|Life Sciences Building Rutgers University 145 Bevier Road Piscataway, NJ, 08854|
I have interests in three major areas: urolithiasis research, biorepository operations, and molecular diagnostics.
My research is focused on the molecular pathology of inherited urinary tract stone disease. This work is done in collaboration with Dr. Jay Tischfield, Department of Genetics. My colleagues and I have characterized the molecular bases of adenine phosphoribosyltransferse (APRT) deficiency in the majority of Caucasian patients with this disorder and we are authors 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 interaction of crystals with renal epithelial cells is an important event in the initiation of cellular injury. We therefore developed a cell culture system for studying the effects of DHA crystals on human renal epithelial cells. We identified a subset of genes whose expression is significantly altered in Aprt-deficient mice or in cells exposed to DHA crystals. These genes encode proteins involved in many biological processes, including tissue calcification, fibrosis, and inflammation.
We also developed an Aprt/Opn double knockout (DKO) mouse to study the effects of osteopontin (OPN) on stone disease. OPN has multiple cellular functions, including its effect as a modifier of stone disease. We demonstrated that OPN is a major inhibitor of DHA crystal deposition and inflammation in male mice.
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.
We're evaluating 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 (NYU), who pioneered the crystal inhibition approach; Dr. David Goldfarb (NYU School of Medicine), who directs a clinic with a large number of patients with cystinuria; and Dr. Elaine Holmes and Mr. Matthew Lewis (Imperial College London, UK), who are experts on systems biology approaches to understanding pathological and pharmacological processes.
At the Rutgers University Cell and DNA Repository (RUCDR), I oversee or contribute to a number of activities, including: (i) provision of educational and safety training programs for staff; (ii) verification of pedigree relationships; (iii) development of molecular diagnostic assays for research purposes; (iv) resolution of cell line or DNA quality control issues; and (v) compliance with regulatory guidelines. Two of my RUCDR colleagues (Dr. Jay Tischfield and Andrew Brooks) and I are authors of the chapter entitled "Preparing DNA from Mammalian Sources" in Genetic Variation: A Laboratory Manual (Weiner MP et al, Eds). RUCDR is one of a small number of biorespositories that is accredited by the College of American Pathologists.
In the Molecular Pathology Laboratory (located at Robert Wood Johnson University Hospital, New Brunswick, NJ), we develop and implement into clinical practice molecular diagnostic tests for a variety of hematologic, infectious, and genetic diseases.
Selected publications (from over 90)
1. Evans RM, Emsley CL, Gao S, Sahota A, Hall KS, Farlow MR, Hendrie H (2000). Serum cholesterol, APOE genotype, and the risk of Alzheimer's disease: a population-based study of African Americans. Neurology. 54: 240-242.
2. Sahota A, Gao S, Hayes J, Jindal RM (2000). Microchimerism and rejection: A meta-analysis. Clin Transplant 14: 346-351.
3. 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.
4. Deng L, Yang M, Fründ S, Wessel T, De Abreu RA, Tischfield JA, Sahota A (2001). Dihydroxyadenine urolithiasis in a patient with considerable residual adenine phosphoribosyltransferase activity in cell extracts but with mutations in both copies of APRT. Mol Genet Metab 72: 260-264.
5. 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.
6. Wang L, Raikwar N, Yang M, Deng L, McAteer JA, Stambrook PJ, Sahota A, Tischfield JA (2002). Induction of ?-catenin, integrin ?3, integrin ?6, and PDGF-B by 2,8-dihydroxyadenine crystals in cultured kidney epithelial cells. Exp Nephrol 10: 365-373.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. Mackinnon AC Jr, Wang YL, Sahota A, Yeung CC, Weck KE (2012). Certification in Molecular Pathology in the United States: An update from the Association for Molecular Pathology Training and Education Committee. J Mol Diagn 14: 541-549.
15. Edvardsson VO, Palsson R, Sahota A (2012). Adenine phosphoribosyltransferase deficiency. In: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-. 2012 Aug 30.
Books and book chapters
1. Taylor MW, Sahota A (1989). Cellular resistance to adenine analogues. In "Drug resistance in mammalian cells (Vol 1): Antimetabolites and cytotoxic analogs" (Gupta RS, Ed), CRC Press, Boca Raton, Florida, pp 111-124.
2. Sahota A, Taylor MW (Eds) (1994). Advances in experimental medicine and biology (Vol 370), Plenum Press, New York.
3. Simmonds HA, Sahota AS, Van Acker KJ (1995). Adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadenine lithiasis. In "The metabolic and molecular bases of inherited disease", 7th ed (Scriver CR et al, Eds), McGraw-Hill, New York, pp 1029-1044. Also 6th ed (1989) and CD-ROM ed (1997).
4. Sahota AS, Tischfield JA, Kamatani N, Simmonds HA (2001). Adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadenine lithiasis. In "The metabolic and molecular bases of inherited disease", 8th ed (Scriver CR et al, Eds), McGraw-Hill, New York, pp 2571-2584.
5. Sahota A (2005). The APRT gene. In "Caring for patients with adenine phosphoribosyltransferase deficiency" (Cameron JS, Ed). Chapter in booklet published by the Purine Metabolic Patients Association, London, UK.
6. Sahota A, Brooks AI, Tischfield JA (2007). Preparing DNA from mammalian sources. In: Genetic Variation: A Laboratory Manual (Weiner MP, Gabriel SB, Stephens JC, Eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp 103-106.
7. Sahota A, Brooks AI, Tischfield JA (2007). Preparing DNA from cell pellets. In: Genetic Variation: A Laboratory Manual (Weiner MP, Gabriel SB, Stephens JC, Eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp 107-109.
8. Sahota A, Brooks AI, Tischfield JA, King IB (2007). Preparing genomic DNA from whole blood: Small- and mid-scale extraction. In: Genetic Variation: A Laboratory Manual (Weiner MP, Gabriel SB, Stephens JC, Eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp 120-123.
9. Sahota A, Brooks AI, Tischfield JA (2007). Preparing DNA from blood: Large-scale extraction. In: Genetic Variation: A Laboratory Manual (Weiner MP, Gabriel SB, Stephens JC, Eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp 124-128.
10. Sahota A, Brooks AI, Tischfield JA (2007). Preparing DNA from saliva. In: Genetic Variation: A Laboratory Manual (Weiner MP, Gabriel SB, Stephens JC, Eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp 129-130.