几十年来，约翰 · 莫德博士一直是一位领先的放射生物学家之一，并且是极少数不断支持研究放射治疗对正常组织影响的人之一。他精细的建模和跨领域的合作提供了一个充分的例子，说明研究可以从实验室带到床头，再从床头带回实验室，最终目的是为患者提供利益。约翰的许多工作重点是减轻肾损伤，无论是意外还是故意的临床暴露结果。在他的脚步中，我们在这里提供了一份辐射诱导的膀胱损伤领域研究的简要概述。然后，我们描述了我们自己的临床基因组关联研究(GWAS)的响应而开展的临床前实验研究，探究放射治疗前列腺癌患者的基因组生物标志物的正常组织毒性。我们特别讨论了肾素 - 血管紧张素系统(RAS)抑制剂作为损伤调节剂的应用，这是莫德勒小组倡导的一种药物，以及RAS抑制剂与某些毒性指标降低相关的情况。使用小鼠模型以及精确的 CT 影像引导下的膀胱单剂量和分剂量放疗方案，我们能够证明放射引起的膀胱功能损伤，以及通过靶向 RAS 的血管紧张素转化酶抑制剂减轻这种功能性损伤，这种实验方法类似于莫德勒小组使用的实验方法。我们认为我们的科学轨迹是从床边到实验室的方法，因为观察是临床进行的，然后在临床前模型中进行了调查；这种实验方法符合约翰 · 莫德博士良好的职业生涯。尽管功能终点存在差异，最近的研究结果表明，膀胱晚期反应和约翰 · 莫德博士开创的肾工作存在共性。我们提供证据，证明靶向 RAS 途径可以提供一个可靶向的途径，减少晚期膀胱毒性。

For decades, Dr. John Moulder has been a leading radiation biologist and one of the few who consistently supported the study of normal tissue responses to radiation. His meticulous modeling and collaborations across the field have offered a prime example of how research can be taken from the bench to the bedside and back, with the ultimate goal of providing benefit to patients. Much of the focus of John's work was on mitigating damage to the kidney, whether as the result of accidental or deliberate clinical exposures. Following in his footsteps, we offer here a brief overview of work conducted in the field of radiation-induced bladder injury. We then describe our own preclinical experimental studies which originated as a response to reports from a clinical genome-wide association study (GWAS) investigating genomic biomarkers of normal tissue toxicity in prostate cancer patients treated with radiotherapy. In particular, we discuss the use of Renin-Angiotensin System (RAS) inhibitors as modulators of injury, agents championed by the Moulder group, and how RAS inhibitors are associated with a reduction in some measures of toxicity. Using a murine model, along with precise CT-image guided irradiation of the bladder using single and fractionated dosing regimens, we have been able to demonstrate radiation-induced functional injury to the bladder and mitigation of this functional damage by an inhibitor of angiotensin converting enzyme targeting the RAS, an experimental approach akin to that used by the Moulder group. We consider our scientific trajectory as a bedside to bench approach because the observation was made clinically and investigated in a preclinical model; this experimental approach aligns with the exemplary career of Dr. John Moulder.Despite the differences in functional endpoints, recent findings indicate a commonality between bladder late effects and the work in kidney pioneered by Dr. John Moulder. We offer evidence that targeting the RAS pathway may provide a targetable pathway to reducing late bladder toxicity.