Ronald Moore
Contact
Professor, Faculty of Medicine & Dentistry - Surgery Dept
- rbmoore@ualberta.ca
- Phone
- (780) 407-6330
- Address
-
2D2 WMC Mackenzie Health Science Centre
8440 - 112 StEdmonton ABT6G 2B7
Overview
Area of Study / Keywords
About
Educational Background:Research
PDT
We have investigated the mechanism of action of Porphyrin (5-ALA/PpIX, Photofrin and BPD-MA) and Hypocrellin mediated PDT and photodetection (PD). With these
Further research accomplishments related to preclinical PDT investigations have been the development of a light delivery apparatus that allows tissue characterization and real time dosimetry for intra arterial photosensitization. This has lead to a patent (Tulip J, Moore RB, Dickey D: Switched PDT Apparatus and Treatment Methods. US Patent # 60/464/656) and commercialization through Altachem Pharma Ltd. To accomplish this, modeling of light dosimetry was carried out in phantoms, our rat prostate tumor and dog models, and human cystoprostatectomy specimens. Key to this was the development of a novel approach for characterizing tissue using angular radiance (Barajas et al. Phys. Med. Biol. 42(9):1675-1687, 1997). We found that an interstitial light source implanted in tissue produces an angular radiance (light flux at a specific angle, W/m2 sr) that becomes progressively isotropic as a function of distance. The anisotropy in the angular radiance as a function of distance is sensitive to variations in the optical coefficients, such that measurements of angular radiance yield information about these coefficients. With this finding, we have solved the P-3 approximation which allows us to generate real-time 3 dimensional (3-D) isodose plots (Dickey et.al. Phys Med Biol 46:2359-2370, 2001; SPIE Proceedings J.B.O. 4156:181-88, 2000). With this ability to characterize tissue in 3-D (Dickey et al., Phys. Med.Biol., in press) we further refined our light delivery apparatus to switch between optical sources and detectors complete with spectrometer to monitor drug levels (Dickey et.al., Journal of Biomedical Optics, in press). These refinements have resulted in less toxicity and greater efficacy in our animal models. In the Dunning Prostate model we have shown increased efficacy with both BPD and HBD using the switched light apparatus (Xiao Z,etal. Abst. Can. J. Urol. CUA Annual Meeting, June, 2003). In the dog model we have shown selective intra arterial delivery of HBD and BPD with therapeutic ratios of >100:1 between prostate and surrounding tissue (Moore RB, etal. Abst. Can. J. Urol. CUA Annual Meeting, June, 2003).
Tumor Models
Other significant research has included the development and characterization of a transplantable orthotopic rat bladder
Using the same methodologies we also developed a transplantable orthotopic model of human MGHU-3 TCC xenografted into nude rats. This
We have also developed an in-vitro bladder tumor model and characterized it for testing topical drug delivery. This model has been used to test targeted drug delivery for several novel intravesical therapies (Selective Reovirus Killing of Bladder Cancer in a Co-Culture Spheroid Model. Virus Research 93:1-12, 2003; Selective Cytotoxicity of Gemcitabine in Bladder Cancer Cell Lines. Anticancer Drugs 13(6):557-66, 2002; and Immunoliposomal Targeting of Transitional Cell Carcinoma with 48-127 mAb. Manuscript under revision). This model system has supported our ex-vivo studies on human Equilibrative Nucleoside Transporter 1 (hENT1) protein in transitional cell carcinoma (Mulder KE, et.al.Urol., in press), and intravesical Reovirus ( Hanel EG, et. al. J. Urol. In press). These studies have lead to proposing separate clinical trials with intravesical gemcitabine and reovirus.
Reovirus
Based on the pioneering work of
Molecular Modifiers
In collaboration with Drs. Charlie Hao, Wilson Roa and Martin Gleave we have been investigating TRAIL and antisense oligonucleotides (
Transplantation
In the field of transplantation we are investigating reverse oncologic strategies to make differentiated cells proliferate in a controlled fashion. We have investigated and shown that senescence, as evident by telomere shortening, may have an important role in the longevity of renal allografts (J. Am. Soc. Nephol. 11:444-453). This finding has generated a great deal of interest in molecular strategies to over come this replicative limitation to chronic low-grade immunologic injury. We are currently studying nonviral means of gene transfection (liposomal) to introduce telomerase into endothelial cells, the prime target of chronic injury in allograft nephropathy (Young ATL, etal. In-Vitro Senescence Occurring in Normal Human Endothelial Cells can be rescued by Ectopic Telomerase Activity. Transplantation Proc 35(7):2483-5, November 2003). The overall aim is to genetically modify the allograft during ex-vivo perfusion prior to transplantation. We have also extended this strategy to islet cell transplants (Young AT, etal. Assessment of different transfection parameters in efficiency optimization. Cell Transplantation, In Press). This strategy would possibly allow the expansion of these single cell transplants and reduce the need for multiple donors for one successful islet transplant. Also in transplantation we are studying the co-transplantation of serotoli cells and islet cells. These serotoli or sustanticular cells prevent immunologic injury to the islet cells by way of FAS –FAS ligand interaction. This research is currently funded by the Kidney Foundation of Canada.
Featured Publications
Azad A, Campbell K, Zhabyeyev P, Oudit G, Moore RB
FASEB. 2022 October; 36 (10) 10.1096/fj.202200616RR
Liu R.Z., Choi W.S., Jain S., Dinakaran D., Xu X., Han W.H., Yang X.H., Glubrecht D.D., Moore R.B., Lemieux H., Godbout R.
Molecular Oncology. 2021 October; 14 (12):3100-3120 10.1002/1878-0261.12818
Inactivation of Endothelial Cell phosphoinositide 3-kinase (P13K) B Inhibits Renal Cell Carcinoma (RCC) Stimulated Angiogenesis and in vivo Tumor Growth
AUA Western Section. 2020 October;
Novel X-ray Activated Photodynamic (radioPDT) Nanoparticles for Deep Seated Tumors.
AUA Western Section. 2020 October;