Center for Matrix Biology - Vanderbilt University and Medical Center

Jamshid Khoshnoodi, Ph.D.
Assistant Professor in the Department of Medicine

	Office Address:	384A PRB
	Mailing Address:	2220 Pierce Avenue, 383 Preston Research Building 384A PRB Nashville, TN 37232-2372
	Lab address:	Office 349A PRB
	Phone:	615-936-8576
		email

Secondary appointment in the Biochemistry department.

Research Summary

In diabetes, modification of vascular basement membrane proteins is one of the major causes of cellular and microvascular dysfunction which leads to diabetic complications, such as diabetic nephropathy, neuropathy, retinopathy and cardiovascular diseases. Basement Membranes are thin layers of highly specialized extracellular matrix glycoproteins and proteoglycans that directly regulate the behavior and functions of cells, tissues and organs. Molecular networks of basement membranes are formed through complex and highly specialized inter- and intramolecular interactions of basement membrane components such as collagen IV, laminin, nidogen and heparan sulfate proteoglycans.

Many genetic and acquired diseases are a direct consequence of mutations or modifications of BM molecules. For example, in Alport Syndrome, genetic mutations in certain collagen IV genes results in the alteration of glomerular basement membrane (GBM) network which ultimately leads to renal dysfunction. Modifications of the GBM components in diseases such as diabetes can also lead to renal function in Diabetic Nephropathy (DN), the most life-threatening complication in patients with diabetes mellitus.

Using proteomics technologies as discovery platforms, we are currently investigating the global changes in the serum and glomerular proteomes of a diabetic mouse model for type 2 diabetes (db/db). One of the immediate goals of the study is to identify novel biomarkers for detection of early onset of diabetic nephropathy. Using the above approach, several serum proteins have been identified and further investigation is underway to characterize the role of these proteins in the development of diabetic kidney disease.

Another research project is focused on the molecular assembly and interaction of Collagen XIX and its role in the formation and assembly of basement membranes.

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Associated initiative(s):

Biomaterials

Diabetic Complications

Fibrosis

Career opportunities:
None currently available

Selected Publications

» Shimizu, M, Khoshnoodi, J, Akimoto, Y, Kawakami, H, Hirano, H, Higashihara, E, Hosoyamada, M, Sekine, Y, Kurayama, R, Kurayama, H, Joh, K, Hirabayashi, J, Kasai, K, Tryggvason, K, Ito, N, Yan, K. Expression of Galectin-1, a New Component of Slit Diaphragm, is Altered in Minimal Change Nephrotic Syndrome Laboratory Investigation 2008 [Epub ahead of print]. :

» Khoshnoodi, J, Pedchenko, V, Hudson, BG Mammalian collagen IV Microsc Res Tech 2008. 71:357-70

» Khoshnoodi, J, Hill, S, Tryggvason, K, Hudson, B, Friedman, DB Identification of N-linked glycosylation sites in human nephrin using mass spectrometry J Mass Spectrom 2007. 42:370-9

» Nakajo, A, Khoshnoodi, J, Takenaka, H, Hagiwara, E, Watanabe, T, Kawakami, H, Kurayama, R, Sekine, Y, Bessho, F, Takahashi, S, Swiatecka-Urban, A, Tryggvason, K, Yan, K Mizoribine corrects defective nephrin biogenesis by restoring intracellular energy balance J Am Soc Nephrol 2007. 18:2554-64

» Fujii, Y, Khoshnoodi, J, Takenaka, H, Hosoyamada, M, Nakajo, A, Bessho, F, Kudo, A, Takahashi, S, Arimura, Y, Yamada, A, Nagasawa, T, Ruotsalainen, V, Tryggvason, K, Lee, AS, Yan, K The effect of dexamethasone on defective nephrin transport caused by ER stress: a potential mechanism for the therapeutic action of glucocorticoids in the acquired glomerular diseases Kidney Int 2006. 69:1350-9

» Khoshnoodi, J, Cartailler, JP, Alvares, K, Veis, A, Hudson, BG Molecular recognition in the assembly of collagens: terminal noncollagenous domains are key recognition modules in the formation of triple helical protomers J Biol Chem 2006. 281:38117-21

» Khoshnoodi, J, Sigmundsson, K, Cartailler, JP, Bondar, O, Sundaramoorthy, M, Hudson, BG Mechanism of chain selection in the assembly of collagen IV: a prominent role for the alpha2 chain J Biol Chem 2006. 281:6058-69

» Ruotsalainen, Vesa, Reponen, Paula, Khoshnoodi, Jamshid, Kilpel??inen, Pekka, Tryggvason, Karl Monoclonal antibodies to human nephrin Hybrid Hybridomics 2004. 23:55-63

» Nishibori, Yukino, Liu, Li, Hosoyamada, Makoto, Endou, Hitoshi, Kudo, Akihiko, Takenaka, Hitoshi, Higashihara, Eiji, Bessho, Fumio, Takahashi, Shori, Kershaw, David, Ruotsalainen, Vesa, Tryggvason, Karl, Khoshnoodi, Jamshid, Yan, Kunimasa Disease-causing missense mutations in NPHS2 gene alter normal nephrin trafficking to the plasma membrane Kidney Int 2004. 66:1755-65

» Wartiovaara, Jorma, Ofverstedt, Lars-G??ran, Khoshnoodi, Jamshid, Zhang, Jingjing, M??kel??, Eetu, Sandin, Sara, Ruotsalainen, Vesa, Cheng, R Holland, Jalanko, Hannu, Skoglund, Ulf, Tryggvason, Karl Nephrin strands contribute to a porous slit diaphragm scaffold as revealed by electron tomography J Clin Invest 2004. 114:1475-83

» Khoshnoodi, Jamshid, Sigmundsson, Kristmundur, Ofverstedt, Lars-G??ran, Skoglund, Ulf, Obrink, Bj??rn, Wartiovaara, Jorma, Tryggvason, Karl Nephrin promotes cell-cell adhesion through homophilic interactions Am J Pathol 2003. 163:2337-46

» Yan, Kunimasa, Khoshnoodi, Jamshid, Ruotsalainen, Vesa, Tryggvason, Karl N-linked glycosylation is critical for the plasma membrane localization of nephrin J Am Soc Nephrol 2002. 13:1385-9

» Liu, L, Don??, S C, Khoshnoodi, J, Bertorello, A, Wartiovaara, J, Berggren, P O, Tryggvason, K Defective nephrin trafficking caused by missense mutations in the NPHS1 gene: insight into the mechanisms of congenital nephrotic syndrome Hum Mol Genet 2001. 10:2637-44

» Khoshnoodi, J, Tryggvason, K Congenital nephrotic syndromes Curr Opin Genet Dev 2001. 11:322-7

» Khoshnoodi, J, Tryggvason, K Unraveling the molecular make-up of the glomerular podocyte slit diaphragm Exp Nephrol 2001. 9:355-9

» Larsson, C T, Khoshnoodi, J, Ek, B, Rask, L, Larsson, H Molecular cloning and characterization of starch-branching enzyme II from potato Plant Mol Biol 1998. 37:505-11

» Khoshnoodi, J., Larsson, C-T. Larsson, H. and Rask, L Differential accumulation of Arabidopsis thaliana Sbe2.1 and Sbe2.2 transcripts in response to light Plant Science 1998. 135:183-193

» Khoshnoodi, J, Blennow, A, Ek, B, Rask, L, Larsson, H The multiple forms of starch-branching enzyme I in Solanum tuberosum Eur J Biochem 1996. 242:148-55

» Larsson CT, Hofvander P, Khoshnoodi, J., Ek B, Rask L, Larsson H Three isoforms of starch synthase and two isoforms of branching enzyme are present in potato tuber starch Plant Science 1996. 117:9-16

» Khoshnoodi, J, Ek, B, Rask, L, Larsson, H Characterization of the 97 and 103 kDa forms of starch branching enzyme from potato tubers FEBS Lett 1993. 332:132-8