect of stromal MFAP5 on ovarian cancer metastatic potential.Nature Communications. 5: 5092, 2014.
Yip KP, Tse CM. Modulation of Na⁺/H⁺ exchanger 3 trafficking and activity in rat proximal tubule.Acta Physiologica (Oxford, England). 210(3) : 458-9, 2014.
Balasubramanian L, Lo CM, Sham JS, Yip KP. Remanent cell traction force in renal vascular smooth muscle cells induced by integrin-mediated mechanotransduction.American Journal of Physiology. Cell Physiology. 304(4) : C382-91, 2013.
Yip KP, Sham JS. Tracking stars: automated two-dimensional analysis of Ca²⁺ events. Focus on "Automated region of interest analysis of dynamic Ca²⁺ signals in image sequences".American Journal of Physiology. Cell Physiology. 303(3) : C233-5, 2012.
Yip KP, Sham JS. Mechanisms of vasopressin-induced intracellular Ca2+ oscillations in rat inner medullary collecting duct.American Journal of Physiology. Renal Physiology. 300(2) : F540-8, 2011.
Mok SC, Bonome T, Vathipadiekal V, Bell A, Johnson ME, Wong KK, Park DC, Hao K, Yip DK, Donninger H, Ozbun L, Samimi G, Brady J, Randonovich M, Pise-Masison CA, Barrett JC, Wong WH, Welch WR, Berkowitz RS, Birrer MJ. A gene signature predictive for outcome in advanced ovarian cancer identifies a survival factor: microfibril-associated glycoprotein 2.Cancer Cell. 16(6) : 521-32, 2009.
Balasubramanian L, Sham JS, Yip KP. Calcium signaling in vasopressin-induced aquaporin-2 trafficking.Pflügers Archiv : European journal of physiology. 456(4) : 747-54, 2008.
Balasubramanian L, Yip KP, Hsu TH, Lo CM. Impedance Analysis of Renal Vascular Smooth Muscle Cells.American journal of physiology. Cell physiology. , 2008.
Ditlevsen S, Yip KP, Marsh DJ, Holstein-Rathlou NH. Parameter estimation of feedback gain in a stochastic model of renal hemodynamics: differences between spontaneously hypertensive and Sprague-Dawley rats.American journal of physiology. Renal physiology. 292(2) : F607-16, 2007.
Balasubramanian L, Ahmed A, Lo CM, Sham JS, Yip KP. Integrin-mediated mechanotransduction in renal vascular smooth muscle cells: activation of calcium sparks.American journal of physiology. Regulatory, integrative and comparative physiology. 293(4) : R1586-94, 2007.
Sosnovtseva OV, Pavlov AN, Mosekilde E, Yip KP, Holstein-Rathlou NH, Marsh DJ. Synchronization among mechanisms of renal autoregulation is reduced in hypertensive rats. , 2007.
Leong PK, Yang LE, Landon CS, McDonough AA, Yip KP. Phenol injury-induced hypertension stimulates proximal tubule Na+/H+ exchanger activity.American journal of physiology. Renal physiology. 290(6) : F1543-50, 2006.
Raghavan R, Chen X, Yip KP, Marsh DJ, Chon KH. Interactions between TGF-dependent and myogenic oscillations in tubular pressure and whole kidney blood flow in both SDR and SHR.American journal of physiology. Renal physiology. 290(3) : F720-32, 2006.
Yip KP. Epac-mediated Ca(2+) mobilization and exocytosis in inner medullary collecting duct.American journal of physiology. Renal physiology. 291(4) : F882-90, 2006.
Umesh A, Thompson MA, Chini EN, Yip KP, Sham JS. Integrin ligands mobilize Ca2+ from ryanodine receptor-gated stores and lysosome-related acidic organelles in pulmonary arterial smooth muscle cells.The Journal of biological chemistry. 281(45) : 34312-23, 2006.
Chon KH, Raghavan R, Chen YM, Marsh DJ, Yip KP. Interactions of TGF-dependent and myogenic oscillations in tubular pressure.American journal of physiology. Renal physiology. 288(2) : F298-307, 2005.
Yang XR, Lin MJ, Yip KP, Jeyakumar LH, Fleischer S, Leung GP, Sham JS. Multiple ryanodine receptor subtypes and heterogeneous ryanodine receptor-gated Ca2+ stores in pulmonary arterial smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology. 289(2) : L338-48, 2005.
Ditlevsen S, Yip KP, Holstein-Rathlou NH. Parameter estimation in a stochastic model of the tubuloglomerular feedback mechanism in a rat nephron.Mathematical biosciences. 194(1) : 49-69, 2005.
Marsh DJ, Sosnovtseva OV, Pavlov AN, Yip KP, Holstein-Rathlou NH. Frequency encoding in renal blood flow regulation.American journal of physiology. Regulatory, integrative and comparative physiology. 288(5) : R1160-7, 2005.
Yip KP. Flash photolysis of caged nitric oxide inhibits proximal tubular fluid reabsorption in free-flow nephron.American journal of physiology. Regulatory, integrative and comparative physiology. 289(2) : R620-R626, 2005.
Lin MJ, Leung GP, Zhang WM, Yang XR, Yip KP, Tse CM, Sham JS. Chronic hypoxia-induced upregulation of store-operated and receptor-operated Ca2+ channels in pulmonary arterial smooth muscle cells: a novel mechanism of hypoxic pulmonary hypertension.Circulation research. 95(5) : 496-505, 2004.
Zhang WM, Yip KP, Lin MJ, Shimoda LA, Li WH, Sham JS. ET-1 activates Ca2+ sparks in PASMC: local Ca2+ signaling between inositol trisphosphate and ryanodine receptors.American journal of physiology. Lung cellular and molecular physiology. 285(3) : L680-90, 2003.
Yip KP, Tsuruoka S, Schwartz GJ, Kurtz I. Apical H(+)/base transporters mediating bicarbonate absorption and pH(i) regulation in the OMCD.American journal of physiology. Renal physiology. 283(5) : F1098-104, 2002.
Zou R, Cupples WA, Yip KP, Holstein-Rathlou NH, Chon KH. Time-varying properties of renal autoregulatory mechanisms.IEEE transactions on bio-medical engineering. 49(10) : 1112-20, 2002.
Yip KP, Kurtz I. Confocal fluorescence microscopy measurements of pH and calcium in living cells.Methods in cell biology. 70: 417-27, 2002.
Yip KP. Coupling of vasopressin-induced intracellular Ca2+ mobilization and apical exocytosis in perfused rat kidney collecting duct.The Journal of physiology. 538(Pt 3) : 891-9, 2002.
Chou CL, Yip KP, Michea L, Kador K, Ferraris JD, Wade JB, Knepper MA. Regulation of aquaporin-2 trafficking by vasopressin in the renal collecting duct. Roles of ryanodine-sensitive Ca2+ stores and calmodulin.The Journal of biological chemistry. 275(47) : 36839-46, 2000.
Yip KP, Wagner AJ, Marsh DJ. Detection of apical Na(+)/H(+) exchanger activity inhibition in proximal tubules induced by acute hypertension.American journal of physiology. Regulatory, integrative and comparative physiology. 279(4) : R1412-8, 2000.
Pushkin A, Yip KP, Clark I, Abuladze N, Kwon TH, Tsuruoka S, Schwartz GJ, Nielsen S, Kurtz I. NBC3 expression in rabbit collecting duct: colocalization with vacuolar H+-ATPase.The American journal of physiology. 277(6 Pt 2) : F974-81, 1999.
Yip KP, Tse CM, McDonough AA, Marsh DJ. Redistribution of Na+/H+ exchanger isoform NHE3 in proximal tubules induced by acute and chronic hypertension.The American journal of physiology. 275(4 Pt 2) : F565-75, 1998.
Quayle AJ, Porter EM, Nussbaum AA, Wang YM, Brabec C, Yip KP, Mok SC. Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract.The American journal of pathology. 152(5) : 1247-58, 1998.
Cutaia MV, Parks N, Centracchio J, Rounds S, Yip KP, Sun AM. Effect of hypoxic exposure on Na+/H+ antiport activity, isoform expression, and localization in endothelial cells.The American journal of physiology. 275(3 Pt 1) : L442-51, 1998.
Yip KP, Marsh DJ. An Arg-Gly-Asp peptide stimulates constriction in rat afferent arteriole.The American journal of physiology. 273(5 Pt 2) : F768-76, 1997.
Sun AM, Liu Y, Dworkin LD, Tse CM, Donowitz M, Yip KP. Na+/H+ exchanger isoform 2 (NHE2) is expressed in the apical membrane of the medullary thick ascending limb.The Journal of Membrane Biology. 160(1) : 85-90, 1997.
Yip KP, Marsh DJ. [Ca2+]i in rat afferent arteriole during constriction measured with confocal fluorescence microscopy.The American journal of physiology. 271(5 Pt 2) : F1004-11, 1996.
Yip KP, Holstein-Rathlou NH. Chaos and non-linear phenomena in renal vascular control.Cardiovascular research. 31(3) : 359-70, 1996.
Zhang Y, Mircheff AK, Hensley CB, Magyar CE, Warnock DG, Chambrey R, Yip KP, Marsh DJ, Holstein-Rathlou NH, McDonough AA. Rapid redistribution and inhibition of renal sodium transporters during acute pressure natriuresis.The American journal of physiology. 270(6 Pt 2) : F1004-14, 1996.
Yip KP, Kurtz I. NH3 permeability of principal cells and intercalated cells measured by confocal fluorescence imaging.The American journal of physiology. 269(4 Pt 2) : F545-50, 1995.
Chen YM, Yip KP, Marsh DJ, Holstein-Rathlou NH. Magnitude of TGF-initiated nephron-nephron interactions is increased in SHR.The American journal of physiology. 269(2 Pt 2) : F198-204, 1995.
Smedley G, Yip KP, Wagner A, Dubovitsky S, Marsh DJ. A laser Doppler instrument for in vivo measurements of blood flow in single renal arterioles.IEEE transactions on bio-medical engineering. 40(3) : 290-7, 1993.
Yip KP, Holstein-Rathlou NH, Marsh DJ. Mechanisms of temporal variation in single-nephron blood flow in rats.The American journal of physiology. 264(3 Pt 2) : F427-34, 1993.
Yip KP, Holstein-Rathlou NH, Marsh DJ. Dynamics of TGF-initiated nephron-nephron interactions in normotensive rats and SHR.The American journal of physiology. 262(6 Pt 2) : F980-8, 1992.
Buchanan TA, Sipos GF, Gadalah S, Yip KP, Marsh DJ, Hsueh W, Bergman RN. Glucose tolerance and insulin action in rats with renovascular hypertension.Hypertension. 18(3) : 341-7, 1991.
Yip KP, Holstein-Rathlou NH, Marsh DJ. Chaos in blood flow control in genetic and renovascular hypertensive rats.The American journal of physiology. 261(3 Pt 2) : F400-8, 1991.
Marsh DJ, Yip KP, Källskog O, Holstein-Rathlou NH. Oscillations and more complex dynamics in tubuloglomerular feedback.Kidney International. Supplement. 32: S94-7, 1991.
