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BIOGRAPHICAL SKETCH Ora A. Weisz, Ph.D. Professor of ...

BIOGRAPHICAL SKETCH Ora A. Weisz, Ph.D. Professor of ...

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<strong>BIOGRAPHICAL</strong> <strong>SKETCH</strong><br />

Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.<br />

Follow this format for each person. DO NOT EXCEED FOUR PAGES.<br />

NAME<br />

<strong>Ora</strong> A. <strong>Weisz</strong>, <strong>Ph</strong>.D.<br />

eRA COMMONS USER NAME<br />

OWEISZ<br />

POSITION TITLE<br />

<strong>Pr<strong>of</strong>essor</strong> <strong>of</strong> Medicine<br />

and Cell Biology and <strong>Ph</strong>ysiology<br />

EDUCATION/TRAINING (Begin with baccalaureate or other initial pr<strong>of</strong>essional education, such as nursing, and include postdoctoral training.)<br />

INSTITUTION AND LOCATION<br />

DEGREE<br />

(if applicable)<br />

YEAR(s)<br />

Yale University, New Haven, CT B.S. 1984<br />

Johns Hopkins School <strong>of</strong> Medicine, Baltimore,<br />

MD<br />

<strong>Ph</strong>.D. 1990<br />

FIELD OF STUDY<br />

Mol. Biophys. and<br />

Biochem./History<br />

Biochemistry,<br />

Cellular and Mol. Biol.<br />

A. Personal Statement<br />

I have been working in the area <strong>of</strong> polarized membrane traffic for 20 years, and have published extensively on<br />

the signals and mechanisms that regulate protein delivery to the apical surface <strong>of</strong> kidney cells. During this time<br />

I have mentored numerous graduate students and fellows, many <strong>of</strong> whom have transitioned to independent<br />

academic positions. I am fully committed to assisting trainees to develop a unique skill set that will facilitate<br />

their success as independent researchers.<br />

B. Positions and Honors<br />

1990-95: Postdoctoral Fellow, The Johns Hopkins University School <strong>of</strong> Medicine, Baltimore, MD<br />

1995 to 2001: Assistant <strong>Pr<strong>of</strong>essor</strong>, Renal-Electrolyte Division, Department <strong>of</strong> Medicine and Department <strong>of</strong><br />

Cell Biology and <strong>Ph</strong>ysiology, Univ. <strong>of</strong> Pittsburgh School <strong>of</strong> Medicine<br />

2001 to 2007: Associate <strong>Pr<strong>of</strong>essor</strong>, Univ. <strong>of</strong> Pittsburgh School <strong>of</strong> Medicine<br />

2004 to 2007: Assistant Director, Office <strong>of</strong> Academic Career Devt, Univ. <strong>of</strong> Pittsburgh Health Sciences<br />

2007 to present: Vice Chair <strong>of</strong> Faculty Development, Department <strong>of</strong> Medicine, Univ. <strong>of</strong> Pittsburgh<br />

2007 to present: <strong>Pr<strong>of</strong>essor</strong>, Univ. <strong>of</strong> Pittsburgh School <strong>of</strong> Medicine<br />

2000 University <strong>of</strong> Pittsburgh Senior Vice Chancellor’s Research Seminar<br />

2001-2007 Editorial Board, American Journal <strong>of</strong> <strong>Ph</strong>ysiology – Renal<br />

2002-present Editorial Board, American Journal <strong>of</strong> <strong>Ph</strong>ysiology – Cell <strong>Ph</strong>ysiology<br />

2002, 2004, 2006 American Society <strong>of</strong> Nephrology annual meeting abstract program committee<br />

2002 NIH study section, General Medicine B, ad hoc<br />

2003, 2004, 2007 NIH study section, NIDDK Special Emphasis Panel<br />

2004 NIH study section, Cardiovascular, Respiratory, Blood, Digestive and Renal Systems<br />

2004-07 NIH study section, Gastrointestinal, Renal, and Bone Pathophysiology<br />

2005-2007 American <strong>Ph</strong>ysiological Society Joint Program Committee, member at large<br />

2007-2009 American Heart Association (Mid-Atlantic affiliate) study section<br />

2007 NIH study section, Membrane Biology and Protein Processing, ad hoc<br />

2007 NHLBI-DIR Board <strong>of</strong> Scientific Counselor Site Review Meeting<br />

2007-2008 American Society <strong>of</strong> Nephrology annual meeting program committee<br />

2007 American Journal <strong>of</strong> <strong>Ph</strong>ysiology Star Reviewer<br />

2008-2012 NIH study section, CMBK<br />

2009- Editorial Board, <strong>Ph</strong>ysiological Reviews (ASCB representative)<br />

C. Selected Publications (from a total <strong>of</strong> 60; 28 since 2005)<br />

Henkel, J.R., Gibson, G.A., Poland, P.A., Ellis, M.A., Hughey, R.P., and <strong>Weisz</strong>, O.A. (2000) Influenza M2<br />

proton channel activity selectively inhibits TGN release <strong>of</strong> apical membrane and secreted proteins in polarized<br />

MDCK cells. J. Cell Biol. 148:495-504. PMID: 10662775<br />

Ihrke, G., Bruns, J.R., Luzio, J.P., and <strong>Weisz</strong>, O.A. (2001) A novel lysosomal delivery route via the apical<br />

surface identified by the trafficking <strong>of</strong> endolyn in MDCK cells. EMBO J. 20:6256-6264. PMID: 11707397<br />

Lee, E., Marcucci, M., Daniell, L., Pypaert, M., <strong>Weisz</strong>, O.A., Ochoa, G.-C., Farsad, K., Wenk, M.R., and De<br />

Camilli, P. (2002) Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle. Science 297:1193-1196. PMID:


12183633<br />

Potter, B.A., Ihrke, G., Bruns, J.R., Weixel, K.M., and <strong>Weisz</strong>, O.A. (2004) Specific N-glycans direct apical<br />

delivery <strong>of</strong> transmembrane, but not soluble or GPI-anchored forms <strong>of</strong> endolyn in MDCK cells. Mol. Biol. Cell.<br />

15:1407-1416. PMID: 14699065<br />

Potter, B.A., Weixel, K.M., Bruns, J.R., Ihrke, G., and <strong>Weisz</strong>, O.A. (2006) N-Glycans mediate apical recycling<br />

<strong>of</strong> the sialomucin endolyn in polarized MDCK cells. Traffic 7:146-154. PMID: 16420523<br />

Guerriero, C.J., Weixel, K.M., Bruns, J.R., and <strong>Weisz</strong>, O.A. (2006) <strong>Ph</strong>osphatidylinositol 5-kinase stimulates<br />

apical biosynthetic delivery via an Arp2/3-dependent mechanism. J. Biol. Chem. 281:15376-15384. PMID:<br />

16601114<br />

Blumental-Perry, A., Haney, C.J., Weixel, K.M., Watkins, S.C., <strong>Weisz</strong>, O.A., and Aridor, M. (2006)<br />

<strong>Ph</strong>osphatidylinositol 4-phosphate formation at ER exit sites regulates ER export. Dev. Cell. 11:671-682.<br />

PMID: 16935843<br />

Cresawn, K.O., Potter, B.A., Oztan, A., Guerriero, C.J., Ihrke, G., Goldenring, J.R., Apodaca, G, and <strong>Weisz</strong>,<br />

O.A. (2007) Differential involvement <strong>of</strong> endocytic compartments in the biosynthetic traffic <strong>of</strong> apical proteins.<br />

EMBO J., 26:3737-3748. PMID: 17673908<br />

Miedel, M.T., Rbaibi, Y., Guerriero, C.J., Colletti, G., Weixel, K.M., <strong>Weisz</strong>, O.A.* and Kiselyov, K.* (2008)<br />

Membrane traffic and turnover in TRP-ML1 deficient cells: A revised model for Mucolipidosis Type IV<br />

pathogenesis. J. Exp. Med. 205:1477-1490. PMID: 18504305 *corresponding authors (Cover article)<br />

Khandelwal, P., Ruiz, W.G., Elena Balestreire-Hawryluk, E. <strong>Weisz</strong>, O.A., Goldenring, J.R., and Apodaca, G.<br />

(2008) Rab11a-dependent exocytosis <strong>of</strong> discoidal/fusiform vesicles in bladder umbrella cells. Proc. Natl.<br />

Acad. Sci. USA, 105:15773-15778. PMID: 18843107<br />

D. Research Support:<br />

R01 DK064613 (<strong>Weisz</strong>) 05/01/09 - 04/30/13 Role: PI<br />

NIH/NIDDK<br />

Regulation <strong>of</strong> Polarized Traffic by PI-Metabolizing Enzymes<br />

The aims <strong>of</strong> this proposal are to (1) determine whether apical and basolateral pools <strong>of</strong> PIP 2 are independently<br />

regulated in renal epithelial cells; (2) examine how changes in PIP 2 levels mediated by agonist stimulation <strong>of</strong> G<br />

protein coupled receptors affect polarized endocytosis; and (3) determine how murine PI5KIalpha regulates<br />

apical endocytosis.<br />

R01 DK54407 (<strong>Weisz</strong>) 09/01/98 – 08/31/12 Role: PI<br />

NIH/NIDDK<br />

Regulation <strong>of</strong> Apical Traffic in Renal Epithelial Cells<br />

The aim <strong>of</strong> this project is to understand the mechanisms by which apical membrane traffic is regulated. Major<br />

goals are to identify the cytoplasmic components required for apical vesicle release from the TGN and to<br />

examine the mechanism <strong>of</strong> glycan-dependent apical sorting in polarized epithelial cells.<br />

R01 DK57718 (Johnson) 02/01/02 – 12/31/11 Role: Co-Investigator<br />

NIH/NIDDK<br />

Trafficking and Regulation <strong>of</strong> the Epithelial Na + Channel<br />

This proposal has three specific aims: 1. To characterize the molecular mechanisms involved in ENaC retrieval<br />

from apical membrane; 2. To characterize the pathways and regulation <strong>of</strong> ENaC recycling; 3. To characterize<br />

the cellular site and mechanism <strong>of</strong> non-coordinate regulation.<br />

P30 DK079307 (Kleyman) 09/01/08-07/31/13 Role: Center Assoc. Dir.<br />

NIH/NIDDK<br />

Pittsburgh Center for Kidney Research<br />

The objective <strong>of</strong> the Center is to reinforce and expand interactions among investigators at the University <strong>of</strong><br />

Pittsburgh and colleagues at Mount Sinai School <strong>of</strong> Medicine, to develop new directions <strong>of</strong> investigation using<br />

electrophysiological, cell biological, molecular, and genetic tools, and to attract new investigators to renalrelated<br />

research. The Center includes four cores and supports pilot and feasibility projects.<br />

1 R01 DK084184-01 (Pastor-Soler) 09/01/09-08/30/14 Role: Co-Investigator<br />

NIH/NIDDK


Regulation <strong>of</strong> V-ATPase by Protein Kinase A and AMP-Activated Kinase<br />

The specific aims <strong>of</strong> this proposal are to determine the mechanisms involved in the modulation <strong>of</strong> V-ATPase<br />

subcellular localization and activity by PKA in ICs and to determine the mechanisms involved in the modulation<br />

<strong>of</strong> V-ATPase subcellular localization and activity by AMPK in ICs.<br />

1 R01 HD058577-01A1 (Kiselyov) 12/01/09 - 11/30/14 Role: Co-Investigator<br />

NIH/NICHD<br />

The TRPML1 Role in Lysosomes<br />

This grant is focused on how defects in the TRP channel family member TRPML1 result in the lysosomal<br />

storage disorder Mucolipidosis type IV. The goals <strong>of</strong> the project are to determine whether TRPML1 regulates<br />

membrane traffic or lysosomal hydrolysis and to identify the ion permeability characteristics <strong>of</strong> TRPML1 that<br />

are critical for its function.<br />

3R01DK054407-12S1 (<strong>Weisz</strong>) 01/01/10-12/31/10 Role: PI<br />

NIH/NIDDK<br />

Regulation <strong>of</strong> Apical Traffic in Renal Epithelial Cells<br />

The central hypothesis <strong>of</strong> this ARRA supplement is to that N glycans play a structural role in apical sorting. Aim<br />

1 will dissect the sorting requirements for secretion <strong>of</strong> an apically secreted protein and aim 2 will determine<br />

whether the role <strong>of</strong> glycan-mediated oligomerization in apical sorting.

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