Hematology Faculty

Harinder S. Juneja, M.D.
Professor & Division Director

Biographical Sketch

6431 Fannin, MSB 5.016
Houston, Texas 77030
Tel: 713-500-6773
Fax: 713-500-6812
Email: Harinder.S.Juneja@uth.tmc.edu

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Miguel Escobar, M.D.
Associate Professor

Biographical Sketch

6655 Travis, HMC 400
Houston, Texas 77030-1312
Tel: 713-500-8360
Fax: 713-500-8364
Email: Miguel.Escobar@uth.tmc.edu

Research Interests

My interests are in clinical and translational research involving bleeding and hemostasis in patients with hemophilia and other congenital and acquired bleeding disorders.

Recent Publications

• Champion H.R, Fingerhut, A., Escobar, M.A., Weiskopf, R. The Role of Data and Safety Monitoring in Acute Trauma Resuscitation Research. Journal of the American College of Surgeons. 204:73-83, 2007.
• Planque, S., Mitsuda, Y., Taguchi, H., Salas, M., Morris, M.-K., Nishiyama, Y., Kyle, R., Okhuysen, P., Escobar, M., Hunter, R., Sheppard, H.W., Hanson, C., Paul, S. Characterization of gp120 hydrolysis by IgA antibodies from humans without HIV infection. AIDS Research and Human Retroviruses. 23(12):1541-1553, 2007.
• Hallevi, H., Gonzales, N.R., Barreto, A.D., Martin-Schild, S., Albright, K.C., Noser, E.A., Illoh, K., Khaja, A.M., Allison, T., Escobar, M., Shaltoni, H.M., and Grotta, J.C. The Effect of Activated Factor VII for Intracerebral Hemorrhage Beyond Three Hours vs Within Three Hours. Stroke. 39(2):473-475, 2008.
• Hallevi, H., Albright, K.C., Martin-Schild, S., Barreto, A.D., Savitz, S.I., Escobar, M.A., Gonzales, N.R., Noser, E.A., Illoh, Kachi, Grotta, J.C.; On behalf of the VISTA investigators. Anticoagulation After Cardioembolic Stroke: To Bridge or Not to Bridge? Accepted: Archives of Neurology. Arch Neurol. 65(9):1169-73, 2008.
• Pivalizza, E.G., Escobar, M.A.. Thrombelastograph and RoTEM guided Factor VIIa Therapy in a Surgical Patient with Severe Hemophilia and Factor VIII Inhibitor. Anesthesia & Analgesia, 107(2):398-401, 2008.
• Marcos, L.A., Majid, R., Hamzeh, Nabeel, Mehta Niraj, Escobar, M. An Acute Intracerebral Vein Thromboses in AIDS. A Case Report. International Journal of STD and AIDS. 19:59-61, 2008.
• Planque, S., Escobar, MA., Smith, KC., Taguchi, H., Nishiyama, Y., Donnachie, E., Pratt, KP., Paul, S. Covalent inactivation of Factor VIII antibodies by an electrophilic FVIII analog. Journal of Biological Chemistry. 283(18):11876-11886, 2008.
• Bolliger, D., Szlam, F., Molinaro, R.J., Escobar, M.A., et.al. Thrombin generation and fibrinolysis in anti-factor IX treated blood and plasma spiked with factor VIII inhibitor bypassing activity or recombinant factor VIIa. Haemophilia 2009, Dec 29 (Epub ahead print)
• Roberts, H.R. and Escobar, M.A., Less Common Congenital Disorders of Hemostasis, in Consultative Hemostasis and Thrombosis, CS Kitchens, et al., editors. W.B. Saunders Company. Second Edition 2007.
• Escobar, M.A., Diagnosis and Management of Acquired Bleeding Disorders: Vitamin K Antagonists in Evidence-based Hematology, Crowther, M., Ginsberg, J., et al., editors. Blackwell Publishing. 2008.
• Roberts, H.R., Key, N., Escobar, M.A. Hemophilia A and Hemophilia B, in Williams Hematology. Eighth edition. Beutler E., et al editors. McGraw Hill. 2010.
• Escobar M.A. Products used to treat haemophilia: Dosing, in Textbook of Haemophilia. C Lee, K Hoots and E Berntop, editors. Blackwell Publishing. 2010.

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Modupe Idowu, M.D.
Assistant Professor

Biographical Sketch

6431 Fannin, MSB 5.287
Houston, Texas 77030
Tel: 713-500-6764
Fax: 713-500-6812
Email: Modupe.Idowu@uth.tmc.edu

Research Interests

My interests are in treating patients with sickle cell anemia, myeloproliferative neoplasm, thrombotic disorders, and hematologic malignancy including lymphoproliferative disorders, plasma cell dyscracias, and leukemias.

I have special interests in clinical and translational research involving sickle cell anemia and thrombotic disorders. I have previously done research work on the use of hydroxyurea in sickle cell anemia. I am currently working, in collaboration with Dr. Juneja (Hematology division) and Dr. Yang Xia of the Department of Biochemistry and Molecular Biology, on the role of adenosine in pathophysiology of sickle cell anemia. Our data shows that excess adenosine can increase polymerization of hemoglobin S.

I will also be evaluating the effect of sickle cell anemia on patients’ academic achievement and job performance. This project will be in collaboration with The University of Texas School of Public Health.

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Richard Kulmacz, Ph.D.
Professor

Biographical Sketch

6431 Fannin, MSB 5.288
Houston, Texas 77030
Tel: 713-500-6772
Fax: 713-500-6810
Email: Richard.J.Kulmacz@uth.tmc.edu

Research Interests

Eicosanoids are very potent cellular signalling molecules derived from polyunsaturated fatty acids. Their name comes from the prototypical polyunsaturated fatty acid, eicosatetraenoic acid (arachidonic acid), and the class includes prostaglandins, leukotrienes, hydroxy fatty acids, and epoxy fatty acids. Eicosanoids have been implicated in a wide variety of pathophysiological processes, including carcinogenesis, hemostasis, inflammation, renal function, reproduction, and sleep/wake cycles. My general interest is in understanding at the molecular level how eicosanoid biosynthesis is accomplished and how it is regulated.

A major control point in eicosanoid biosynthesis is the initial oxygenation of fatty acid to form a lipid hydroperoxide, catalyzed by one of several fatty acid oxygenases. My lab’s focus at present is on two major areas: the roles of substrate structure, redox environment and human enzyme polymorphisms on regulation of prostaglandin synthesis, and the relationship between structure and function among human cytochrome b561 family members.

Recent Publications

• Rogge, C.E., Ho, B., Liu, W., Kulmacz, R.J., and Tsai, A.-L. Role of Tyr348 in Tyr385 radical dynamics and cyclooxygenase inhibitor interactions in prostaglandin H synthase-2. Biochemistry 45:523-532, 2006.
• Liu, W., Cao, D., Oh, S.F., Serhan, C.N., and Kulmacz, R.J. Divergent cyclooxygenase responses to fatty acid structure and peroxide levels in fish and mammalian prostaglandin H synthases. FASEB J. 20:1097-1108, 2006.
• Liu, W., Wang, L.-H., Fabian, P., Hayashi, Y., McGinley, C.M., van der Donk, W.A., Kulmacz, R.J. Arabidopsis thaliana fatty acid alpha-dioxygenase-1 evaluation of substrates, inhibitors and amino-terminal function. Plant Physiol. Biochem. 44:284-293, 2006.
• Wu, G., Rogge, C.E., Wang, J.-S., Kulmacz, R.J., Palmer, G., Tsai. A.-L. Oxyferryl heme and not tyrosyl radical is the likely culprit in prostaglandin H synthase-1 peroxidase inactivation. Biochemistry 46:534-542, 2007.
• Poole, E.M., Bigler, J., Whitton, J., Sibert, J.G., Kulmacz, R.J., Potter, J.D., Ulrich, C.M. Genetic variability in prostaglandin synthesis, fish intake, and risk of colorectal polyps. Carcinogenesis 28:1259-1263,2007.
• Liu W, Rogge CE, Kamensky Y, Tsai AL, Kulmacz RJ. Development of a bacterial system for high yield expression of fully functional adrenal cytochrome b561. Protein Expr Purif 56:145-152, 2007.
• Kamensky Y, Liu W, Tsai AL, Kulmacz RJ, Palmer G. Axial ligation and stoichiometry of heme centers in adrenal cytochrome b561. Biochemistry 46:8647-8658, 2007.
• Doyen JR, Yucer N, Lichtenberger LM, Kulmacz RJ. Phospholipid actions on PGHS-1 and -2 cyclooxygenase kinetics. Prostaglandins Other Lipid Mediat 85:134-143, 2008.
• Liu W, Rogge CE, da Silva GFZ, Shinkarev VP, Tsai AL, Kamensky Y, Palmer G, and Kulmacz RJ. His92 and His110 Selectively Affect Different Heme Centers of Adrenal Cytochrome b561. Biochim Biophys Acta 1777:1218-1228, 2008.
• Rogge CE, Liu W, Kulmacz RJ, Tsai AL. Peroxide-induced radical formation at Tyr385 and Tyr504 in human PGHS-1. J Inorg Biochem 103:912-922, 2009.
• Poole EM, Hsu L, Xiao L, Kulmacz RJ,Carlson CS, Rabinovitch PS, Potter JD, Ulrich CM Genetic variation in prostaglandin E2 synthesis and signaling, prostaglandin dehydro genase, and risk of colorectal adenoma. Cancer Epidemiology, Biomarkers and Prevention, in press, 2009.
• Tsai AL, Kulmacz RJ. Prostaglandin H synthase: resolved and unresolved mechanistic issues. Arch Biochem Biophys 493:103-124, 2009.
• Wu G, Tsai AL, Kulmacz RJ. Cyclooxygenase competitive inhibitors alter tyrosyl radical dynamics in prostaglandin H synthase-2. Biochemistry 48:11902-11911, 2009.

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Ah-Lim Tsai, Ph.D.
Professor

Biographical Sketch

6431 Fannin, MSB 5.290
Houston, Texas 77030
Tel: 713-500-6771
Fax: 713-500-6810
Email: Ah-Lim.Tsai@uth.tmc.edu

Ongoing Research Topics

The central theme of my research is to understand the reaction mechanism of several crucial heme-containing proteins that are involved in regulatory functions and the pathological processes of the cardiovascular system. Prostaglandins and nitric oxide (NO) are two important mediators in hemostasis. For example, prostacyclin and NO released by endothelial cells are strong vasodilators and potent inhibitors of platelet aggregation, whereas thromboxane and prostaglandin G2/H2 released by platelets are potent agonists of platelet aggregation and vasoconstriction. All these compounds are short-lived autocoids. A balanced production and timely release of these potent hormones are crucial in maintaining a normal vascular tone and an imbalanced synthesis of these mediators usually leads to pathological conditions.

Expertise

Metelloenzymes, esp. Hemeproteins Electron transfer and redox reactions Enzyme kinetics, mainly transient kinetics (stopped-flow, rapid-freezing and rapid quench) Computer modeling and simulation Bioenergetics Mitochondria (structure and function) Membrane-bound proteins Prostaglandins, receptors, binding proteins and signal transduction Prostaglandin H synthase and nonsteroidal anti-inflammatory agents Nitric oxide and nitric oxide synthase Spectroscopic methods (UV-VIS, fluorescence, EPR and MCD).

Recent Publications

• Wu, G., Rogge, C.E., Wang, J.-S., Kulmacz, R.J., Palmer, G., and Tsai, A.-L. Oxyferryl heme and not tyrosyl radical is the likely culprit in prostaglandin H synthase-1 peroxidase inactivation. Biochemistry, 46:534-542, 2007.
• Cardounel, A.J., Cui, H., Johnson, W., Kearns, P., Tsai, A.-L., Berka, V., and Zweier, J.A. ADMA and L-NMMA regulate endothelial NOS activity: predicting methylarginine effects on nitric oxide production. J. Biol. Chem. 282:879-887, 2007.
• Beaumont, B., Lambry, J.-C., Gautier, C., Robin, A.-C., Gmouh, S., Berka, V., Tsai, A.-L., Blanchard-Desce, M., and Slama-Schwok, A. Synchronous photo-initiation of endothelial NO Synthase activity by a nanotrigger targeted at its NADPH site. J. Am. Chem. Soc. 129:2178-2186, 2007.
• Sasaki, J., Phillips, B., Chen, X., Eps, N.V., Tsai, A.-L., Hubbell, W.L., and Spudich, J.L. Two Dark Conformations Govern Color-Sensitive Photosignaling by the Sensory Rhodopsin I-HtrI Complex. Biophysical J. 92:4045-4053, 2007.
• Yeh, H.C., Tsai, A.-L., and Wang, L.-H. Reaction mechanisms of 15-hydroperoxy-eicosatetraenoic acid catalyzed by human prostacyclin and thromboxane synthases. Arch. Biochem. Biophys., 46:159-168, 2007.
• Liu, W, Rogge, C.E., Kamensky, Y., Tsai, A.-L., and Kulmacz, R.J. Development of a bacterial system for high yield expression of fully functional adrenal cytochrome b(561). Protein Expr. Purif. 56:145-152, 2007.
• Kamensky, Y., Liu, W., Tsai, A.-L., Kulmacz, R.J., and Palmer, G. Axial ligation and stoichiometry of heme centers in adrenal cytochrome b561. Biochemistry 46:8647-8658, 2007.
• Berka, V., Wang, L.-H., and Tsai, A.-L. Oxygen-induced radical intermediates in nNOS oxygenase domain regulated by L-arginine, tetrahydrobiopterin, and thiol. Biochemistry 47:405-420, 2008.
• Yeh, H.-C., Hsu, P.Y., Tsai, A.-L, and Wang, L.-H. Spectroscopic characterization of the oxyferrous complex of prostacyclin synthase in solution and in trapped sol-gel matrix. FEBS J. 275:2305-2314, 2008.
• Liu, W., Rogge, C.E., da Silva, G.F., Shinkarev, V.P., Tsai, A.-L., Kamensky, Y., and Palmer G, Kulmacz RJ. His92 and His110 selectively affect different heme centers of adrenal cytochrome b(561). Biochim Biophys Acta. 1777:1218-1228, 2008.
• Yeh, H.-C., Gerfen, G.J., Wang, J.-S., Tsai, A.-L., and Wang, L.-H. Characterization of the Peroxidase Mechanism upon the Reaction of prostacyclin Synthase with Peracetic Acid. Identification of a Tyrosyl Radical Intermediate. Biochemistry 48:917-928, 2009.
• Rogge, C.E., Liu, W., Kulmacz, R.J., and Tsai, A.-L. Peroxide-induced radical formation at Tyr385 and Tyr504 in human PGHS-1. J. Inorg. Biochem., 103:912-922, 2009.
• Wu G, Tsai A.-L, Kulmacz RJ. Cyclooxygenase competitive inhibitors alter tyrosyl radical dynamics in prostaglandin h synthase-2. Biochemistry 48:11902-11911.
• Tsai, A.-L., and Kulmacz, R.J. Prostaglandin H synthase: resolved and unresolved mechanistic issues.  Arch. Biochem. Biophys. 493:103-124, 2010.

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Lee-Ho Wang, Ph.D.
Associate Professor

Biographical Sketch

6431 Fannin, MSB 5.216
Houston, Texas 77030
Tel: 713-500-6794
Fax: 713-500-6810
Email: Lee-Ho.Wang@uth.tmc.edu

Research Interests

My interests are in the investigation of structure-function relationships of thromboxane synthase and prostacyclin synthase.

Recent Publications

• Yeh, H.-C., Tsai, A.-L. and Wang, L.-H. Reaction mechanisms of 15-hydroperoxy-eicosatetraenoic acid catalyzed by human prostacyclin and thromboxane synthases. Arch. Biochem. Biophys. 461:159-168, 2007.
• Berka, V., Wang, L.-H. and Tsai, A.-L. Oxygen-induced radical intermediates in the nNOS oxygenase domain regulated by l-arginine, tetrahydrobiopterin and thiol. Biochemistry. 47:405-420, 2008.
• Li, Y.-C., Chiang, C.-W., Yeh, H.-C., Hsu, P.-Y., Whitby, F. G., Wang, L.-H. and Chan, N.-L. Structures of prostacyclin synthase and its complexes with substrate-analog and inhibitor reveal a ligand-specific heme conformation change. J. Biol. Chem. 283:2917-2926, 2008.
• Yeh, H.-C., Hsu, P.-Y. Tsai, A.-L. and Wang, L.-H. Spectroscopic characterization of oxyferrous complex of prostacyclin synthase in solution and in trapped sol-gel matrix. FEBS J. 275:2305-2314, 2008.
• Yeh, H.-C., Gerfen, G. J., Wang, J.-S., Tsai, A.-L. and Wang, L.-H. Characterization of the Peroxidase Mechanism upon Reaction of Prostacyclin Synthase with Peracetic Acid. Identification of a Tyrosyl Radical Intermediate. Biochemistry. 48:917-928, 2009.

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Gang Wu, Ph.D.
Instructor

Biographical Sketch

6431 Fannin, MSB 3.324
Houston, Texas 77030
Tel: 713-500-6802
Fax: 713-500-6812
Email: Gang.Wu@uth.tmc.edu

Research Interests

My research interests are in the catalytical mechanism of prostaglandin H synthase.

Recent Publications

• Wu, G. Berka, V. and Tsai, A.-L. “Binding kinetics of calmodulin with target peptides of three nitric oxide synthase isozymes”, Journal of Inorganic Biochemistry (2011) accepted.
• Walkiewicz, K., Davlieva, M., Wu, G. and Shamoo, Y. “Crystal structure of Bacteroides thetaiotaomicron TetX2, a tetracycline degrading monooxygenase at 2.8 Å resolution”, PROTEINS: Structure, Function, and Bioinformatics (2011) 79, 2335-2340.
• Liu, W., Wu, G., Tsai, A.-L. and Kulmacz, R.J. “High-yield production, purification and characterization of functional human duodenal cytochrome b in an Escherichia coli system”, Protein Expression and Purification (2011) in press (doi:10.1016/j.pep.2011.04.001).
• Liu, W., da Silva, G., Wu, G., Palmer, G., Tsai, A.-L. and Kulmacz, R. J., “Functional and Structural Roles of Residues in the Third Extra-membrane Segment (EM3) of Adrenal Cytochrome b₅₆₁”, Biochemistry (2011) 50, 3149-3160.
• Tsai, A.-L., Wu, G., Rogge, C.E., Lü, J., Peng, S., van der Donk, W.A., Palmer, G., Gerfen, G.J. and Kulmacz, R.J. “Structural comparisons of arachidonic acid-induced radicals formed by prostaglandin H synthase-1 and -2”, Journal of Inorganic Biochemistry (2011) 105, 248-256.
• Lü, J., Rogge, C.E., Wu, G., Kulmacz, R.J., van der Donk, W.A. and Tsai, A.-L. “Cyclooxygenase reaction mechanism of PGHS ------- evidence for a reversible transition between a pentadienyl radical and a new tyrosyl radical by nitric oxide trapping”, Journal of Inorganic Biochemistry (2011) 105, 238-247.
• Wu, G., Lü, J., van der Donk, W.A., Kulmacz, R.J. and Tsai, A.-L. “Cyclooxygenase reaction mechanism of prostaglandin H synthase from deuterium kinetic isotope effects”, Journal of Inorganic Biochemistry (2011) 105, 264-272.
• Miller, C., Davlieva, M., Wilson, C.J., White, K., Counago, R., Wu, G., Myers, J.C., Wittung-Stafshede, P. and Shamoo Y. “Experimental evolution of adenylate kinase reveals contrasting strategies toward protein thermostability”, Biophysical Journal (2010) 99, 887-896.
• Wu, G., Tsai, A.-L. and Kulmacz, R. J. “Cyclooxygenase competitive inhibitors alter tyrosyl radical dynamics in prostaglandin h synthase-2”, Biochemistry (2009) 48, 11902-11911.
• Wu, G., Rogge, C.E., Wang, J.S., Kulmacz, R.J., Palmer, G. and Tsai, A.-L. L. “Oxyferryl Heme and not Tyrosyl Radical is the likely Culpit in Prostaglandin H Synthase-1 Inactivation”, Biochemistry, (2007), 46, 534-542.

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Kenneth K. Wu, M.D., Ph.D.
Professor Emeritus

Biographical Sketch

Current Position:
President of National Health Research Institutes
Taiwan 35, Keyan Road, Zhunan Township, Miaoli County
350 Taiwan
Tel: 886-37-246-166, Ext. 31000