Raymond Harris

Personal Information
Title Professor
Expertise Nephropathy
Institution Vanderbilt University
Data Summary
TypeCount
Grants/SubContracts 2
Progress Reports 7
Presentations 3
Publications 30
Protocols 2
Committees 3
Experiments 0
Strains 4
Models 4

SubContract(s)


An outbred mouse strain to study diabetic nephropathy
To date, the AMDCC has nearly exclusively characterized inbred laboratory mice strains to study the development diabetes nephropathy. These studies support the influence of genetic risk factors as contributing to diabetic nephropathy in these inbred lines. In this regard some strains, like DBA2 develop more robust nephropathy than C57BL/6. Nevertheless, the complexity the genomes of inbred mouse strain are drastically reduced, as compared to the genetic complexity of outbred human populations. Inbred mice are homozygous at all loci; whereas in outbred populations, loci allowed to exist in both heterozygous and homozygous states . Furthermore during the process of brother-sister mating used to derive inbred mouse strains, any polymorphisms that either decrease fecundity or are lethal when homozygous, are lost. If similar mutations contribute, in a dominant or semi-dominant fashion, to human diabetic nephropathy, this variability would never be seen in inbred mouse models. In this regard, one of the specific suggestions of the AMDCC External Advisory Committee was to consider utilizing outbred mouse strains to investigate genetic predisposition for development of diabetic complications. We propose to characterize the progression of nephropathy in diabetic outbred CD-1 mice. A recent study has reported that CD-1 mice develop significant nephropathy in a streptozotocin-induced model of diabetes. This study reported that mice made diabetic by a high dose (single injection) streptozotocin protocol develop ESRD associated with prominent tubulointerstitial nephritis and fibrosis within 3 months and die because of diabetic complications by 6-7 months. In this regard, our own preliminary data in CD-1 mice indicate significant diversity in the levels of albuminuria (following STZ induced diabetes) among individual mice (see below). Such heterogeneity may indicate that outbred mice might more closely resemble the heterogeneity of human populations and might also provide the opportunity to capture dominant genes that contribute to increased albuminuria and diabetic nephropathy. For this reason, we propose to characterize the extent and heterogeneity of diabetic nephropathy in CD-1 mice and to begin to develop crosses for detecting dominant heritable traits predisposing to development and/or progression of diabetic nephropathy. Our first specific aim will be to characterize the variability of the development of nephropathy in the CD-1 strain. Our second specific aim is to to initiate a backcross of CD-1 mice with B6Akita mice, a strain resistant to development of diabetic nephropathy, in order to begin to identify potential dominant alleles that contribute to diabetic nephropathy.

Imaging Mass Spectroscopic Analysis of Human Diabetic Glomerulopathy
The spectrum of lesions in patients with diabetes who do not have classic or overt diabetic nephropathy is not established. Recently, there has been recognition that many patients with diabetes experience chronic kidney disease without significant albuminuria or evidence of other primary glomerulonephritis. Whether this injury is also attributable to diabetes or other underlying unrecognized injury processes is not established. The typical diabetic patient with nephropathy does not undergo renal biopsy. Current renal biopsies done in diabetic patients for clinical indications thus show a high incidence of disease superimposed on diabetes, such as IgA nephropathy, crescentic glomerulonephritis, proliferative glomerulonephritis, post-infectious glomerulonephritis, etc. Many show no other morphologic findings other than diabetic nephropathy, but diseases more advanced than predicted from the clinical data. We aim to use novel proteomic techniques to mine and phenotype diabetic nephropathy from existing archival renal biopsies, and prospectively to examine in tissues obtained from nephrectomies in diabetic and non-diabetic patients with or without nephropathy, and in autopsies. These approaches will allow us to map the spectrum of lesions that may be attributable to diabetes or to other unrecognized abnormalities in diabetic patients. These pilot studies will importantly interact with a companion pilot grant proposing to establish a pre-consenting cohort for tissue collection that will be linked to a synthetic derivative electronic medical record (BioVU). Validation of a detailed phenotype of existing diabetic nephropathy will allow detailed prospective mining of such samples that we plan to collect building on our expertise with BioVU. Our aims thus are as follows: 1) We aim to test the feasibility of examining the presence of proteins, metabolites, lipid derivatives in tissue, linked to the microenvironmental phenotype, by use of mass spectroscopy imaging and image fusion techniques. 2) We aim to link novel compounds identified linked to diabetes to detailed phenotypic analysis by light microscopy with morphometry and electron microscopy. Lay: We aim to use new techniques of mass spectroscopy to analyze the exact abnormalities present in kidney samples in patients with diabetes and kidney disease.


Progress Reports

Annual Reports

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Harris, Raymond (2007)
2007Annual Report
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Harris, Raymond (2008)
2008Annual Report
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Harris, Raymond (2009)
2009Annual Report
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Harris, Raymond (2010)
2010Annual Report
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Harris, Raymond (2011)
2011Annual Report
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 PublicationAltmetricsSubmitted ByPubMed IDStatus

Year: 2015; Items: 1

 
EGF receptor deletion in podocytes attenuates diabetic nephropathy.
Chen J, Chen JK, Harris RC
Journal of the American Society of Nephrology : JASN, 2015 (26), 1115 - 1125
25185988
Published

Year: 2014; Items: 2

 
24705402
Published
 
25371905
Published

Year: 2013; Items: 2

 
Identification of cross-species shared transcriptional networks of diabetic nephropathy in human and mouse glomeruli.
Hodgin JB, Nair V, Zhang H, Randolph A, Harris RC, Nelson RG, Weil EJ, Cavalcoli JD, Patel JM, Brosius FC, Kretzler M
Diabetes, 2013 (62), 299 - 308
23139354
Published
 
The best-laid plans.
Harris RC
American journal of physiology. Renal physiology, 2013 (304), F1086 - F1087
23269642
Published

Year: 2012; Items: 10

 
Role of blood pressure and the renin-angiotensin system in development of diabetic nephropathy (DN) in eNOS-/- db/db mice.
Zhang MZ, Wang S, Yang S, Yang H, Fan X, Takahashi T, Harris RC
American journal of physiology. Renal physiology, 2012 (302), F433 - F438
22114203
Published
 
Abnormalities in renal dopamine signaling and hypertension: the role of GRK4.
Harris RC
Current opinion in nephrology and hypertension, 2012 (21), 61 - 65
22123211
Published
 
Intrarenal dopamine modulates progressive angiotensin II-mediated renal injury.
Yang S, Yao B, Zhou Y, Yin H, Zhang MZ, Harris RC
American journal of physiology. Renal physiology, 2012 (302), F742 - F749
22169008
Published
 
Integrin a1/Akita double-knockout mice on a Balb/c background develop advanced features of human diabetic nephropathy.
Yu L, Su Y, Paueksakon P, Cheng H, Chen X, Wang H, Harris RC, Zent R, Pozzi A
Kidney international, 2012 (81), 1086 - 1097
22297672
Published
 
Generation of a conditional allele for the mouse endothelial nitric oxide synthase gene.
Jiang R, Wang S, Takahashi K, Fujita H, Fruci CR, Breyer MD, Harris RC, Takahashi T
Genesis (New York, N.Y. : 2000), 2012 (50), 685 - 692
22467476
Published
 
SOD1, but not SOD3, deficiency accelerates diabetic renal injury in C57BL/6-Ins2(Akita) diabetic mice.
Fujita H, Fujishima H, Takahashi K, Sato T, Shimizu T, Morii T, Shimizu T, Shirasawa T, Qi Z, Breyer MD, Harris RC, Yamada Y, Takahashi T
Metabolism: clinical and experimental, 2012 (61), 1714 - 1724
22632894
Published
 
Intrarenal dopamine inhibits progression of diabetic nephropathy.
Zhang MZ, Yao B, Yang S, Yang H, Wang S, Fan X, Yin H, Fogo AB, Moeckel GW, Harris RC
Diabetes, 2012 (61), 2575 - 2584
22688335
Published
 
Improvement of endothelial nitric oxide synthase activity retards the progression of diabetic nephropathy in db/db mice.
Cheng H, Wang H, Fan X, Paueksakon P, Harris RC
Kidney international, 2012 (82), 1176 - 1183
22785174
Published
 
Podocyte ACE2 protects against diabetic nephropathy.
Harris RC
Kidney international, 2012 (82), 255 - 256
22791320
Published
 
eNOS deficiency predisposes podocytes to injury in diabetes.
Yuen DA, Stead BE, Zhang Y, White KE, Kabir MG, Thai K, Advani SL, Connelly KA, Takano T, Zhu L, Cox AJ, Kelly DJ, Gibson IW, Takahashi T, Harris RC, Advani A
Journal of the American Society of Nephrology : JASN, 2012 (23), 1810 - 1823
22997257
Published

Year: 2011; Items: 2

 
Intrarenal dopamine deficiency leads to hypertension and decreased longevity in mice.
Zhang MZ, Yao B, Wang S, Fan X, Wu G, Yang H, Yin H, Yang S, Harris RC
The Journal of clinical investigation, 2011 (121), 2845 - 2854
21701066
Published
 
Podocyte COX-2 exacerbates diabetic nephropathy by increasing podocyte (pro)renin receptor expression.
Cheng H, Fan X, Moeckel GW, Harris RC
Journal of the American Society of Nephrology : JASN, 2011 (22), 1240 - 1251
21737546
Published

Year: 2009; Items: 4

 
Reduction of renal superoxide dismutase in progressive diabetic nephropathy.
Fujita H, Fujishima H, Chida S, Takahashi K, Qi Z, Kanetsuna Y, Breyer MD, Harris RC, Yamada Y, Takahashi T
Journal of the American Society of Nephrology : JASN, 2009 (20(6)), 1303 - 1313
19470681
Published
 
S6 kinase 1 knockout inhibits uninephrectomy- or diabetes-induced renal hypertrophy.
Chen JK, Chen J, Thomas G, Kozma SC, Harris RC
American journal of physiology. Renal physiology, 2009 (297), F585 - F593
19474189
Published
 
Distinct roles for basal and induced COX-2 in podocyte injury.
Cheng H, Fan X, Guan Y, Moeckel GW, Zent R, Harris RC
Journal of the American Society of Nephrology : JASN, 2009 (20), 1953 - 1962
19643929
Published
 
Mouse Models of Diabetic Nephropathy: A Midstream Analysis from the Diabetic Complications Consortium
Frank C. Brosius IIIa, Charles E. Alpersb, Erwin P. Bottingerc, Matthew D. Breyerd, ThomasM. Coffmane, Susan B. Gurleye, Raymond C. Harrisf, Masao Kakokig, Matthias Kretzler, Edward H. Leiterh, Moshe Levii, Richard A. McIndoej, Kumar Sharmak, Oliver Smithiesg, Katalin Susztakl, Nobuyuki Takahashig, Takamune Takahashif
Journal of the American Society of Nephrology : JASN, 2009 (20(12)), 2503 - 2512
19729434
Published

Year: 2008; Items: 2

 
Insight into the genetics of diabetic nephropathy through the study of mice.
Breyer MD, Qi Z, Tchekneva EE, Harris RC
Current opinion in nephrology and hypertension, 2008 (17(1)), 82 - 86
18090675
Published
 
Single amino acid substitution in aquaporin 11 causes renal failure.
Tchekneva EE, Khuchua Z, Davis LS, Kadkina V, Dunn SR, Bachman S, Ishibashi K, Rinchik EM, Harris RC, Dikov MM, Breyer MD
Journal of the American Society of Nephrology : JASN, 2008 (19(10)), 1955 - 1964
18701606
Published

Year: 2007; Items: 3

 
Genetics of diabetic nephropathy: lessons from mice.
Breyer MD, Tchekneva E, Qi Z, Takahashi T, Fogo AB, Zhao HJ, Harris RC
Seminars in nephrology, 2007 (27)
17418691
Published
 
Deficiency of endothelial nitric-oxide synthase confers susceptibility to diabetic nephropathy in nephropathy-resistant inbred mice.
Kanetsuna Y, Takahashi K, Nagata M, Gannon MA, Breyer MD, Harris RC, Takahashi T
The American journal of pathology, 2007 (170), 1473 - 1484
17456755
Published
 
Examining diabetic nephropathy through the lens of mouse genetics.
Breyer MD, Tchekneva E, Qi Z, Takahashi T, Fogo AB, Harris RC
Current diabetes reports, 2007 (7(6)), 459 - 466
18255011
Published

Year: 2006; Items: 1

 
Nitric oxide stimulates cyclooxygenase-2 in cultured cTAL cells through a p38-dependent pathway.
Cheng HF, Zhang MZ, Harris RC
American journal of physiology. Renal physiology, 2006 (290), F1391 - F1397
16380459
Published

Year: 2005; Items: 3

 
Mouse Models of Diabetic Nephropathy
MATTHEW D. BREYER, ERWIN BÖTTINGER, FRANK C. BROSIUS, III, THOMAS M. COFFMAN, RAYMOND C. HARRIS, CHARLES W. HEILIG, AND KUMAR SHARMA (FOR THE AMDCC)
Journal of the American Society of Nephrology : JASN, 2005 (16), 27 - 45
15563560
Published
 
Diabetic nephropathy: of mice and men.
Breyer MD, Böttinger E, Brosius FC, Coffman TM, Fogo A, Harris RC, Heilig CW, Sharma K
Advances in chronic kidney disease, 2005 (12(2)), 128 - 145
15822049
Published
 
Expression of mediators of renal injury in the remnant kidney of ROP mice is attenuated by cyclooxygenase-2 inhibition.
Cheng H, Zhang M, Moeckel GW, Zhao Y, Wang S, Qi Z, Breyer MD, Harris RC
Nephron. Experimental nephrology, 2005 (101), e75 - 85
15995341
Published

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Harris, Raymond (2009)
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No experiments found.