How did you get interested in Medicinal Chemistry?
I became interested in medicinal chemistry during my undergraduate studies in Biotechnology (National University of Rosario, Argentina), where I was fascinated by the potential for chemistry to address important problems in healthcare. As I learned more about the role of chemistry in drug discovery and development, I became increasingly interested in the interdisciplinary nature of medicinal chemistry and the potential for collaboration between chemists, biologists, and clinicians to develop new therapies.
My passion for medicinal chemistry continued to grow during my graduate studies, where I had the opportunity to work on a project focused on the design and synthesis of novel small molecules for the treatment of neglected tropical diseases (NTDs), such as leishmaniasis, Chagas disease, HAT, malaria, etc., as well as for cancer. This experience solidified my interest in drug discovery and showed me the potential impact that medicinal chemistry research can have on patients' lives.
Since then, I have been fortunate to have the opportunity to work on a range of projects in medicinal chemistry and chemical biology, from designing inhibitors of infectious disease targets to developing novel chemical probes for target discovery in NTDs. The diversity of these projects has allowed me to develop a broad perspective on the field and has reinforced my passion for using chemistry to address important problems in healthcare.
What was the topic of your PhD project?
My interest in prenylated compounds, a privileged structure in nature, together with the enormous experience of my supervisor in the prenylated’s world, Prof Guillermo Labadie, led me to pursue a PhD focused on using these compounds as a basis for generating novel chemical and biological tools to expand our understanding of foundational biology, particularly regarding organisms that produce neglected tropical diseases (NTDs). Through my research, I aimed to develop new strategies for identifying and targeting NTD-producing organisms, which pose a significant public health threat in many parts of the world.
My PhD thesis was completed in 2015 at National University of Rosario, and was recognized and awarded by the Argentine Society of Organic Chemistry as the best Argentine thesis of the biennium (2015-2016). This recognition was a testament to the innovative approach and significant contributions of my research, which has the potential to drive new discoveries in the field of medicinal chemistry.
My first postdoctoral experience was in Argentina, working at the Rosario Chemistry Institute and the Institute of Molecular and Cellular Biology of Rosario. My second postdoctoral position was at the Department of Chemistry of Durham University, in the United Kingdom.
Where are you currently working and are your current research interests?
Currently, I am working at Durham University (United Kingdom) as a Research Fellow (Marie Skodowska–Curie actions, Durham University, and the Network for Neglected Tropical Diseases).
My current research interests focus on the use of activity-based protein profiling (ABPP) to develop new strategies for identifying and targeting enzymes involved in the pathogenesis of neglected tropical diseases (NTDs). ABPP is a powerful chemoproteomic tool that allows us to selectively visualize and measure the activity of enzymes within complex biological systems, providing valuable insights into the mechanisms underlying disease.
My research in this area aims to expand our understanding of the molecular mechanisms driving NTD pathogenesis, with the ultimate goal of identifying new therapeutic targets and developing more effective treatments for these devastating diseases. I am particularly interested in exploring the use of ABPP in combination with other technologies, such as high-throughput screening and medicinal chemistry, to accelerate the discovery and development of new drugs for NTDs.
How would you explain what your research area is to non-scientists?
My research area focuses on studying diseases that are often overlooked and underfunded, called neglected tropical diseases (NTDs). These diseases affect more than 1 billion of people in low-income countries and can cause a lot of suffering and disability.
To help find better treatments for NTDs, I use a special technique called activity-based protein profiling (ABPP), which allows me to study the specific proteins in the pathogens that are involved in causing these diseases. By understanding how these proteins work and interact with each other (this is called the interactome), we can identify new ways to stop the disease from progressing and develop more effective drugs.
To help explain my research approach, I often use the analogy of archery. Just as an archer uses a bow and arrow to hit a target, I use specialized techniques and chemical probes to study proteins in the body that are involved in disease. In this analogy, the bow represents the various techniques I use, such as activity-based protein profiling (ABPP), while the arrow represents the chemical probes that I use to target specific proteins of interest. The target itself represents the sum of all the proteins in an organism, and the centre of the target is the specific proteins that I want to study. Just as an archer aims for the centre of the target, I aim to use my techniques and chemical probes to study the proteins that are most relevant to disease. By hitting these targets, I can gain a better understanding of the mechanisms behind disease and identify new ways to develop more effective treatments.
What do you like best about your work?
As many scientists in the field of medicinal chemistry, I enjoy the opportunity to make a meaningful impact on human health by developing new treatments for diseases that can have a major impact on people's lives. This sense of purpose and contribution to society can be incredibly rewarding.
Additionally, I enjoy the intellectual challenge and creativity that comes with designing new chemical compounds and developing innovative approaches to studying disease. There is always more to learn and discover in this field, which can make for a stimulating and engaging work environment. Also, I am grateful for the collaborative nature of the work, which often involves working with other scientists and researchers across different disciplines to tackle complex problems. The opportunity to work with others who are passionate about advancing scientific knowledge can be a fulfilling and motivating experience.
Of course, collaborating with other scientists and networking is also critical to successful research in this field. Finally, writing reports and publications and supervising PhD and Master students are important aspects of communicating research findings and mentoring the next generation of scientists.
What do you consider your greatest achievement in your scientific career?
It can be difficult to pinpoint a single greatest achievement in my scientific career. While I have received individual awards that I am proud of, I would say that one of the most fulfilling experiences was the day my first master's student, Dr. Jaime Isern, obtained his degree. Being able to train and mentor the next generation of scientists is incredibly inspiring and rewarding. It's exciting to see my students grow and develop their own research interests, and I feel a sense of pride and satisfaction in their accomplishments. Ultimately, they will carry on the work and push the boundaries of scientific discovery even further, and I am honoured to have played a part in their journey.
Which of your papers are you most proud of and why?
One of the papers that I am most proud of is "Discovery of Leishmania Druggable Serine Proteases by Activity-Based Protein Profiling," which was published in Frontiers in Pharmacology in 2022. This paper is particularly meaningful to me because it represents the first of a series of publications that will highlight the use of chemoproteomic tools in NTD-producing parasites, a project that I am currently leading at Durham University. Through this research, we are exploring new ways to identify and target the proteins that are responsible for causing diseases like leishmaniasis, and I am excited about the potential impact that our work could have on global health.
Porta, E.O.J., Isern, J.A., Kalesh, K., Steel, P.G. 2022. Discovery of Leishmania Druggable Serine Proteases by Activity-Based Protein Profiling. Front Pharmacol. 13, 929493. doi: 10.3389/fphar.2022.929493.
What are the features of a successful PhD student or postdoc?
PhD students and postdocs need to be self-motivated and have a strong work ethic to be successful. They need to be able to work independently and manage their time effectively. Another key feature is critical thinking and problem-solving skills, adaptability, and resilience. Also, a clear communication of ideas, results, and challenges is essential to succeed as a PhD student or postdoc. PhD students and postdocs often work as part of a larger research group, so the ability to work effectively in a team is critical for the sharing of ideas, knowledge, and resources to accomplish research goals. Finally, a love for science and a genuine curiosity about the world are key ingredients for success in a PhD program or postdoc position.
What advice would you give to someone who wants to know more about your field?
If someone wants to know more about my field, I would suggest several things: Start by reading review articles and textbooks on medicinal chemistry to gain a solid foundation of the field's principles and techniques. Attend conferences, workshops, and seminars to learn about the latest research and network with other scientists. Consider pursuing an internship or research experience in a medicinal chemistry lab to gain hands-on experience with the techniques and methods used in the field. Join professional organizations and subscribe to relevant journals to stay up-to-date on the latest research and news in the field. Finally, be curious and ask questions! The field of medicinal chemistry is constantly evolving, and there is always something new to learn.
Have you experienced any unfair situations during your scientific career? How would you advise scientists facing similar situations?
Unfortunately, unfair situations can occur in any career, including scientific research. However, if a scientist is facing an unfair situation, my advice would be to first seek support from colleagues or mentors or institutional resource, and document the situation as much as possible. It may also be helpful to reach out to relevant professional organizations or advocacy groups for guidance and resources. It is important to remember that addressing unfair situations can take time and persistence, but seeking help and speaking out can ultimately lead to positive change. I have personally witnessed and experienced unfair situations in my scientific career, and I believe it is important to seek guidance and support in such situations.
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
When I first started working in a laboratory, in my very first day, I accidentally broke a mortar. But it taught me a valuable lesson - that mistakes and accidents are an inherent part of the scientific process and that it's often through failure that we learn the most. As a result, I've always believed that if you're not breaking something in the lab, you're probably not pushing the boundaries of what's possible.
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
Films: Radioactive; Breaking bad (series); Perfume, the Story of a Murderer.
Books: The Disappearing Spoon: And Other True Tales of Madness, Love, and the History of the World from the Periodic Table of the Elements by Sam Kean; H2O: A Biography of Water by Phillip Ball; Vector by Robin Cook.
Which scientist do you admire the most and why?
There are many scientists who have made significant contributions to the field of medicinal chemistry, and it is difficult to choose just one. However, if I had to pick, I would say Carolyn Bertozzi, because she is a renowned chemist and biochemist who has made significant contributions to the fields of chemical biology and glycobiology. I admire her not only for her ground-breaking research but also for her commitment to promoting diversity and inclusion in science. As a leader in her field, she has inspired many young scientists to pursue careers in STEM and has worked to create opportunities for underrepresented groups in academia. Her dedication to interdisciplinary research and her ability to combine chemistry, biology, and medicine in innovative ways is truly remarkable, and I am inspired by her work and her vision for the future of science.
Which field of medicinal chemistry do you consider the most promising for the future?
Currently, there are several exciting areas in medicinal chemistry that show great potential for future developments. Some of the most promising fields of medicinal chemistry for the future include the development of targeted therapies for cancer and other diseases, the discovery of novel antibiotics and antiviral drugs to combat emerging infectious diseases, the design of new drugs for neurological disorders, proteolysis targeting chimera (PROTAC), nanotechnology-based drug delivery systems, and the development of personalized medicine approaches based on genomics and proteomics. They are all promising areas that could have a significant impact on human health in the future. Additionally, the use of artificial intelligence and machine learning in medicinal chemistry is also a rapidly growing area that holds great promise for accelerating drug discovery and development.
What would you expect to be the next major breakthrough in medicinal chemistry?
I would say that personalized medicine is one the most promising area in medicinal chemistry and, possibly, the next major breakthrough. Recent advances in genomics, proteomics, and related fields are making it possible to tailor treatments to an individual's specific genetic and disease profile. This will be further accelerated by the integration of artificial intelligence into medical development programs, which can help identify personalized treatment options based on large-scale data analysis.
