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Introduction to Editorial Board Member: Professor David J. Mooney
Bioengineering & Translational Medicine ( IF 7.4 ) Pub Date : 2020-04-27 , DOI: 10.1002/btm2.10162
Ovijit Chaudhuri 1
Affiliation  

In this issue of Bioengineering and Translational Medicine , we are pleased to introduce our Editorial Board Member, Professor David J. Mooney (Figure 1). Professor Mooney is the Robert P. Pinkas Family Professor of Bioengineering at the John A. Paulson School of Engineering and Applied Sciences at Harvard University. He is a founding member of the Wyss Institute for Biologically Inspired Engineering at Harvard University, in which he serves as a core faculty member. He is a member of both the National Academy of Engineering and the National Academy of Medicine, and he is a fellow of the National Academy of Inventors. Professor Mooney is widely recognized for his influential work in biomaterials, drug delivery, tissue engineering and regenerative medicine, mechanotransduction, and immunotherapy. His publications have been cited over 90,000 times and include 13 papers with over 1,000 citations, his h‐index is 150, and he has given over 400 invited lectures. In 2019, Nature Biotechnology named him one of the top 10 translational researchers in biotechnology.

Professor Mooney earned his BS in Chemical Engineering at the University of Wisconsin, Madison. He then went on to conduct his PhD work in Chemical Engineering at the Massachusetts Institute of Technology, under the mentorship of Professor Robert Langer. After finishing his PhD, he worked as a postdoctoral fellow at Harvard University under the guidance of Dr Joseph Vacanti and Professor Donald Ingber. He started his career as a professor at the University of Michigan in 1994 and then moved to Harvard University in 2004.

In his early work, Professor Mooney made major advances in the use of biomaterials for regenerative medicine and tissue engineering. At the time, the paradigm in regenerative medicine had been the bolus delivery of single growth factors, which had limited efficacy. To address these limitations, Professor Mooney and others developed approaches to use biomaterial carriers for localized and sustained delivery of growth factors and other bioactive agents. His group demonstrated that modified, porous poly(lactide‐co‐glycolide) (PLG) scaffolds could deliver multiple growth factors with distinct kinetics to drive angiogenesis1 and bone formation, as well as deliver DNA‐encoding growth factors intracellularly to promote angiogenesis in vivo.2 They also developed a number of in vitro applications using these materials, including tissue‐engineered bone and models of tumors.3

Professor Mooney's early efforts also pioneered the use of alginate hydrogels for various biomedical applications.4 Alginate is a polysaccharide derived from algae, which forms a three‐dimensional (3D) nanoporous hydrogel when crosslinked with calcium that has similar structural characteristics to extracellular matrix. Alginate hydrogels are biocompatible, gel under mild conditions, and are injectable. Professor Mooney recognized and exploited these useful properties both in vivo and in vitro. His group showed how tuning various parameters, such as degradation and crosslinking, or applying mechanical perturbation can be used to control the spatiotemporal release of single or multiple bioactive molecules.5, 6 They utilized alginate gels to deliver a wide variety of bioactive molecules, including vascular endothelial growth factor and other heparin‐binding growth factors that naturally bind to alginate, as well as other bioactive molecules that must first be packaged or tethered to control their release. These approaches were used to promote angiogenesis, bone formation, and smooth muscle tissue formation in vivo. In parallel, they demonstrated that coupling the RGD (Arginine‐Glycine‐Aspartate) cell adhesion peptide sequence to the alginate allows cells to adhere to the otherwise inert gels.7 This enabled in vivo regenerative medicine applications involving infiltration of host cells into gels or delivery of exogenous cells, as well as two‐dimensional (2D) and 3D culture of adherent cells in vitro.

Professor Mooney's group continues to work on applying alginate toward therapeutic angiogenesis and regeneration of musculoskeletal tissues. Furthermore, they have continued to innovate with alginate, introducing various ways to modify the gels chemically and physically and expanding their use to new applications. Recent developments include alginate‐based tough gels8 and tough adhesives.9

Professor Mooney is also a leader in the field of mechanotransduction, the process by which cells sense and respond to mechanical cues. Professor Mooney's group has extensively characterized the mechanical properties of alginate gels and elucidated their underlying mechanisms; based on this knowledge, they have devised various approaches to modulate the mechanical properties of alginate‐based materials. In their early studies, they discovered that the stiffness of RGD‐coupled alginate hydrogels impacts cell proliferation, apoptosis, and differentiation in 2D culture, and they identified integrin clustering as a key mediator of mechanotransduction.10 They went on to show that hydrogel stiffness regulates the differentiation of mesenchymal stem cells in 3D culture11 and applied this finding to design a material that optimally promotes bone regeneration in vivo. Professor Mooney also recognized that tissues and extracellular matrices are typically not elastic but viscoelastic. His group developed alginate hydrogels with tunable viscoelasticity and showed that viscoelasticity, independent of stiffness, had a striking impact on various cell behaviors, including proliferation and stem cell differentiation, in both 2D culture and 3D culture.12 The role of matrix viscoelasticity in mechanotransduction has recently emerged as a major area of study in the field.

Professor Mooney is also a pioneer in the emerging field of immunoengineering, with a particular focus on cancer immunotherapy. In a seminal study, his group demonstrated that biomaterials could be used to develop potent cancer vaccines. PLG scaffolds delivering tumor‐specific antigens and danger signals were implanted in vivo to elicit a cytotoxic immune response against melanoma cells, representing the first therapeutic vaccine to eliminate melanoma tumors in mice.13 This technology recently completed a Phase I clinical trial in Stage IV melanoma patients. They have extended this approach to other types of cancer, as well as other biomaterial platforms, including alginate and a novel injectable mesoporous silica rod‐based system.14 The cancer vaccine technology is currently being commercialized by Novartis. Professor Mooney's group is also applying biomaterials to other areas in immunoengineering, such as promoting antigen‐specific tolerogenic responses, enhancing T‐cell regeneration after hematopoietic stem cell transplantation, and expanding T‐cells ex vivo.15

Beyond his scientific contributions, Professor Mooney has had a major impact at Harvard and in the broader bioengineering community through his service. He plays an active role in the National Academies and currently chairs Section 2 (Bioengineering) at the National Academy of Engineering. He serves as an editorial advisor to several journals and publishers, participates on several industry advisory boards, and serves on the visiting committees for a number of universities.

Last but not least, Professor Mooney is also a fantastic research mentor and role model to his trainees. He has trained 55 PhD students, 61 postdoctoral fellows, 25 M.S. students, and over 100 undergraduates in his laboratory (Figure 2). Despite having a large research group, he is deeply committed to mentoring each of his trainees and gives each of his trainees the support they need to pursue their individual research interests. Following his lead, members of the Mooney lab form a strong and supportive community, and many of us who go onto academic positions strive to emulate his mentorship style. Long after we leave his group, we continue to benefit from his advice and mentorship, as well as from the connection to the extensive network of Mooney alumni. Professor Mooney's excellent mentorship has been recognized by two major awards at Harvard: the Capers and Marion McDonald Award for Excellence in Mentoring and Advising at the School of Engineering and Applied Sciences and the Everett Mendelsohn Excellence in Mentoring Award bestowed by the Graduate Student Council. On behalf of his current and former trainees, I express my deep gratitude to Dave for the scientific opportunities we had with him and his mentorship and guidance.

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FIGURE 1
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Professor Mooney after receiving the Everett Mendelsohn Excellence in Mentoring Award, given by the Graduate Student Council at Harvard University, in 2013. Photo courtesy of Dr Luo Gu
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FIGURE 2
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The Mooney lab group photo in 2012. Photo courtesy of the Mooney group


中文翻译:

编辑委员会成员简介:David J. Mooney教授

在本期《生物工程与转化医学》中,我们很高兴向您介绍我们的编辑委员会成员David J. Mooney教授(图1)。Mooney教授是哈佛大学John A. Paulson工程与应用科学学院的Robert P. Pinkas家庭生物工程教授。他是哈佛大学Wyss生物启发工程研究所的创始成员,也是该中心的核心成员。他是美国国家工程研究院和美国国家医学研究院的成员,也是美国国家发明家研究院的成员。Mooney教授因其在生物材料,药物输送,组织工程和再生医学,机械转导和免疫疗法方面的影响力而广受认可。他的出版物已被引用超过90,000次,其中包括13篇论文,被引用超过1000篇,他的h指数是150,他已举办了400多场讲座。在2019年《自然生物技术》将他评为生物技术领域十大转化研究人员之一。

Mooney教授在麦迪逊的威斯康星大学获得了化学工程学士学位。然后,他在罗伯特·兰格(Robert Langer)教授的指导下,继续在麻省理工学院进行化学工程博士学位。完成博士学位后,他在约瑟夫·瓦卡蒂博士和唐纳德·英格伯教授的指导下在哈佛大学担任博士后。他的职业生涯始于1994年,当时是密歇根大学的教授,然后于2004年移居哈佛大学。

在其早期工作中,穆尼教授在将生物材料用于再生医学和组织工程学方面取得了重大进展。当时,再生医学的范例是推注单一生长因子,但疗效有限。为了解决这些限制,Mooney教授和其他人开发了使用生物材料载体来局部和持续递送生长因子和其他生物活性剂的方法。他的研究小组证明,修饰的多孔聚(丙交酯-共-乙交酯)(PLG)支架可以传递具有多种动力学特性的多种生长因子,以驱动血管生成1和骨形成,还可以在细胞内传递编码DNA的生长因子,从而促进体内血管生成。 。2他们还使用这些材料开发了许多体外应用,包括组织工程骨和肿瘤模型。3

Mooney教授的早期努力还开创了藻酸盐水凝胶在各种生物医学应用中的应用。4海藻酸盐是衍生自藻类的多糖,当与钙交联时会形成三维(3D)纳米多孔水凝胶,钙的结构特征与细胞外基质相似。藻酸盐水凝胶具有生物相容性,可在温和条件下凝胶化,并且可注射。Mooney教授认识到并利用了这些有用的体内和体外特性。他的小组展示了如何调整各种参数,例如降解和交联,或应用机械扰动来控制单个或多个生物活性分子的时空释放。5、6他们利用藻酸盐凝胶传递多种生物活性分子,包括天然与藻酸盐结合的血管内皮生长因子和其他肝素结合生长因子,以及必须首先包装或栓系以控制其释放的其他生物活性分子。这些方法用于促进体内血管生成,骨形成和平滑肌组织形成。同时,他们证明了将RGD(精氨酸-甘氨酸-天门冬氨酸)细胞粘附肽序列与藻酸盐偶联可以使细胞粘附到其他惰性凝胶上。7这使得体内再生医学应用得以实现,其中涉及宿主细胞渗入凝胶或外源细胞的递送,以及体外贴壁细胞的二维(2D)和3D培养。

Mooney教授的小组继续致力于将藻酸盐应用于治疗性血管生成和肌肉骨骼组织的再生。此外,他们继续利用藻酸盐进行创新,引入了各种方法来化学和物理修饰凝胶,并将其用途扩展到新的应用领域。最近的发展包括基于藻酸盐的硬质凝胶8和硬质粘合剂。9

Mooney教授还是机械转导领域的领导者,机械转导是细胞感知并响应机械提示的过程。Mooney教授的研究小组对海藻酸盐凝胶的机械性能进行了广泛表征,并阐明了其潜在机理。基于这些知识,他们设计了各种方法来调节藻酸盐基材料的机械性能。在他们的早期研究中,他们发现RGD耦合藻酸盐水凝胶的刚度会影响2D培养中的细胞增殖,凋亡和分化,并且他们发现整联蛋白簇是机械转导的关键介质。10他们继续证明水凝胶刚度调节3D培养中的间充质干细胞的分化11并运用这一发现设计出了一种能够在体内最佳促进骨骼再生的材料。Mooney教授还认识到组织和细胞外基质通常不是弹性的而是粘弹性的。他的小组开发了具有可调粘弹性的藻酸盐水凝胶,并表明粘弹性与硬度无关,对2D培养和3D培养中的各种细胞行为(包括增殖和干细胞分化)都具有显着影响。12基质粘弹性在机械转导中的作用最近成为该领域的主要研究领域。

Mooney教授还是免疫工程领域新兴的先驱,特别关注癌症免疫治疗。在一项开创性研究中,他的小组证明了生物材料可用于开发有效的癌症疫苗。PLG支架在体内植入了传递肿瘤特异性抗原和危险信号的支架,以引发针对黑素瘤细胞的细胞毒性免疫反应,这是消除小鼠黑素瘤肿瘤的首个治疗性疫苗。13该技术最近在IV期黑色素瘤患者中完成了I期临床试验。他们将这种方法扩展到了其他类型的癌症以及其他生物材料平台,包括藻酸盐和新型可注射的介孔二氧化硅棒为基础的系统。14诺华公司目前正在将癌症疫苗技术商业化。Mooney教授的小组还在免疫工程学的其他领域应用生物材料,例如促进抗原特异性的致耐受性反应,在造血干细胞移植后增强T细胞再生以及离体扩增T细胞。15

除了他的科学贡献外,穆尼教授还通过他的服务对哈佛大学以及更广泛的生物工程界产生了重大影响。他在美国国家科学院中扮演着积极的角色,目前在美国国家工程学院担任第二部分(生物工程)的主席。他是多家期刊和出版商的编辑顾问,还参加了多个行业顾问委员会,并在许多大学的访问委员会中担任过职务。

最后但并非最不重要的一点是,穆尼教授还是受训人员的出色研究导师和榜样。他在实验室培训了55名博士生,61名博士后研究员,25名MS学生和100多名本科生(图2)。尽管拥有庞大的研究团队,他仍然致力于指导每个受训者,并为每个受训者提供追求他们个人研究兴趣所需的支持。在他的领导下,门尼实验室的成员组成了一个强大而相互支持的社区,我们中许多担任学术职务的人都在努力效法他的指导风格。在离开他的团队很久以后,我们继续从他的建议和指导以及与门尼校友广泛网络的联系中受益。穆尼教授 哈佛大学的两项杰出奖项被授予了杰出的指导奖:工程与应用科学学院的Capers和Marion McDonald优秀指导和咨询奖以及研究生理事会授予的Everett Mendelsohn优秀指导奖。我代表他的现任和前任学员,对戴夫与他一起获得的科学机会以及他的指导和指导深表感谢。

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Mooney教授在2013年获得哈佛大学研究生理事会颁发的Everett Mendelsohn优秀指导奖之后。照片由罗Lu博士提供
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图2
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Mooney实验室在2012年的集体合影。照片由Mooney团体提供
更新日期:2020-04-27
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