Meet up-and-coming analytical scientists – Fabio Pereira Gomes

IF 3 Q2 CHEMISTRY, ANALYTICAL
Fabio Pereira Gomes
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I then moved to the University of Queensland (Australia) to complete my PhD in Analytical Chemistry. After graduation, I moved to the United States where I have held postdoctoral positions in two laboratories led by world leader proteomics: first with Dr. Catherine Fenselau at the University of Maryland (2017–2018) and currently with Dr. John R. Yates III at the Scripps Research (2018–present).</p><p>I have 2 overaching research goals. My first goal is to develop and improve technologies for probing intact proteoforms and their complexoforms within the intracellular space. My second goal is to apply these technologies to better understand the molecular mechanisms that govern metastatic tumors, drug resistance, and how lipids bind and modulate the biological activities of important drug targets such as membrane proteins. I am excited about the native top-down proteomics (nTDP) strategy I developed to interrogate complexoforms in breast cancer cells. 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For example, proteoforms and their complexoforms in biologically relevant samples can be separated by chromatography or electrophoresis, and then powerful analytical techniques such as MS can be used to precisely identify and quantify these macromolecules and other biomolecules in the eluates.</p><p>As mentioned previously, I am currently developing TDP-based methods to test the hypothesis that the biological actions of estrogens and antiestrogen drugs in the development of breast cancer and resistance to endocrine therapy are regulated by ER-alpha proteoforms and complexoforms. I want to define how different receptor proteoforms and complexoforms lead to specific signaling outcomes and how these are impacted by endocrine treatments and growth factor-mediated resistance. 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引用次数: 0

Abstract

Analytical sciences are among the most dynamically developing fields and have been inherently integrated into many various scientific disciplines. At the same time, early career researchers (ECRs) are among those whose contribution to this dynamic growth cannot be simply overestimated. Hence, in this special issue “From one ECR to the next”, we are presenting a series of editorials with questions and answers from five emerging scientists from different analytical fields including omics, environmental and data sciences. Importantly, all our guests boast not only scientific excellence and high-quality research but also the substantial international experience gained during their PhD or postdoctoral training. For this editorial, we are presenting Dr. Fabio P. Gomes.

Dr. Gomes is a Postdoctoral Researcher at the Scripps Research. He holds a Ph.D. in Analytical Chemistry from the University of Queensland. His research interests include the use of innovative mass spectrometry (MS)-based methods to investigate the structure-function relationship of intact proteoforms and their complexoforms withincells. He is currently developing and applying MS approaches to structurally elucidate intact complexoforms (protein complexes formed by intact monomeric proteoform arrangements) in breast cancer cells, and to interrogate intact proteoforms in single cardiomyocyte cells. Proteins adopt multiple proteoforms as a result of various structural changes (e.g. posttranslational modifications [PTMs] and truncations).

I am an Afro-Brazilian citizen and US permanent resident. I was born and raised in Sao Paulo (Brazil), where I completed both my undergraduate degree and a master's degree with graduate research in Pharmaceutical Sciences. I then moved to the University of Queensland (Australia) to complete my PhD in Analytical Chemistry. After graduation, I moved to the United States where I have held postdoctoral positions in two laboratories led by world leader proteomics: first with Dr. Catherine Fenselau at the University of Maryland (2017–2018) and currently with Dr. John R. Yates III at the Scripps Research (2018–present).

I have 2 overaching research goals. My first goal is to develop and improve technologies for probing intact proteoforms and their complexoforms within the intracellular space. My second goal is to apply these technologies to better understand the molecular mechanisms that govern metastatic tumors, drug resistance, and how lipids bind and modulate the biological activities of important drug targets such as membrane proteins. I am excited about the native top-down proteomics (nTDP) strategy I developed to interrogate complexoforms in breast cancer cells. I plan to extend this approach to investigate the hypothesis that the biological actions of estrogen and antiestrogen drugs in the development of metastatic breast tumors and drug resistance are regulated by estrogen receptor alpha (ER-alpha) proteoforms and complexoforms. I am also enthusiastic about the top-down proteomics (TDP) strategy I developed to interrogate intact proteoforms in single cardiomyocyte cells. I plan to extend this approach to capture the breast cancer cell-to-cell heterogeinety. I will soon be submitting two first-author manuscripts for publication that are related to these two efforts.

Discovery is my major motivation. Analytical Science is a fascinating branch of chemistry that allows scientists to gain insights into the structure and properties of biological systems by better understanding complex biological processes at the molecular level. This information can then be used to develop effective therapeutic interventions. For example, proteoforms and their complexoforms in biologically relevant samples can be separated by chromatography or electrophoresis, and then powerful analytical techniques such as MS can be used to precisely identify and quantify these macromolecules and other biomolecules in the eluates.

As mentioned previously, I am currently developing TDP-based methods to test the hypothesis that the biological actions of estrogens and antiestrogen drugs in the development of breast cancer and resistance to endocrine therapy are regulated by ER-alpha proteoforms and complexoforms. I want to define how different receptor proteoforms and complexoforms lead to specific signaling outcomes and how these are impacted by endocrine treatments and growth factor-mediated resistance. I am particularly excited about this work because I strongly believe it will have a very high impact on many fields, including estrogen receptor biology, basic mechanisms of transcription and the study of proteoforms more generally, which will significantly impact the understanding of resistance to endocrine therapy as well as cancer signalling and heterogeneity.

Over the course of my PhD, I became very interested in protein MS. Most cellular functions, including those linked to pathological and physiological states, are performed by protein complexes that often assemble via non-covalent interactions of monomeric protein subunits. As mentioned previously, proteins adopt multiple proteoforms as a result of various structural changes (e.g. PTMs and truncations). Proteoforms influence the formation, stability and activity of functional protein complexes, and can form numerous functional “complexoforms” from a single protein complex. Individual proteoforms can independently modulate numerous biological processes, and they may also serve as important markers of disease. MS allows scientists to understand the molecular basis of physiological and pathological processes and to identify novel drug targets that can ultimately help patients. Thus, for my postdoctoral training, I decided to pursue research that uses MS-based methods and biological techniques to elucidate the structure of proteoforms and their complexoforms in the intracellular space.

Brazil is largely influenced by American culture. For instance, several people in Brazil celebrate Thanksgiving and have Halloween parties. In addition, American music and movies are predominant in many parts of Brazil, so I was aware of many things about American culture before moving to the United States. While I continue to admire American culture, I was surprised by the underrepresentation of black scientists in academic and industrial settings. I now understand that this is a global issue; I have observed racial disparities in all the countries I lived in, including Brazil, Australia and Germany. Sadly, there are still many institutional, social and emotional barriers that impede talented black children from becoming scientists.

As a graduate student and postdoctoral researcher, I have been fortunate to benefit from supportive mentors and colleagues who provided/provide me with useful advice for building a career as a successful independent scientist. Among the many important pieces of advice, I would say that “Be courageous, innovative, collaborative and respectful, as well as learn from your mistakes as they are necessary to make you a better colleague/scientist and to get the right answers” might be the best.

Make sure you know what you want for your future career and then choose a lab that can help you to achieve your career goal. On top of your strong desire and motivation to succeed, a supportive postdoctoral adviser and a productive and collaborative environment can be key to your career growth. Learn as much as possible from colleagues, mentors and collaborators. Publish quality papers and make sure the quality of the paper is the same for high-impact or low-impact factor journals. Write papers, reviews and grants, even if you will not pursue an academic career. I believe that the ability to communicate effectively (speaking and writing) will open doors and make a significant difference in your career in either industry or academic settings. Work with your heart, be kind and friendly and listen to advise but make your decisions.

I enjoy many different things, such as listening to music, watching movies, swimming, going out with my wife, spending time with my friends, playing soccer and having a good beer. I also enjoy calling my mother and niece in Brazil. Getting together for barbecues is also fun. My wife and I make barbecues all the time.

There are many people I would like to invite to my dream dinner party, including my mother, niece and wife, but I would also love to invite Serena Williams, Barack Obama and Michael Jordan. As an international tennis legend, Serena Williams has been a role model for black children worldwide, especially girls from underprivileged communities. Barack Obama's landmark election as the first Afro-American president of the United States was a transformative event for black people across the globe, giving them hope that everything is possible with hard work and education. I would include Michael Jordan because of the profound effect his magic moves had on me as a young fan and on the sport of basketball. Michael Jordan is still a source of inspiration for many people and will be remembered as the greatest or one of the greatest basketball players ever. His post-basketball career success would make him an even more interesting dinner guest.

The author declares no conflict of interest.

遇见未来的分析科学家- Fabio Pereira Gomes
分析科学是最具活力的发展领域之一,并已内在地融入许多不同的科学学科。与此同时,早期职业研究人员(ecr)是对这种动态增长的贡献不能简单高估的人之一。因此,在本期“从一个ECR到下一个ECR”特刊中,我们将展示来自不同分析领域(包括组学,环境和数据科学)的五位新兴科学家的一系列问题和答案。重要的是,我们所有的客人不仅拥有卓越的科学成就和高质量的研究,而且在博士或博士后培训期间获得了丰富的国际经验。在这篇社论中,我们请到了Fabio P. gomes博士。戈麦斯是斯克里普斯研究所的博士后研究员。他拥有昆士兰大学分析化学博士学位。他的研究兴趣包括使用创新的基于质谱(MS)的方法来研究细胞内完整的蛋白质形态及其复杂形态的结构-功能关系。他目前正在开发和应用质谱方法,从结构上阐明乳腺癌细胞中完整的复杂形态(由完整的单体蛋白质形态排列形成的蛋白质复合物),并询问单个心肌细胞中完整的蛋白质形态。由于各种结构变化(如翻译后修饰[PTMs]和截断),蛋白质采用多种蛋白质形态。我是一名非裔巴西公民和美国永久居民。我在巴西圣保罗出生和长大,在那里我完成了我的本科学位和硕士学位,并进行了研究生的药学研究。然后我搬到昆士兰大学(澳大利亚)完成我的分析化学博士学位。毕业后,我搬到美国,在世界蛋白质组学领导者领导的两个实验室担任博士后职位:首先是马里兰大学的Catherine Fenselau博士(2017-2018),目前是Scripps Research的John R. Yates III博士(2018 -至今)。我有两个宏大的研究目标。我的第一个目标是开发和改进在细胞内空间探测完整的蛋白质形态及其复杂形态的技术。我的第二个目标是应用这些技术来更好地理解控制转移性肿瘤、耐药性的分子机制,以及脂质如何结合和调节重要药物靶点(如膜蛋白)的生物活性。我对我开发的天然自顶向下蛋白质组学(nTDP)策略感到兴奋,该策略用于询问乳腺癌细胞中的复杂形态。我计划扩展这一方法,研究雌激素和抗雌激素药物在转移性乳腺肿瘤发生和耐药过程中的生物学作用是由雌激素受体α (er - α)蛋白形态和复合形态调节的这一假设。我对自上而下的蛋白质组学(TDP)策略也很感兴趣,我开发了这种策略来询问单个心肌细胞中完整的蛋白质形态。我计划扩展这种方法来捕捉乳腺癌细胞间的异质性。我将很快提交两份第一作者的手稿发表,这两份手稿与这两项努力有关。探索是我的主要动力。分析科学是化学的一个引人入胜的分支,它使科学家能够通过在分子水平上更好地理解复杂的生物过程来洞察生物系统的结构和特性。这些信息可用于制定有效的治疗干预措施。例如,生物相关样品中的蛋白质形态及其复杂形态可以通过色谱或电泳分离,然后可以使用质谱等强大的分析技术精确地识别和定量这些大分子和洗脱液中的其他生物分子。如前所述,我目前正在开发基于tdp的方法,以验证雌激素和抗雌激素药物在乳腺癌发展和内分泌治疗耐药中的生物学作用是由er - α蛋白形式和复杂形式调节的假设。我想定义不同的受体蛋白形态和复杂形态如何导致特定的信号结果,以及这些如何受到内分泌治疗和生长因子介导的抗性的影响。我对这项工作感到特别兴奋,因为我坚信它将对许多领域产生非常高的影响,包括雌激素受体生物学、转录的基本机制和更广泛的蛋白质形态研究,这将显著影响对内分泌治疗耐药性的理解,以及癌症信号传导和异质性。在攻读博士学位的过程中,我对蛋白质质谱产生了浓厚的兴趣。 大多数细胞功能,包括那些与病理和生理状态相关的功能,都是由蛋白质复合物执行的,这些蛋白质复合物通常通过单体蛋白质亚基的非共价相互作用而组装。如前所述,由于各种结构变化(如PTMs和截断),蛋白质采用多种蛋白质形态。蛋白质形态影响功能性蛋白质复合物的形成、稳定性和活性,并且可以由单个蛋白质复合物形成许多功能性“复杂形态”。单个的蛋白质形态可以独立地调节许多生物过程,它们也可以作为疾病的重要标志。MS使科学家能够了解生理和病理过程的分子基础,并确定最终可以帮助患者的新型药物靶点。因此,在我的博士后培训中,我决定进行研究,利用基于质谱的方法和生物学技术来阐明细胞内空间中蛋白质形态及其复杂形态的结构。巴西很大程度上受到美国文化的影响。例如,巴西的一些人庆祝感恩节和万圣节派对。此外,美国的音乐和电影在巴西的许多地方都占主导地位,所以在搬到美国之前,我对美国文化有很多了解。虽然我仍然钦佩美国文化,但我对黑人科学家在学术和工业领域的代表性不足感到惊讶。我现在明白这是一个全球性的问题;在我生活过的所有国家,包括巴西、澳大利亚和德国,我都观察到了种族差异。可悲的是,仍然有许多制度、社会和情感上的障碍阻碍着有才华的黑人孩子成为科学家。作为一名研究生和博士后研究员,我很幸运地受益于支持我的导师和同事,他们为我提供了有用的建议,帮助我成为一名成功的独立科学家。在许多重要的建议中,我想说“勇敢、创新、合作和尊重,以及从错误中吸取教训,因为它们是使你成为更好的同事/科学家并得到正确答案所必需的”可能是最好的。确保你知道你未来的职业想要什么,然后选择一个可以帮助你实现职业目标的实验室。除了你对成功的强烈渴望和动力之外,一个支持你的博士后导师和一个富有成效和协作的环境是你职业发展的关键。从同事、导师和合作者那里尽可能多地学习。发表高质量的论文,并确保高影响因子和低影响因子期刊的论文质量是相同的。写论文、评论和申请,即使你不会追求学术生涯。我相信有效的沟通能力(口语和写作)将为你打开一扇大门,并在你的职业生涯中产生重大影响,无论是在工业还是学术环境中。用心工作,善良友好,听取建议,但自己做决定。我喜欢很多不同的事情,比如听音乐,看电影,游泳,和我的妻子出去,和我的朋友们在一起,踢足球,喝杯好啤酒。我也喜欢给我在巴西的母亲和侄女打电话。聚在一起烧烤也很有趣。我妻子和我经常做烧烤。我想邀请很多人参加我的梦想晚宴,包括我的母亲、侄女和妻子,但我也想邀请塞雷娜·威廉姆斯、巴拉克·奥巴马和迈克尔·乔丹。作为一名国际网球传奇人物,塞雷娜·威廉姆斯一直是全世界黑人儿童的榜样,尤其是来自贫困社区的女孩。巴拉克·奥巴马(Barack Obama)当选为美国第一位非洲裔总统,这对全球黑人来说是一个具有里程碑意义的事件,给了他们希望:只要努力工作和接受教育,一切皆有可能。迈克尔·乔丹也在其中,因为他的神奇动作对我这个年轻的篮球迷和篮球运动产生了深远的影响。迈克尔·乔丹仍然是许多人灵感的源泉,他将作为有史以来最伟大或最伟大的篮球运动员之一被人们铭记。他在篮球生涯结束后的成功将使他成为一个更有趣的晚宴嘉宾。作者声明不存在利益冲突。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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