Center for Matrix Biology - Vanderbilt University and Medical Center

Gilbert W. Moeckel, M.D., Ph.D.
Assistant Professor in the Department of Pathology

	Office Address:	U-2216A MCN
	Mailing Address:	1161 21st Ave South U-2216A MCN Nashville, TN 37232-2561
	Lab address:	MCN C 2317, Dept. of Pathology, Nashville, TN 37232
	Phone:	615-322 1350
		email

Secondary appointment in the Medicine department.

Research Summary

Analgesic nephropathy is an important public health problem in many Western societies. The use of analgesic and nonsteroidal anti-inflammatory drugs (NSAIDs) is increasing. The ingestion of these agents, particularly NSAIDs, has been associated with significant morbidity and mortality. Renal Papillary Necrosis (RPN), the hallmark lesion of analgesic nephropathy, is a pathologic entity that is still poorly understood despite intensive research. The long-term goal of this laboratory is to elucidate the pathologic mechanisms involved in RPN at the molecular level. We have presented a novel hypothesis whereby COX2 inhibitors (i.e. analgesics and NSAIDs) contribute to renal medullary cell death through impairment of cell survival mechanisms that protect kidney cells against hypertonic stress. Our laboratory is currently undertaking studies that examine the impact of COX2 inhibition on transcriptional regulation of cytoprotective genes in mouse medullary interstitial cells under hypertonic conditions. Our studies further aim to investigate in the same cell model the induction of apoptosis by COX2 inhibition and the role of cell survival mechanisms in preventing organized cell death. Finally, the role of cell signaling and nuclear signaling mechanisms involved in COX2-dependent survival mechanisms and the transcriptional regulation of genes involved in these survival strategies will be defined. RPN is a pathologic entity that is still poorly understood. The above mentioned studies address this major gap in our understanding. The fulfillment of our long-term goals will allow insight into mechanistic processes that lead to this important health problem. It is necessary to understand these processes in order to design effective diagnostic procedures, therapeutic approaches and preventive measures for RPN.

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Research Keywords

Apoptosis, Biochemistry, Cell cycle, Diabetes, DNA repair, Enzyme action, Gene regulation, Immunology, Ion transport, Kidney, Kinase, Knockout, Membrane, Molecular medicine, Pathology, Pharmacology, Physiology, Post-transcriptional modification, Renal biology, Signal transduction, Toxicology, Transcription, Transcription factor,

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Associated initiative(s):

Diabetic Complications

Tumor Microenvironment

Career opportunities:
None currently available

Selected Publications

» Cheng, H, Wang, S, Jo, YI, Hao, CM, Zhang, M, Fan, X, Kennedy, C, Breyer, MD, Moeckel, GW, Harris, RC Overexpression of Cyclooxygenase-2 Predisposes to Podocyte Injury J Am Soc Nephrol 2007. :

» Zent, R, Yan, X, Su, Y, Hudson, BG, Borza, DB, Moeckel, GW, Qi, Z, Sado, Y, Breyer, MD, Voziyan, P, Pozzi, A Glomerular injury is exacerbated in diabetic integrin alpha1-null mice Kidney Int 2006. 70:460-70

» Moeckel, GW, Zhang, L, Chen, X, Rossini, M, Zent, R, Pozzi, A Role of integrin alpha1beta1 in the regulation of renal medullary osmolyte concentration Am J Physiol Renal Physiol 2006. 290:F223-31

» Webster, TM, Moeckel, GW, Herrell, SD Second prize: simple method for achieving renal parenchymal hypothermia for pure laparoscopic partial nephrectomy J Endourol 2005. 19:1075-81

» Cheng, H, Zhang, M, Moeckel, GW, Zhao, Y, Wang, S, Qi, Z, Breyer, MD, Harris, RC Expression of mediators of renal injury in the remnant kidney of ROP mice is attenuated by cyclooxygenase-2 inhibition Nephron Exp Nephrol 2005. 101:e75-85

» Lee, W, Glaeser, H, Smith, LH, Roberts, RL, Moeckel, GW, Gervasini, G, Leake, BF, Kim, RB Polymorphisms in human organic anion-transporting polypeptide 1A2 (OATP1A2): implications for altered drug disposition and central nervous system drug entry J Biol Chem 2005. 280:9610-7

» Fisher, Maxwell E, Rossini, Michele, Simmons, Edith, Harris, Raymond C, Moeckel, Gilbert, Zent, Roy A woman with chronic hepatitis C infection and nephrotic syndrome who developed multiple renal lesions after interferon alfa therapy Am J Kidney Dis 2004. 44:567-73

» Lamitina, S Todd, Morrison, Rebecca, Moeckel, Gilbert W, Strange, Kevin Adaptation of the nematode Caenorhabditis elegans to extreme osmotic stress Am J Physiol Cell Physiol 2004. 286:C785-91

» Koshikawa, Naohiko, Schenk, Susann, Moeckel, Gilbert, Sharabi, Andrew, Miyazaki, Kaoru, Gardner, Humphrey, Zent, Roy, Quaranta, Vito Proteolytic processing of laminin-5 by MT1-MMP in tissues and its effects on epithelial cell morphology FASEB J 2004. 18:364-6

» Chen, Xiwu, Moeckel, Gilbert, Morrow, Jason D, Cosgrove, Dominic, Harris, Raymond C, Fogo, Agnes B, Zent, Roy, Pozzi, Ambra Lack of integrin alpha1beta1 leads to severe glomerulosclerosis after glomerular injury Am J Pathol 2004. 165:617-30

» Zhang, Ming-Zhi, Mai, Weiyi, Li, Cunxi, Cho, Sae-youll, Hao, Chuanming, Moeckel, Gilbert, Zhao, Runxiang, Kim, Ingyu, Wang, Jikui, Xiong, Huaqi, Wang, Hong, Sato, Yasunori, Wu, Yizhong, Nakanuma, Yasuni, Lilova, Marusia, Pei, York, Harris, Raymond C, Li, Song, Coffey, Robert J, Sun, Le, Wu, Dianqing, Chen, Xing-Zhen, Breyer, Matthew D, Zhao, Zhizhuang Joe, McKanna, James A, Wu, Guanqing PKHD1 protein encoded by the gene for autosomal recessive polycystic kidney disease associates with basal bodies and primary cilia in renal epithelial cells Proc Natl Acad Sci U S A 2004. 101:2311-6

» Gilbert W. Moeckel, Li Zhang, Agnes B. Fogo, Chuan-Ming Hao, Ambra Pozzi and Matthew D. Breyer COX2 Activity Promotes Organic Osmolyte Accumulation and Adaptation of Renal Medullary Interstitial Cells to Hypertonic Stress Journal of Biological Chemistry 2003. 278:19352-19357

» Wang, Zoufei, Chen, Jian-Kang, Wang, Su-Wan, Moeckel, Gilbert, Harris, Raymond C Importance of functional EGF receptors in recovery from acute nephrotoxic injury J Am Soc Nephrol 2003. 14:3147-54

» Moeckel, Gilbert W, Zhang, Li, Fogo, Agnes B, Hao, Chuan-Ming, Pozzi, Ambra, Breyer, Matthew D COX2 activity promotes organic osmolyte accumulation and adaptation of renal medullary interstitial cells to hypertonic stress J Biol Chem 2003. 278:19352-7

» Gilbert W. Moeckel, Kathy Jabs and Agnes B. Fogo An 11-Year-Old African American Girl With Systemic Lupus Erythematosus And ANCA-Negative Renal Vasculitis American Journal of Kidney Disease 2002. 39:433-438

» HF Cheng, CJ Wang, GW Moeckel, MZ Zhang, JA McKanna and RC Harris A selective cyclooxygenase-2 inhibitor retards progressive renal injury in a model of diabetes and hypertension Kidney International 2002. 62:929-939

» Moeckel, Gilbert W, Jabs, Kathy, Fogo, Agnes B An 11-year-old African-American girl with systemic lupus erythematosus and ANCA-negative renal vasculitis Am J Kidney Dis 2002. 39:433-8

» Moeckel, Gilbert W, Shadman, Ramin, Fogel, Joy M, Sadrzadeh, Sayed M H Organic osmolytes betaine, sorbitol and inositol are potent inhibitors of erythrocyte membrane ATPases Life Sci 2002. 71:2413-24

» Cheng, Hui-Fang, Wang, Connie J, Moeckel, Gilbert W, Zhang, Ming-Zhi, McKanna, James A, Harris, Raymond C Cyclooxygenase-2 inhibitor blocks expression of mediators of renal injury in a model of diabetes and hypertension Kidney Int 2002. 62:929-39

» Gilbert W. Moeckel, Ramin Shadman, Joy M. Fogel and Sayed MH Sadrzadeh Organic Osmolytes betaine, sorbitol and inositol are potent inhibitors of erythrocyte membrane ATPases Life Sciences 2002. 71:2413-2424

» Xiong, Huaqi, Chen, Yongxiong, Yi, Yajun, Tsuchiya, Karen, Moeckel, Gilbert, Cheung, Joseph, Liang, Dan, Tham, Kyi, Xu, Xiaohu, Chen, Xing-Zhen, Pei, York, Zhao, Zhizhuang Jeo, Wu, Guanqing A novel gene encoding a TIG multiple domain protein is a positional candidate for autosomal recessive polycystic kidney disease Genomics 2002. 80:96-104

» Pummer, S, Dantzler, W H, Lien, Y H, Moeckel, G W, V??lker, K, Silbernagl, S Reabsorption of betaine in Henle''s loops of rat kidney in vivo Am J Physiol Renal Physiol 2000. 278:F434-9

» Stefan Pummer, William H. Danzler, Y.H.H. Lien, Gilbert Moeckel, Katharina Voelker and Stefan Silbernagl Reabsorption of betaine in Henle's loops of rat kidney in vivo American Journal of Physiology 2000. 278:F434-F439

» Gilbert W. Moeckel, Li-Wen Lai, Walter G. Guder, H.Moo Kwon and Yeong Hau H. Lien Kinetics and osmoregulation of Na- and Cl-dependent betaine transporter in rat renal medulla American Journal of Physiology 1997. 272:F100-106

» Gilbert W. Moeckel and Yeong Hau H Lien Distribution of de novo synthesized betaine in rat kidney:role of renal synthesis on medullary betaine accumulation American Journal of Physiology 1997. 272:F94-F99

» L-W Lai, GW Moeckel and YHH Lien Kidney-targeted liposome-mediated gene transfer in mice Gene Therapy 1997. 4:426-431

» Lai, L W, Moeckel, G W, Lien, Y H Kidney-targeted liposome-mediated gene transfer in mice Gene Ther 1997. 4:426-31

» Moeckel, G W, Lai, L W, Guder, W G, Kwon, H M, Lien, Y H Kinetics and osmoregulation of Na(+)-and Cl(-)-dependent betaine transporter in rat renal medulla Am J Physiol 1997. 272:F100-6

» Moeckel, G W, Lien, Y H Distribution of de novo synthesized betaine in rat kidney: role of renal synthesis on medullary betaine accumulation Am J Physiol 1997. 272:F94-9

» Gilbert W. Moeckel and Yeong Hau H. Lien Bicarbonate dependency of betaine synthesis in cultured LLC-PK1 cells American Journal of Physiology 1994. 266:F512-515

» Gilbert W. Moeckel, Juergen Hallbach and Walter Guder Purification of human and rat kidney aldose reductase Enzyme Protein 1994. 48:45-50

» Moeckel, G W, Lien, Y H Bicarbonate dependency of betaine synthesis in cultured LLC-PK1 cells Am J Physiol 1994. 266:F512-5

» Moeckel, G, Dasser, H G, Chen, T J, Schmolke, M, Guder, W G Bicarbonate-dependent betaine synthesis in rat kidney Contrib Nephrol 1994. 110:46-53

» Moeckel, G, Hallbach, J, Guder, W G Purification of human and rat kidney aldose reductase Enzyme Protein 1994. 48:45-50