2021 ICBS Young Chemical Biologist Award Winners Announced - ACS Axial

2021 ICBS Young Chemical Biologist Award Winners Announced

ACS Chemical BiologyACS Pharmacology & Translational ScienceACS Omega, and Biochemistry are proud to continue supporting the ICBS Young Chemical Biologist Award.

This award is dedicated to advancing the career development of young chemical biologists. The individuals who receive this honor are recognized annually for their impactful work within the global community.

Learn more about the 2021 ICBS Young Chemical Biologist Award Winners:

Leslie Aldrich, University of Illinois Chicago

What does winning this year’s award mean to you?

Receiving this award is such an honor! This award provides recognition for the tenacity and creativity of my group and gives me the opportunity to highlight our recent discoveries and future directions. I hope that my lecture will inspire others to dream big and to get excited about how chemical biology can impact human health.

What exciting projects are you currently working on?

A major focus of our research group is developing new small-molecule probes for challenging targets to facilitate drug discovery efforts for unmet medical needs. We are particularly interested in autophagy, a catabolic process that maintains cellular homeostasis. We are currently targeting protein-protein interactions that are important for autophagy initiation to develop inhibitors with improved selectivity that could lead to new therapeutic strategies for cancer. Autophagy can enable cancer cells to overcome stress, including hypoxia, nutrient deprivation, and chemotherapy-induced stress, to survive and progress to advanced malignancy. By selectively inhibiting autophagy in cancer patients, we could restore cancer cell sensitivity to chemotherapy and minimize off-target effects. In addition to inhibiting early-stage autophagy, we are also developing probes that modulate autophagy through different mechanisms to evaluate their effects in neurodegenerative diseases. It is possible that molecules that induce autophagic flux could restore homeostasis in these diseases and prevent neuronal cell death. Precise control of the autophagy pathway could lead to numerous applications and benefits!

What do you think is the biggest challenge currently in your area of research?

Autophagy is a challenging pathway to study due to its dual nature in disease: prevention of cell death may be beneficial in neurodegeneration but is detrimental in cancer. Also, many different targets can activate or inhibit autophagy, and identifying which targets are the most promising for therapeutic modulation can be challenging. This will require careful mechanistic assessment and in vivo evaluation of new probes to discover which mechanisms of modulation are most beneficial. Furthermore, targeting protein-protein interactions has historically been considered difficult for drug discovery and development. Recent successes, like Venetoclax, have highlighted the exciting potential of this strategy for the development of novel, selective therapies.

What would your advice be to someone just starting out in the field?

I have two pieces of general advice for starting a chemistry faculty position.

  1. Establish a supportive environment that prioritizes mental and physical health in your own life and in the lives of your trainees. This is critical for productivity, success, and happiness. I personally like to spend time running and thinking of new ideas or solutions to problems, and then I’m excited to get back to my computer and lab to further develop a hypothesis and to make plans for the critical experiments to test it.
  2. Seek out supportive mentors. It can be overwhelming setting up a new lab, teaching new classes, and training new graduate students, so it’s especially important to have a network of people who can give insightful advice and provide encouragement.

This is my advice for starting out in the chemical biology field.

  1. Take risks! Chemical Biology is highly interdisciplinary, and there are many challenging problems. There is an inherent risk to tackling any challenging problem, but as a chemical biologist, you have a diverse skillset that lends itself to devising creative solutions.
  2. Collaborate! Working with talented, supportive collaborators to design experiments, analyze results, and discuss future directions can really advance your research and lead to new discoveries and ideas due to diverse experiences and viewpoints.

What advances do you hope to see in your field over the next decade?

I hope to continue seeing advances in the determination of mechanisms of small-molecule probes discovered through phenotypic screening and the evaluation of selectivity of probes for non-traditional targets. I also hope to see new and exciting approaches to developing small-molecule tools to modulate complex cellular pathways, and I look forward to the new knowledge we will gain from analyzing the results of selective pathway modulation in basic biology and human disease. Finally, I hope to see a continual push for improving diversity, equity, and inclusion in our field, because all people and voices are needed to realize the discoveries of the future.

Read Leslie Aldrich’s contributions to the field through their ACS published research.

Jeremy Baskin, Cornell University

What does winning this year’s award mean to you?

Above all, this award is a recognition of the contributions of a creative and dedicated team of students and postdoctoral scholars working in my lab, and I am so grateful for their innovative ideas, their passion for research, and for pushing me to become a better scientist and mentor. Additionally, this award is a recognition that lipids and membranes are currently, and will hopefully remain for many years, a fertile area for investigation at the chemistry–biology interface.

What exciting projects are you currently working on?

We are excited to apply our tools to frontier questions in lipid biology. Two examples: How do cells maintain the non-equilibrium localization of lipids in specific membranes? We are working on projects to define the rules of lipid transport between organelles and across bilayers. How do cells regulate the production and consumption of bioactive signaling lipids? Their chemical structures and the enzymes that produce them have mostly been identified, but the factors that regulate their activity are not well understood in many instances, and we are combining our labeling tools with CRISPR screening to discover new regulatory networks.

What do you think is the biggest challenge currently in your area of research?

Unlike proteins, lipids are not directly genetically encoded but are instead the products of a complex and interconnected metabolic network. Much of the challenge of studying lipids and membranes stems from this metabolic complexity and therefore motivates the development of precision tools for visualization and manipulation of lipid production and metabolic flux.

What would your advice be to someone just starting out in the field?

I would advise newcomers to identify a niche where there are important questions. The questions don’t have to be new, but one should strive to bring something new to address the questions in a different way. Even for tool-builders, being question-focused can increase the impact of your advances. The other piece of advice is to pick one’s mentors carefully and surround oneself with a good support system of mentors and collaborators.

What advances do you hope to see in your field over the next decade?

Broadly, I hope to see more complete molecular descriptions of the fascinating and complicated phenomena of lipid transport and homeostasis. I would love to increase connections at the chemistry–biology interface, which is a two-way street: more biologists adopting chemical tools and adopting a chemically oriented mindset, and more chemists gaining a deeper appreciation of the complexity of cellular systems and pushing methods advances toward important applications in biology.

Read Jeremy Baskin’s contributions to the field through their ACS published research.

Nir London, Weizmann Institute of Science

What does winning this year’s award mean to you?

I’m deeply honored and proud to receive this award. As someone who started his career strictly as a computational scientist and have only transitioned into experimental chemical biology as I started my independent career here at the Weizmann Institute, this recognition means a lot to me. The chemical biology community is awesome, friendly and collegial and I’m very happy to be accepted into the fold.

What exciting projects are you currently working on?

A big part of our lab is focused now on our recently published “CoLDR”(covalent ligand directed release) chemistry. This technology allows to both functionalize targeted covalent inhibitors, as well as to site-specifically label target proteins in live cells. We are now developing new applications for this chemistry in the domains of targeted protein degradation and protein proximity inducers in general.

Another project that we are still very much involved with is the COVID moonshot – an ambitious open-science initiative I co-founded with several like-minded scientists early in 2020. We aim to develop a safe and cheap therapeutic against SARS-CoV-2 (targeting the Main Protease) through a combination of crowdsourcing and structure based-design. Recently we were awarded a grant by the Wellcome Trust that should enable us to advance compounds to pre-clinical testing and hopefully to IND.

What do you think is the biggest challenge currently in your area of research?

I think one of the biggest challenges in the field of covalent inhibitors, which is heavily studied nowadays, is the discovery of new covalent ‘warheads’ against amino acids other than Cysteine, that are both sufficiently selective and stable, as well as suitable for in vivo administration.

What would your advice be to someone just starting out in the field?

I would first advise them not to listen to conventional wisdom in their field. Some of our most influential discoveries were made through ‘ignorance’ of what should or shouldn’t work. That said, my next best advice is to find your community and build your network of mentors, collaborators, friends and colleagues. This is so important, both scientifically, and psychologically, and I think is sometimes under appreciated by young researchers.

What advances do you hope to see in your field over the next decade?

Targeted covalent inhibitors are already becoming mainstream in drug discovery (this is very far from where they were when I got into the field and they still have some way to go). Yet, there are still very few electrophiles that are precedented in approved drugs. I hope over the next decade to see new electrophiles make it into approved drugs, expanding the scope of covalent inhibitors.

Read Nir London’s contributions to the field through their ACS published research.

Learn about winners of previous ICBS Rising Star awards, supported by ACS Publications.

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