Samy L. Habib, M.S., Ph.D.Associate Professor
Alexandria University, Alex, Egypt and
Roswell Park Cancer Institute, Buffalo, NY, 1993
(210) 567- 3816
- Carcinogenesis in Diabetes - The project goal is to study the role of diabetes in the development of renal cell carcinoma. Patients with diabetes are at higher risk than the general population of developing cancer of the urinary tract, liver, biliary tract, pancreas, colon, endometrium and kidney. The mechanism (s) by which patients with diabetes are predisposed to cancer are not known.
- Mechanism of reducing renal tumorigenesis - Inhibition of mTOR by rapamycin is an important approach in cancer therapy. In early clinical trials, tuberous sclerosis complex (TSC)-related kidney tumours were found to regress following rapamycin treatment. Loss of function of the DNA repair OGG1 enzyme has a major role in multistep carcinogenesis of the kidney and other organs. The goal of this project is to find novel drugs combination to treat kidney tumor.
- Mutations of OGG1 in Diabetic and Cancer Patients - Mutations in the DNA repair gene OGG1 is increased in several tumor tissue including kidney. The project goal is to measure the levels of oxidative DNA damage and identify the mutations in OGG1 gene in diabetic and cancer patients.
- Role of Tuberin in Renal Hypertrophy and Fibrosis - Renal hypertrophy, matrix protein accumulation and tubulointerstitial fibrosis are major pathological features of diabetic nephropathy (DN) that eventuate in renal failure. Hyperglycemia and high concentration of glucose increase matrix protein expression but the pathogenic mechanisms are not fully understood. The project goal is to determine the mechanism by which high glucose regulates tuberin and downstream signaling pathways to enhance extracellular matrix protein accumulation in renal proximal tubular epithelial cells.
- Role of tuberin/mTOR pathway in apoptosis - Apoptosis contributes to the development of diabetic nephropathy but the mechanism by which high glucose (HG) induces apoptosis is not fully understood. The goal of this project is to investigate the role of tuberin/mTOR pathway in apoptosis in diabetes and in cultured proximal tubular epithelial cells exposed to HG.
- Screening of diabetic patients for cancer - Kidney cancer is one of the ten leading sites of cancer incidence in Texas; however, the association of DM and RCC histology has not been explored. The goal of this project is to investigate the association between diabetes and renal cancer. All RCC cases at our center from 1994 to 2010 will be analyzed with relation to history of diabetes, diabetic laboratory parameters gender, ethnicity, age and tumor morphology.
- DNA damage using HPLC-EC (detection limit of DNA damage up to 10 fenta-mole) as well as specific detection of DNA damage by immunohistochemistry.
- DNA repair activity assay
- Cell apoptosis assays including cell signals, Hoechst staining, Annexin assay
- Cell hypertrophy
- Cell proliferation
- Promoter reporter assay
- RNA interference
- Nuclear and Mitochondrial fractionation
- Rat hepatectomy and pancreatectomy
Habib SL, Bhandari BK, Sadek N, Abboud-Werner SL, Abboud HE. (2010) Novel mechanism of regulation of the DNA repair enzyme OGG1 in tuberin-deficient cells. Carcinogenesis. 2010 Nov;31(11):2022-30.
Lai KP, Leong WF, Chau JF, Jia D, Zeng L, Liu H, He L, Hao A, Zhang H, Meek D, Velagapudi C, Habib SL, Li B. (2010) S6K1 is a multifaceted regulator of Mdm2 that connects nutrient status and DNA damage response. EMBO J. 2010 Sep 1;29(17):2994-3006.
Habib SL, Kasinath BS, Arya RR, Vexler S, Velagapudi C. (2010) Novel mechanism of reducing tumourigenesis: upregulation of the DNA repair enzyme OGG1 by rapamycin-mediated AMPK activation and mTOR inhibition. Eur J Cancer. 2010 Oct;46(15):2806-20.
Mahimainathan L, Ghosh-Choudhury N, Venkatesan B, Das F, Mandal CC, Dey N, Habib SL, Kasinath BS, Abboud HE, Ghosh Choudhury G. (2009) TSC2 deficiency increases PTEN via HIF1alpha. J Biol Chem. 2009 Oct 9;284(41):27790-8.