米歇尔-蒙杰 神经科学家和神经肿瘤学家

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Michelle Monje
Neuroscientist and Neuro-Oncologist | Class of 2021
Advancing understanding of pediatric brain cancers and the neurological effects of cancer treatments with an eye toward improved therapies for patients.


Portrait of Michelle Monje

Title
Neuroscientist and Neuro-Oncologist
Affiliation
Department of Neurology and Neurological Sciences, Stanford University
Location
Palo Alto, California
Age
45 at time of award
Area of Focus
Neuroscience and Neurobiology, Public Health and Biomedical/Health Sciences
Website
Monje Lab
Stanford University: Michelle Monje
Social
Twitter
Published September 28, 2021
ABOUT MICHELLE'S WORK
Michelle Monje is a neuroscientist and neuro-oncologist advancing our understanding of postnatal brain development and translating her findings into promising therapies for pediatric brain tumors. As both a practicing physician and research scientist, Monje brings a unique perspective to her study of the interplay of neuron and glial (support) cells in healthy and diseased states. The potential for her research to translate to clinical treatments for pediatric cancer patients guides many of her projects.

In early work, Monje and her students provided evidence that neuronal activity drives key aspects of brain development. In particular, they found it induces the proliferation of oligodendrocyte precursor cells (a type of glial cell) and increases myelination (the process of protecting and enhancing connections between neurons with an insulating sheathing). Based on this evidence in healthy brain development, Monje hypothesized that neuronal activity may also be driving brain tumor, or glioma, growth, specifically the growth of a lethal childhood brain cancer called diffuse intrinsic pontine glioma (DIPG). She recently made the groundbreaking discovery that glioma cells (including DIPG cells) form electrophysiologically functional synapses with neurons and that these connections produce a positive feedback mechanism that drives tumor development. Monje and colleagues also demonstrated that growth factors released during brain activity, particularly the synaptic protein neuroligin-3, promote the growth of high-grade (fast-growing) gliomas. Monje plays an active role in bringing her findings into clinical settings. She showed that blocking neuroligin-3 secretion in the tumor microenvironment dramatically slows the growth of fast-growing and aggressive tumors (including glioblastoma and DIPG) in mice. In collaboration with other labs, she identified a molecule on the surface of gliomas to target with CAR T-cell therapy (a type of immunotherapy), resulting in the virtual elimination of the tumors in mice. She is currently leading clinical trials for these and other treatment methods.

Monje’s research includes the negative effects chemotherapy has on the developing brain, such as learning and social disabilities that can develop and persist for months or years. Often referred to as “chemobrain,” symptoms include memory lapses, slowed thinking, and mental fog. In a recent study, Monje and colleagues showed that chemotherapy depletes the oligodendrocyte cells required to make myelin and over-activates the microglia (immune cells). Her lab demonstrated that selective depletion of the microglia reversed many of the cognitive symptoms of “chemobrain.” A compassionate physician committed to patient outcomes and a high-impact researcher, Monje is opening new pathways for the study of cancer pathogenesis with the potential to transform treatment of brain cancers.

BIOGRAPHY
Michelle Monje received a BA (1998) from Vassar College and an MD and PhD (2004) from Stanford University. She completed her residency at Harvard Medical School in the Brigham and Women’s Hospital and Massachusetts General Hospital before returning to Stanford for clinical and postdoctoral fellowships. In 2011, Monje joined the faculty at Stanford, where she now serves as an associate professor in the Department of Neurology and Neurological Sciences. In 2021, she was selected as a Howard Hughes Medical Institute Investigator. Her papers have been published in Nature, Science, Cell, Neuron, and Molecular Cell, among other scientific journals.

IN MICHELLE'S WORDS
Smiling white woman with blonde hair wearing a white lab coat stands in room with medical equipment. Quote text below photo reads: My greatest source of both inspiration and motivation are my patients. Seeing children fight lethal brain cancers with grace really frames the work that needs to be done.


My greatest source of both inspiration and motivation are my patients. Their diseases demand that we challenge our assumptions, and their courage and strength compel me to work harder. When I first encountered brain cancers like diffuse intrinsic pontine glioma and glioblastoma, it struck me that most of what I had been taught about cancer seemed not to apply to these diseases, and so it was not surprising that typical cancer therapies did not work very well. When a problem seems insoluble, it often helps to take a big step back and look at it from a different angle. I thought it might be helpful to look at these cancers of the nervous system from the perspective of neuroscience. It has been at the intersection of different fields—neuroscience and cancer biology, neuroscience and immunology, immunology and cancer biology, basic science and clinical medicine—that the key insights have emerged in my work. Diversity of perspective is crucial for progress and discovery, and I seek diversity of perspective both in myself and in my research team. Seeing children fight lethal brain cancers with grace really frames the work that needs to be done.



米歇尔-蒙杰
神经科学家和神经肿瘤学家｜2021级
推进对小儿脑癌和癌症治疗对神经系统影响的了解，以改善患者的治疗。


米歇尔-蒙杰的肖像

标题
神经科学家和神经肿瘤学家
工作单位
斯坦福大学神经病学和神经科学系
工作地点
加州帕洛阿尔托
年龄
获奖时45岁
重点领域
神经科学和神经生物学, 公共卫生和生物医学/健康科学
网站
蒙杰实验室
斯坦福大学。米歇尔-蒙杰
社会
推特
2021年9月28日发布
关于Michelle的工作
米歇尔-蒙杰是一位神经科学家和神经肿瘤学家，她推动了我们对产后大脑发育的理解，并将她的发现转化为对小儿脑瘤的有希望的治疗方法。作为一名执业医师和研究科学家，蒙杰以独特的视角研究了神经元和胶质（支持）细胞在健康和疾病状态下的相互作用。她的研究有可能转化为对儿科癌症患者的临床治疗，这指导了她的许多项目。

在早期的工作中，蒙杰和她的学生提供了神经元活动驱动大脑发育的关键方面的证据。特别是，他们发现它能诱导少突胶质细胞前体细胞（一种胶质细胞）的增殖，并增加髓鞘化（用绝缘鞘保护和加强神经元之间连接的过程）。基于健康大脑发育的这一证据，Monje假设神经元活动也可能推动脑肿瘤或胶质瘤的生长，特别是一种被称为弥漫性桥脑胶质瘤（DIPG）的致命的儿童脑癌的生长。她最近取得了突破性的发现，胶质瘤细胞（包括DIPG细胞）与神经元形成了具有电生理功能的突触，这些连接产生了一种正反馈机制，驱动肿瘤的发展。Monje及其同事还证明，大脑活动期间释放的生长因子，特别是突触蛋白neuroligin-3，促进了高等级（快速生长）胶质瘤的生长。Monje在将她的发现引入临床方面发挥了积极作用。她表明，阻断肿瘤微环境中的neuroligin-3的分泌，可以极大地减缓小鼠体内快速生长和侵略性肿瘤（包括胶质母细胞瘤和DIPG）的生长。她与其他实验室合作，确定了胶质瘤表面的一种分子，以CAR T细胞疗法（一种免疫疗法）为目标，使小鼠体内的肿瘤几乎被消除了。她目前正在领导这些和其他治疗方法的临床试验。

蒙杰的研究包括化疗对发育中的大脑产生的负面影响，如学习和社交障碍，这些障碍可以发展并持续数月或数年。通常被称为 "化学脑"，其症状包括记忆缺失、思维迟钝和精神雾霾。在最近的一项研究中，Monje及其同事表明，化疗消耗了制造髓鞘所需的少突胶质细胞，并过度激活了小胶质细胞（免疫细胞）。她的实验室证明，选择性地耗尽小胶质细胞可以逆转 "化脑 "的许多认知症状。作为一个致力于病人治疗的富有同情心的医生和一个有影响力的研究者，蒙杰正在为癌症发病机制的研究开辟新的途径，有可能改变脑癌的治疗。

个人简历
米歇尔-蒙杰在瓦萨学院获得学士学位（1998年），在斯坦福大学获得医学博士和博士学位（2004年）。她在哈佛医学院布里格姆妇女医院和马萨诸塞州总医院完成了住院医师培训，然后回到斯坦福大学从事临床和博士后研究工作。2011年，蒙杰加入了斯坦福大学的教师队伍，现在她担任神经病学和神经科学系的副教授。2021年，她被选为霍华德-休斯医学研究所调查员。她的论文发表在《自然》、《科学》、《细胞》、《神经元》、《分子细胞》等科学期刊上。

用米歇尔的话说
身穿白大褂的金发白人妇女微笑着站在有医疗设备的房间里。照片下面的引言文字是：。我最大的灵感和动力来源是我的病人。看到孩子们优雅地与致命的脑癌作斗争，这确实是需要做的工作的框架。


我最大的灵感和动力来源是我的病人。他们的疾病要求我们挑战我们的假设，而他们的勇气和力量迫使我更加努力工作。当我第一次遇到像弥漫性桥脑胶质瘤和胶质母细胞瘤这样的脑癌时，我突然发现，我所学到的关于癌症的大部分知识似乎并不适用于这些疾病，因此，典型的癌症疗法效果不佳也就不足为奇。当一个问题似乎无法解决时，退后一大步，从不同的角度来看待它，往往会有帮助。我想，从神经科学的角度来看待这些神经系统的癌症可能会有帮助。正是在不同领域--神经科学和癌症生物学、神经科学和免疫学、免疫学和癌症生物学、基础科学和临床医学--的交叉点上，我的工作中出现了关键的见解。观点的多样性对进步和发现至关重要，而我在自己和我的研究团队中都寻求观点的多样性。看到孩子们优雅地与致命的脑癌作斗争，确实为需要完成的工作提供了框架。