DeWolf Laboratory
Basic Research
The basic component of my own research deals with biochemical characterization of a stem cell antigen that we originally described in 1992 (Schopperle W, Armant R, DeWolf WC: Purification of a tumor specific PNA-binding glycoprotein, gp200, from a human embryonal carcinoma cell line. Arch Biochem Biophys 1992;298:538). We were the first to sequence the molecule and it has been found to be identical to a protein called podocalyxin (also Gp200, TRA1-60, and GCTM-2) (Schopperle WM, Kershaw DB, DeWolf WC. Human embryonal carcinoma tumor antigen Gp200/GCTM2, is Podocalyxin. Biochem Biophys Res Commun 2003;300:295-300). This molecule is a 528 amino acid transmembrane protein that is heavily glycosylated and contains a single putative transmembrane domain. Podocalyxin has a large extracellular region containing a mucin and globular domain and a small cytoplasmic domain with a PDZ-binding motif. Podocalyxin was originally identified and cloned from podocytes, the blood-filtering cells of the body, where it has been shown to have putative function as a protein anchoring membrane protein that forms complexes with other proteins through its cytoplasmic PDZ-binding motif. This podocalyxin complex is critical for proper podocyte function. We are studying with what podocalyxin is interacting in embryonal carcinoma cells. Protein sequencing data reveal that glucose-3 transporter, the testis and brain-specific glucose transporter, copurifies with podocalyxin in purified protein fractions from embryonal carcinoma stem cells. Immuno-precipitation experiments with antiglucose-3 transporter and podocalyxin antibody confirm a stable complex exists in detergent extracted protein lysates. Podocalyxin may be functioning as an anchoring protein for this plasma membrane glucose transporter in stem cells. Current studies are underway to determine if podocalyxin and the transporter are interacting directly or if other proteins interacting through the PDZ-binding motif are tethering podocalyxin to the transporter, and to explore if there is any critical function for this complex in pleuripotent stem cells.
Clinical Research
Clinical research within the Division of Urology is very active. Included is an analysis of a ten-year experience of patients who have undergone radical prostatectomy. Their case histories with data have been put into a computerized retrieval system for data analysis. Thus far, six manuscripts have been generated and four accepted for publication.
| 2004- |
A phase 3, parallel group, randomized, double-blind, placebo-controlled multicenter trial to investigate the efficacy, tolerability, and safety of fesoterodine sustained release in subjects with overactive bladder syndrome. Funding: Schwarz Pharma. Clinical Research. Study of duloxetine in women of different demographic characteristics and co-morbidities with stress urinary incontinence: evaluation of efficacy and safety. Funding: Eli Lilly. Clinical research.
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| 2001-2002 |
A phase II, double-blind, randomized, parallel group multi-center study of Flomax capsules, 0.4 mg vs. placebo in male patients with acute urinary retention related to benign prostatic hyperplasia. Anurag K. Das, MD, PI. Funding: Boehringer-Ingelheim 527.26. Clinical research. |
| 2001-2002 |
An eight-week, double-blind, randomized, parallel group multi-center study of Flomax capsules, 0.4 mg vs. placebo in female patients with lower urinary tract symptoms (LUTS) . Anurag K. Das, MD, PI. Phase II. Funding: Boehringer-Ingelheim 527.25. Clinical research. |
| 2001-2002 |
The safety, local tolerability and risk/ benefit of oxybutynin transvaginal rings in women with a history of overactive bladder. Anurag K. Das, MD, PI. Phase II. Funding: FEI Incorporated. Clinical research. |
| 2002-2003 |
A randomized double-blind, placebo-controlled dose finding study to evaluate the effects of partial alpha 1a/1l adrenoreceptor agonist Ro 115-1240 in women with stress urinary incontinence or mixed urinary incontinence. Anurag K. Das, MD, PI. Funding: Roche Bioscience. Clinical research. |
| 2002 |
A double-blind, placebo-controlled, randomized US study to evaluate the effect of tolterodine prolonged release on nocturia in patients with symptoms of overactive bladder (OAB). Anurag K. Das, MD, PI. Funding: Pharmacia. Clinical research. |
