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Building a Bridge Between Medicine and Basic Science

By: Phyllis A. Dennery, MD

How do physicians differ from basic scientists in their approach to diseases? The former provide insights into disease processes and their manifestations whereas, the latter delve deeply into mechanisms and look for potential therapeutic approaches. If we capitalize on these differences, this could lead to an ideal partnership between those who witness disease at the bedside and those who can adeptly use ever-evolving tools to elucidate the mechanistic underpinnings of human pathology.

Why is this partnership not always successful? Communication is often challenging due to limited understanding of each participants perspective. In fact, the gap is widening between the language spoken by biomedical scientists and clinicians/physician-scientists. With exponential advances in molecular biology and genetics, it has become difficult to incorporate these novel understandings into everyday medical practice.  Philosophically, the two groups have different goals. Science for the sake of science is laudable and necessary to organically discover new insights. However, the pressures of finding a solution for diseases exist and are much more vivid for the physician-scientists who want solutions for their patients. Clinicians want to save lives and have immediate impact but are hampered by the fear of injury and/or bad outcomes. Scientists are encouraged to challenge paradigms and to develop new approaches which leads to a new found knowledge without the fear of such consequences. There needs to be a way to bridge the divide between the culture of basic scientists and that of physician-scientists.

Of course, the integration of newfound knowledge of basic science insights into clinical decision making is important to improve patient care. However, once a discovery is made, dissemination and adoption in clinical practice is another significant hurdle which requires community engagement and public health support. This path is riddled with pitfalls. Therefore, it is often difficult to see how certain basic concepts lead to therapeutic interventions and to clinical successes. This has been a big challenge for redox biology in that despite years of clear ascertainment that antioxidants are beneficial to prevent cytotoxicity in various model systems, the applications to large scale human trials have been extremely limited and discouraging. This is likely due to the fact that the human organism is much more complex than any other laboratory-based model and there are many more factors that come into play to alter outcomes, in particular, disparities in healthcare delivery and lack of cultural competence. Nevertheless, a partnership between physicians and scientists may overcome these hurdles by identifying ways to enhance a particular benefit without causing harm.

Recently, we have seen some encouraging success stories around treatment of disease using redox biology concepts. Hopefully, this is the beginning of a new era. The process from discovery to implementations is long and  tortuous.   A recent publication reviewed the literature and identified papers where a scientific discovery was made followed by its adaptation into healthcare. On the average, it took 17 years for this to happen (1). This means that we have to tolerate the uncertainty between basic discoveries and eventual adaptation into clinical practice for many years and not lose faith. This is not for the faint of heart and requires constant vigilance to continue to focus on the ultimate goal through partnership and collaboration.  

Many will argue that we have to conduct science for the sake of science, rather than focus on finding an immediate solution to a disease process. I would say that we have to adopt both approaches. Families, patients, their families and communities rely on us to help improve their health. Without a goal towards therapeutic discoveries, we will extinguish their hopes and erode their faith in us.

How can we then work together as physician-scientists and basic scientists? We can be patient with each other in terms of understanding each other’s language. Oftentimes the physician rolls her eyes when PhD colleagues try to describe a disease process, smugly dismissing the limited understanding. In return, the basic scientist is exasperated by the approaches taken by the physician-scientist to solve a problem, and chastise him for his lack of rigor or his choice of vague assays. Working together and encouraging each other will go farther. Trying to formalize relationships between the most basic and most clinical investigators would make for an synergistic opportunity to accelerate discovery and implementation.

In the past 28 years, it has been my distinct pleasure to be engaged with SfRBM, known previously as the Society for Free Radical Biology and Medicine and The Oxygen Society. I have enjoyed every iteration of this Society and have felt compelled to be an active participant despite feeling inadequate in my lack of formal training in chemistry, biochemistry, molecular biology and genetics. I feel, nonetheless, that we physician-scientists can bring value to the Society in many ways.

As I approach the Presidency of the SfRBM as its first MD leader, I will look forward to working with you and learning from you to speak a common language that enhances scientific discovery and ultimately promotes health.   

1.         Morris ZS, Wooding S, Grant J. The answer is 17 years, what is the question: understanding time lags in translational research. J R Soc Med. 2011;104(12):510-20.

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Categories: Free Radical Biology and Medicine, Redox Biology


Exploring Careers In Industry: Where do I want to work… and who already works there?

Part 2 of 4 on “Exploring Careers in Industry” by SfRBM Nominations/Leadership Development Chair Anne Diers, Ph.D. (Dr. Diers on LinkedIn: https://www.linkedin.com/in/annerdiers/)

Looking for a job in academia versus elsewhere can be a very different process. LinkedIn is much more important in the non-academic setting. Make sure your LinkedIn page is current, professional, and thoughtful. You can also use LinkedIn to find out more about companies you're interested in, connect to people, network for informational interviews and/or positions (a personal introduction to a hiring manager can be very helpful), and look for position announcements. 

Connect with SfRBM on LinkedIn at - https://www.linkedin.com/company/society-for-free-radical-biology-and-medicine/

 
 

Making the leap to industry can be very challenging. You need to target your search and be very active in it - your time will be better spent networking than just applying positions from the comforts of your home.

For the hiring manager, their biggest concern is that they’ll make the wrong decision on who to hire, ending up with someone who is not be able to accomplish the business objectives at hand. With that perspective, it becomes clear that the best way to get a job in industry is to allay those fears in the hiring manager. Or in other words, connect your skills to the needs listed in the job posting – be specific! That middle-author manuscript you’re on because you did a bit of confocal microscopy for the lab down the hall should become “demonstrated proficiency working in a collaborative team environment” on your resume. It also helps to have a personal introduction if possible. To do this, you’ll need to identify an opening, and then get in touch with someone who can help you get that introduction. Again, LinkedIn can help you get started; you can see who’s where and identify the connections you may not even know you already have. And don’t forget, you’ve got lots of networks to tap (not just those on LinkedIn) – including at SfRBM’s Annual Conference - because everybody knows somebody who knows somebody!

In part 3 of this series, Dr. Anne Diers will explore the topic “Resume ≠ Curriculum Vitae” In her series “Exploring Careers in Industry.”

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Category: Education


Exploring Careers In Industry: What do I want to be?

Part 1 of 4 on “Exploring Careers in Industry” by SfRBM Nominations/Leadership Development Chair Anne Diers, Ph.D. (Dr. Diers on LinkedIn: https://www.linkedin.com/in/annerdiers/)


This might sound obvious, but “Industry” is a really broad term – so when you think of a job in industry, you’re actually talking about many huge sectors of science.  The available jobs will be very different based on what you’re looking for.  So you need to ask yourself a few questions to narrow in on the type of position you’re interested in. Do you want to be bench-facing? Would you like to manage a group of scientists? Do you love writing about science? Do your interests lie in product development, management, pharma, bio-tech, or instrumentation? These are obviously critical questions and you have to answer them for yourself. If the answers aren’t obvious, spend some time exploring different areas of non-academic science. myIDP at Science Careers is a very helpful tool in this respect (myidp.sciencecareers.org/). In fact, there is an incredible wealth of information on Science Careers itself. Another good way to get a handle on what you're looking for is to talk to people doing these various jobs. Talk to your sales reps, see who they know and if they can connect you to people, set-up informational interviews to find out what people actually do in their jobs.

Looking at job sites for current openings can also help you refine your idea of an ideal position.  First, you’ll see what opportunities are already open.  But second, and more importantly, you’ll get an idea for what job titles match the job you want to do (and for which you have the necessary experience).  You’ll start to develop a feeling for whether or not you want to be a Field Applications Scientist, or a Program Manager, or whatever, based on those descriptions. Then, when you find yourself in conversation with your sales reps, colleagues, or faculty, you can say to them “I’m looking for an entry-level [ideal position for you]. Have you heard of any openings for this type of job at [their illustrious company]?” This instantly gives you some credibility… and rightfully so. It means that you have done your homework, and you have a real idea of what you want to do.

In part 2 of this series, Dr. Anne Diers will explore the topic “Where do I want to work… and who already works there?” In her series “Exploring Careers in Industry.”

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Categories: Education, SfRBM Trainee Council


Redox proteomics reveals overlapping mechanisms of neurodegeneration in Down syndrome and Alzheimer disease

By: Eugenio Barone and Marzia Perluigi

Read the full articles in Free Radical Biology and Medicine here: Barone E et al. Free Radic Biol Med, 111:262-269, 2017Barone E et al. Free Radic Biol Med, 114:84-93, 2018

Accumulation of oxidative damage is a common feature of neurodegeneration that, together with mitochondrial dysfunction, point to the fact that reactive oxygen species are major contributors to loss of neuronal homeostasis and cell death. Among several targets of oxidative stress, free radical-mediated damage to proteins is particularly important in aging and age-related neurodegenerative diseases. In the majority of cases, oxidative stress mediated post-translational modifications cause non-reversible modifications of protein structure that consistently lead to impaired function.

Figure: The workflow of a redox proteomics analysis is showed in six principal steps.

Redox proteomics methods are powerful tools to unravel the complexity of neurodegeneration, by identifying brain proteins with oxidative post-translational modifications that are detrimental for protein function and pathogenesis (Butterfield DA et al. Biochem J, 463:177-89, 2014). Our published studies show evidence of impaired pathways linked to oxidative stress possibly involved in the neurodegenerative process leading to the development of Alzheimer-like dementia (Di Domenico F et al. Antioxid Redox Signal, 26:364-387, 2017). Recently, we also focused on dysregulated pathways underlying neurodegeneration in aging adults with Down syndrome (DS) (Barone E et al. Free Radic Biol Med, 111:262-269, 2017). Interestingly, DS individuals by the age of 40ys are at increased risk to develop Alzheimer disease (AD) like dementia.

Results obtained by the analysis of human specimens and studies from mouse and cellular models of the disease evince a molecular link between protein oxidation/aggregation, the integrity of protein quality control system [proteasome, unfolded protein response (UPR) and autophagy], dysfunction of energy metabolism and neurodegeneration (Di Domenico F et al. Antioxid Redox Signal, 26:364-387, 2017). Many common pathological hallmarks exist between DS and AD including deposition of b-amyloid plaques, Tau-based neurofibrillary tangles, increased oxidative damage, and impaired mitochondrial function, among others. Intriguingly, we propose that all these processes seem to be joined by a “leitmotif” – oxidative stress - since they are all the cause and/or the consequence of increased free radical burden. If low amounts of reactive oxygen species (ROS) can activate the protective cellular apparatus such as the antioxidant and heat shock responses, cell cycle regulation, DNA repair, UPR and autophagy, then chronic exposure to ROS causes irreversible damage to all intracellular macromolecules (Barone E et al. Free Radic Biol Med, 111:262-269, 2017). Among these, protein oxidation impairs multiple cellular functions by a largely irreversible process that results in altered, mostly reduced, protein activity. It is likely that stressed neurons have the challenge of increasing loads of oxidatively damaged proteins, which overwhelm the ability of the proteostasis network. This, in turn, promotes further accumulation of damaged proteins, increasingly prone to aggregation, ultimately resulting in neuronal death. Alteration of protein homeostasis coupled with increasing demand for protein degradation, and reduced ATP production may produce a vicious cycle that may accelerate the neurodegenerative process (Barone E et al. Free Radic Biol Med, 111:262-269, 2017, Barone E et al. Free Radic Biol Med, 114:84-93, 2018).Therapeutic strategies aimed at preventing/reducing multiple components of processes leading to accumulation of oxidative damage will be critical in future studies.

Laboratory of Redox Biochemistry in Neuroscience, Department of Biochemistry, Sapienza University of Rome, Email: Eugenio.barone@uniroma1.it

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Category: Redox Biology


Why did the scientist cross the ocean? To get perspective from the other side.

By: Matthew Randall, Ph.D. ETH Zürich, & Niki Ubags, Ph.D., CHUV, Lausanne

Exploration is the crux of science, whether it is that of visible or invisible phenomena. Without the exploration of faraway lands, Darwin’s theory of evolution would not exist. However, today’s technology provides scientists with more information than ever, so is this type of exploration really still needed? We can explore places or accomplish many things without leaving the comfort of our home or office. So, why cross an ocean when you can simply collaborate through a video chat with scientists from around the globe? 

Image Provided By: Matthew & Niki Ubags

Crossing the ocean for research is not limited to simply acquiring data or becoming knowledgeable about a specific subject matter. By living in a different environment, different culture, language, et cetera you may find yourself starting to think differently about the world around you and the way you conduct science or think about new scientific questions. In a sense, physical exploration brings mental exploration.

            How does physically being somewhere else benefit you in your scientific career?

When you find yourself dropped into a strange new place, all of your senses become heightened and you first notice all of the differences (both cultural and social). Even the simplest of things become interesting, whereas the same things commonly encountered at home were too mundane to see from a different perspective. This outsider’s perspective is the first benefit to you. The research you would otherwise perform routinely will come into a new light and not only will others have the opportunity to help you view your projects differently, but you yourself begin to think differently. For example, a year ago I moved to Switzerland and joined a laboratory in the Institute for Biomechanics at ETH Zürich. Most of my colleagues are researching processes that range from mechanobiology signaling pathways to computer-generated simulations of bone fracture. Now, as a redox biologist, not only do I have the opportunity to discuss my research with people who approach problems in a different way, but I also begin to view my own research from this outside perspective. Moreover, I have begun to integrate their knowledge and thinking into my work and approach my questions from a very different perspective than I had before.

When you place yourself in someone else’s shoes, and begin to view things from another perspective, you may also begin to - in essence - find yourself. This active mindfulness, as I call it, is critical for navigating not only life, but also career and research. What do I want? How should I get there? These are the questions that you will find yourself asking. Stepping out of your own shoes and looking at how you navigate in a new place with new people and situations, you come to understand your own preferences as well as how you feel in certain situations. Since people in other parts of the world communicate differently about what they want and how they feel, you face the challenge to understand not only how you express yourself, but also how others express themselves toward you. The ability to know yourself as well as understand others is certainly an earned skill of working internationally.

Every country, every institution, and every lab functions differently, therefore the best way to succeed in a new place is to adapt. When you begin to see yourself as a part of the world in which you once felt foreign, you might realize that you are capable of adaptation, even on a short-time scale. You are capable of using tools and skills that you had not known how to use before. The ability to adapt to not only your physical environment but also the political and research environments of a new institution promotes your flexibility and creativity in your character as well as in your research.

Now you may be thinking… how long do I have to be abroad to become “enlightened.” It is not necessary to move abroad permanently to benefit from these experiences. In the case for Darwin, it was only after his return to England from the Galapagos, while contemplating his drawings, that he would develop his theory of evolution. In a similar way, returning home with a new perspective on your own research and life may lead to the greatest of discoveries of yourself and your career.

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