Goodbye and good luck!

As we happily say goodbye to 2020, we want to say goodbye and good luck! to several lab members who moved on to new positions this year. Best of luck to these former members: Dr. Brice Curtin now at Dicerna Pharmaceuticals, Dr. Nick Struntz now at GlaxoSmithKline, Dr. Yulong Su now in China, and Dr. Shelby Doyle now at MIT’s Center for Microbiome Informatics and Therapeutics.

Despite the ongoing pandemic, the Koehler lab will be looking to say hello to some new faces in 2021. The new year will bring training opportunities to advance defined, funded projects in probe discovery for tough targets. Potential postdoctoral candidates with backgrounds in cancer biology, transcription, biochemistry, synthetic chemistry, chemical biology should reach out directly to Professor Koehler at koehler@mit.edu.

Until then, again, we’ll say goodbye 2020! And we hope you enjoy a healthy and hopeful holiday season.

New paper out in Cell Chemical Biology!

We are thrilled to share a story emerging from our androgen receptor program is now available for download at Cell Chemical Biology!

This work, co-led by Dr. Andre Richters and Dr. Shelby Doyle, has been a long-running effort from our team focused on prostate cancer, who discovered KI-ARv-03, a selective CDK9 inhibitor with potent activity in castration resistant prostate cancer models. The initial discovery was supported through a partnership with Janssen Pharmaceuticals and validated in collaboration with the lab of Dr. Steven Balk through the Koch Institute and Dana-Farber/Harvard Cancer Center (DF/HCC) Bridge Project. More recently this project grew to collaborative effort between our lab, colleagues at the Therapeutic Innovation Center at Baylor College of Medicine, and Kronos Bio, Inc., who optimized KI-ARv-03 to produce KB-0742.

We are grateful to the entire team of authors and extend congratulations to all!

REFERENCE: *André Richters, *Shelby K. Doyle, David B. Freeman, Christina Lee, Becky S. Leifer, Sajjeev Jagannathan, Florian Kabinger, Jošt Vrabič Koren, Nicholas B. Struntz, Julie Urgiles, Ryan A. Stagg, Brice H. Curtin, Deep Chatterjee, Sebastian Mathea, Peter J. Mikochik, Tamara D. Hopkins, Hua Gao, Jonathan Branch, Hong Xin, Lori Westover, Gilles C. Bignan, Brent A. Rupnow, Kristen L. Karlin, Calla M. Olson, Thomas F. Westbrook, Joseph Vacca, Chris M. Wilfong, B. Wesley Trotter, Douglas C. Saffran, Norbert Bischofberger, Stefan Knapp, Joshua W. Russo, Ian Hickson, James R. Bischoff, Marco M. Gottardis, Steven P. Balk, Charles Y. Lin, Marius S. Pop, Angela N. Koehler. “Modulating Androgen Receptor-Driven Transcription in Prostate Cancer with Selective CDK9 Inhibitors.” Cell Chemical Biology. Open Access Published: October 20, 2020 DOI:https://doi.org/10.1016/j.chembiol.2020.10.001

Congratulations, Mo and Jasmin!

We are proud to announce that Mohammed Toure and Dr. Jasmin Krüll have both received fellowships to support their academic training and scientific projects.

Mohammed, a Biological Engineering graduate student, has received the Ludwig Center at MIT's Koch Institute Graduate Fellowship to support his exploration of KI-ARV-03 derivatives in metastatic cancer models.

image from ki.mit.edu

Jasmin, a Postdoctoral Fellow with a background in chemistry, has been selected for the Walter Benjamin Programme, a two year postdoctoral fellowship program funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG). In addition to this honor, she has also been selected for the Convergence Scholars Program at the Koch Institute, where she will receive additional professional development and leadership training.

Congratulations, both—well done!

New paper out in ACS Chemical Biology!

We are excited to share that our collaborative effort to discover chemical probes for the cytokine IL-4 is now available for download at ACS Chemical Biology!

This work led by our collaborators in the laboratory of Dr. Arturo Vegas at Boston University was championed in our lab throughout the project’s lifetime by Becky Leifer. The newly published story describes the discovery and validation of the first known small molecule inhibitor of IL-4.

We extend congratulations to all involved!

Sean P. Quinnell, Becky S. Leifer, Stephen T. Nestor, Kelly Tan, Daniel F. Sheehy, Luke Ceo, Shelby K. Doyle, Angela N. Koehler, and Arturo J. Vegas. “A Small-Molecule Inhibitor to the Cytokine Interleukin-4.” ACS Chemical Biology 2020 15 (10), 2649-2654

Welcome, Maddy!

An overdue, official welcome to Dr. Maddy Henley!

Dr. Henley received her PhD in in chemical biology from University of Michigan earlier this year. Her thesis work conducted under Dr. Anna Mapp applied an array of biophysical techniques to understand the mechanisms governing the structurally heterogeneous protein-protein interactions between transcriptional activators and coactivators. She will be joining our FUSONC team, where her knowledge of organic chemistry, biology and biophysical techniques will be instrumental to developing new probes for a variety of transcriptional targets in pediatric rhabdomyosarcoma.

After a disrupted start to the year, Maddy successfully joined our team in the work-from-home world and is now fully integrated into our on site team. Welcome, Maddy!

Welcome to all of our new faces!

In the new year, the Koehler lab is very pleased to be off to the races with many new faces added to our team in the past few months.

A formal welcome to Brandon Ng and Lenya Duong, two undergraduate students joining the RNA-binding protein team with our senior graduate student, Rob, and to Will Walker, our new research associate managing our SMM platform.

And a hearty welcome back to Jasmin Krüll, a former visiting graduate student now back at as a post-doc, and to Mo Toure, a former Harvard undergraduate student researcher now back as a graduate student in the MIT BE program.

Welcome all! We’re excited to have you and to get to work!

Congratulations Dr. Doyle!

Our wonderful Shelby Doyle became the second graduate student in the lab from the Department of Biological Engineering at MIT to successfully defend her thesis, just in time for the well-earned holiday break in December of 2019!

Dr. Doyle’s thesis, entitled Modulating Oncogenic Transcription with Small Molecules, was a tour de force and emphasized various strategies to tackle AR-driven transcriptional programs. Keep an eye out for upcoming publications related to her thesis work around a selective CDK9 inhibitor and a chemical probe of the OXPHOS pathway! The lab is so proud of your accomplishments!

Shelby and Family relaxing after a job well done!

Taking a Moonshot at a rare pediatric cancer

The Koehler lab is proud to join a collaborative team involving investigators at Duke University, the Broad Institute, the National Cancer Institute, and the University of Zurich with the goal of developing tools to inform therapeutics for fusion-positive alveolar rhabsomyosarcoma. This effort is generously funded via the NCI Cancer Moonshot Initiative. You can read more about our efforts here: https://news.mit.edu/2019/taking-moonshot-rare-childhood-cancer-arms-1120