Amrik Sahota, PhD, FACB, FACMG, FIBiol, FRCPath

My research is focused on the molecular pathology of inherited urinary tract stone disease. My colleagues and I have characterized the molecular bases of adenine phosphoribosyltransferse (APRT) deficiency in the vast majority of Caucasian patients with this disorder and I'm the senior author of the chapter on APRT deficiency in the Metabolic and Molecular Bases of Inherited Disease, the leading treatise in this field. APRT deficiency leads to 2,8-dihydroxyadenine (DHA) urolithiasis. We generated Aprt knockout mice and evaluated the effects of allopurinol therapy on DHA urolithiasis in these mice. The effects of various modifiers of stone disease, such as osteopontin (OPN) were studied in Aprt/Opn double knockout mice. We also generated Aprt/Hprt double knockout mice in relation to studies on the Lesch-Nyhan syndrome. To better understand the relationship between stone type and pathology, we developed a knockout mouse model for cystinuria by disrupting the Slc3a1 gene. Cystinuria is the most common inherited stone disease in children. Slc3a1 knockout excrete cystine and dibasic amino acids in the urine and male mice are more severely affected than females, which is consistent with observations in cystinuria patients. I'm a co-investigator on several NIH grants and contracts (see below). I'm a member of the Rare Kidney Stone Consortium (RKSC), a NIH-funded project on four single gene disorders of urolithiasis, including APRT deficiency and cystinuria. I received two-year funding from the RKSC to evaluate a new approach to cystinuria therapy using cystine mimics that inhibit cystine crystal growth. We're doing this work in collaboration with Dr. Michael Ward (Department of Chemistry, NYU), who pioneered the crystal inhibition approach, and Dr. David Goldfarb (Nephrology Section, NYU School of Medicine), who is the PI on the cystinuria component of RKSC and directs a clinic with over 50 patients with cystinuria. To expand the drug development work, we have recruited Drs. Brian Buckley, Kenneth Reuhl, and Tony Kong (Rutgers School of Pharmacy) who are experts in drug pharmacology and toxicology. We have also recruited Dr. Elaine Holmes and Mr. Matthew Lewis (Imperial College London). Dr. Holmes is an expert on systems biology approaches to understanding physiological and pathological processes and Mr. Lewis manages the LC-MS metabonomics facility; he's also a member of the RKSC and President of the International Cystinuria Foundation, the patient advocacy group for this disease. As part of the Rutgers University Cell and DNA Repository, we provide logistical and technical support for laboratories engaged in the search for genes for complex human diseases. In the Molecular Pathology Laboratory (Robert Wood Johnson University Hospital), we develop and implement into clinical practice molecular diagnostic assays for a variety of hematologic, infectious, and genetic diseases.

Selected Peer Reviewed Publications

1. Evan AP, Bledsoe SB, Connors BA, Deng L, Liang L, Shao C, Fineberg N, Grynpass MD, Stambrook PJ, Sahota A, Tischfield JA (2001). Sequential analysis of kidney stone disease in the Aprt knockout mouse. Kidney Int 60: 910-923. PMID: 11532086.
   
2. Vernon, HJ, Osborne C, Tzortzaki EG, Yang M, Rittling SR, Denhardt DT, Buyske S, Bledsoe SB, Evan AP, Fairbanks L, Simmonds HA, Tischfield JA, Sahota A (2005). Aprt/Opn double knockout mice: Osteopontin is a modifier of kidney stone disease severity. Kidney Int 68: 938-947. PMID: 16105024.
   
3. Liang L, Chen J, Vittal R, Selvanayagam ZE, McAteer JA, Deng L, Tischfield JA, Chin K-V, Sahota A (2006). Expression profiling of crystal-induced injury in human kidney epithelial cells. Nephron Physiol 103: 53-62. PMID: 16374038.
4. Chen Y, Capizzi S, Yang M,, Deng L, Bledsoe SB, Evan AP, Tischfield JA, Sahota A (2010). 2,8-Dihydroxyadenine nephrolithiasis induces developmental stage-specific alterations in gene expression in mouse kidney. Urology 75: 914-922. PMCID: PMC3177599.
5. Ercolani M, Sahota A, Schuler C, Yang M, Evan AP, Reimer D, Barone JG, Tischfield JA, Levin RM (2010). Bladder outlet obstruction in male cystinuria mice. Int Urol Nephrol 42: 57-63. PMCID: PMC3171145.

Additional relevant publications

6. Engle SJ, Stockelman MG, Chen J, Boivin G, Yum M-N, Davies PM, Ying MY, Sahota A, Simmonds HA, Stambrook PJ, Tischfield JA (1996). Adenine phosphoribosyltransferase-deficient mice develop 2,8-dihydroxyadenine nephrolithiasis. Proc Natl Acad Sci USA 93: 5307-5310. PMCID: PMC39241.
7. Engle SJ, Womer DE, Davies PM, Boivin G, Sahota A, Simmonds HA, Stambrook PJ, Tischfield JA (1996). HPRT-APRT deficient mice are not a model for Lesch-Nyhan syndrome. Hum Molec Genet 5: 1607-1610. PMID: 8894695
8. Stockelman M, Lorenz JN, Smith FN, Boivin GP, Sahota A, Tischfield JA, Stambrook PJ (1998). Chronic renal failure in a mouse model of human adenine phosphoribosyltransferase deficiency. Am J Physiol 275: F154-163. PMID: 9689017.
9. Wang L, Ou X, Sebesta I, Vondrak K, Krijt J, Elleder M, Poupetova H, Ledvinova J, Zeman J, Simmonds HA, Tischfield JA, Sahota A (1999). Combined adenine phosphoribosyltransferase and N-acetylgalactosamine-6-sulfate sulfatase deficiency. Molec Genet Metab 68: 78-85. PMID: 10479485.
10. Wang L, Raikwar N, Deng L, Yang M, Liang L, Shao C, Evan AP, Stambrook PJ, Sahota A, Tischfield JA (2000). Altered gene expression in kidneys of mice with 2,8-dihydroxyadenine nephrolithiasis. Kidney Int 58: 528-536. PMID: 10916076.
11. Wang L, Raikwar N, Deng L, Yang M, Liang L, Shao C, Evan AP, Stambrook PJ, Sahota A, Tischfield JA (2000). Altered gene expression in kidneys of mice with 2,8-dihydroxyadenine nephrolithiasis. Kidney Int 58: 528-536. PMID: 10916076.
12. Wang L, Raikwar N, Yang M, Deng L, McAteer JA, Stambrook PJ, Sahota A, Tischfield JA (2002). Induction of α-catenin, integrin α3, integrin β6, and PDGF-B by 2,8-dihydroxyadenine crystals in cultured kidney epithelial cells. Exp Nephrol 10: 365-373. PMID: 12381921.
13. Tzortzaki EG, Glass D, Yang M, Evan AP, Bledsoe SB, Stambrook PJ, Sahota A, Tischfield JA (2002). Gender- and age-dependent changes in kidney androgen protein mRNA expression in a knockout mouse model for nephrolithiasis. J Histochem Cytochem 50: 1663-1669. PMID: 12486089.
14. Tzortzaki EG, Yang M, Glass D, Deng L, Evan AP, Bledsoe SB, Stambrook PJ, Sahota A, Tischfield JA (2003). Impaired expression of an organic cation transporter, IMPT1, in a knockout mouse model for kidney stone disease. Urol Res 31: 257-261. PMID: 12856169.
15. Tzortzaki EG, Tischfield JA, Sahota A, Siafakas NM, Gordon MK, Gerecke DR (2003). Expression of FACIT collagens XII and XIV during bleomycin-induced pulmonary fibrosis in mice. Anat Rec 275A: 1073-1080. PMID: 14613307.