Organic Synthesis as a Translational and Transformational Science

Believe it or not, ever since the beginnings of human civilization, we Homo sapiens have been doing 'drug discovery'. While the earliest civilizations did not have access to the state-of-the-art science that rests today at our fingertips, all peoples have always been in the business and art of looking to nature for sources of biologically active substances that might find utility in treating human diseases. Think about it - every indigenous culture, from every continent, and every corner of the Earth (figuratively! yes, I believe the Earth is spherical) ubiquitously has developed a way of finding natural substances to treat cancer, diabetes, bacterial and viral infections... you name it.

The advent of modern scientific techniques has transformed this mysterious art of finding cures from nature to actual, physical scientific processes, and an understanding of the biological world from a molecular point of view. For the last 150+ years, chemists have become increasingly good at making, synthetically, molecules that are otherwise found in nature - and over the sands of time, the parallel advances in chemical technology, reaction development, and synthetic strategy have enabled syntheses of targets with increasingly exquisite complexity. But remarkably, while molecules isolated from nature only comprise less than four percent of chemical entities approved by the US FDA to treat human disease, over ten times as many small molecules currently approved by the FDA are derivatives of, analogs of, or mimics of natural products! (See the seminal review published by David Newman and Gordon Cragg, J. Nat Prod. 2020)

What does this suggest? How do we get from molecules from nature, to those which are inspired by nature, but vastly improved by design? Herein is the power that an organic chemist holds between their index finger and their thumb, no longer limited to what is found in nature but rather only by the limits of our imagination and ingenuity. Before us is the vast, largely unexplored space of all the possible chemical structures that could possibly exist and/or be produced in a laboratory, most with unknown and unevaluated function. This is our frontier of discovery, where the only thing that stands between where we are today and the next cure for human disease rests in the innovation of new chemistry that enables new inroads in biology and medicine, whether this be in the development of a more metabolically stable natural product, the synthesis of an ionizable lipid for an mRNA vaccine, the labeling of a bioactive peptide with a fluorophore for in vitro or in vivo optical readouts... the list could go on forever. Not only is organic chemistry relevant in medicine, it is the very heart of molecular innovation in healthcare. (For a recent review, read Maccoss, Science 2004; Boger, J. Org. Chem. 2017). "If medicine were like software, then organic chemistry is the bootcode." I am convinced that if there is a biomedical challenge out there, whether it be in developing the next vaccine for the next emergent virus, tackling invisible cancers in human cell models, or fine tuning a fluorescent label for ultra-sensitive single cell diagnostics.... these are solvable challenges in the hands and eyes of an organic chemist.

WHAT WE VALUE

Science is incredibly hard and yet ineffably rewarding. There's no doubt that to make legitimate discoveries, scientists must be ready to roll up their sleeves and spend inordinate quantities of time in the laboratory, spending day after day troubleshooting challenging scientific issues. And yet, science is incredibly rewarding when those who persevere with grit and valor come through on the other side with newfound discoveries, only made possible by those long grueling hours at the hood, an insatiable appetite for new ideas, and a rigorous work ethic that leaves no detail unturned. (See Murcko, J. Med. Chem. 2018, "What makes a great medicinal chemist?)

Therefore, the culture we hope to imbue in this group is fairly simple:

We work very, very hard. And we're proud of what we do at the end of the day, even if experiments we do to the best of our ability do not give expected results. We're ready to get to the hood, first and foremost as a training exercise, knowing that every hour spent learning how to do science better is never an hour wasted; and second of all knowing that no great discovery comes to be without the immense bravery of hardworking scientists.
We're not afraid of thinking outside of the box. This is a group that is not fixated on merely total synthesis of natural products, or on privileged scaffolds in medicinal chemistry, or on development of next-gen catalysts or computer models - we're all of the above and believe that the best organic chemists are those who are unfettered by categorical definitions. We'll do anything it takes to solve a problem.
We're convinced the best view of the world is a molecular one. Hence, we approach medicine with the mindset that organic chemistry is central to everything. We're molecule builders and molecular innovators.

MY MENTORSHIP PHILOSPHY

We are all a product of our experiences and our training. Here's a few pieces of insight I hope my students are aware of, which ultimately shapes my view towards mentorship, teaching, and training at ASDRP:

The well-being of my students is the most important thing, at the end of the day. Yes, I know science is hard, and life can be hard too (especially in high school! Yes!). I see my role in mentorship to be an advocate for my students, whose personal and professional success and whose education is my utmost priority.
Science in our laboratories exists primarily as a training tool, and secondarily as a tool of discovery. This does not mean that these two are mutually incompatible. Rather, it sets the priority in our lab for how science is tackled. Organic chemistry is really hard to master - there is no way around that.
Excellence is a learned habit. We are, they say, what we repeatedly do. Therefore, there is no better time to build habitual traits of a rigorous work ethic than here and now. We do our best on every experiment... we are perfectionists, one might say.
There are no dumb questions. In fact, science is all about learning more about what is unknown each day. I will be the first to admit that I do not know everything, and ironically, the more one learns in science, the more apparent is the vast body of knowledge that one lacks. This is the continuum of learning that every scientist is involved in, and one should never be ashamed for wanting to learn what one does not already know.
Mentorship goes beyond the bench and beyond the hood. I am here to train my students as young adults, who are ready to fearlessly face the world, armed with not only skills but confidence. I strive to be here for my students, whether they simply need training on a mass spectrometer, or whether they need career advice on what to do in college, or whether they simply need a sounding board to rant to.