The lab welcomes Dr. Nicholas Struntz, a chemical biology postdoc who comes to us from the Harki lab and the department of Medicinal Chemistry at the University of Minnesota. Nick is working on mechanism of action studies focused around a small molecule that binds to Max and identifying and evaluating context-specific Myc interactions. We also welcome Dr. David Freeman, a chemical biology postdoc who comes to us from the U.S. Army’s Public Health Command-Central located at JBSA Ft. Sam Houston in San Antonio Texas. David completed his PhD studies in organic chemistry at Colorado State University where he studied welwitindolinone alkaloid natural products under the guidance of Professor John Wood. David is interested in the use of small molecules to probe transcription factors in prostate cancer and adenoid cystic carcinoma.
The lab welcomes Rob Wilson, a graduate student in Biological Engineering at MIT. Rob joins us from Purdue University, where he studied biochemistry and worked on developing peptide probes for tyrosine kinase activity. He will be working on novel approaches to attenuate oncogenic Ras signaling, and is also interested in chemical modulation of protein stability.
Congratulations to Andrew Chen, who recently won the Wishnok Prize for the Bioengineering and Toxicology Seminar (BATS)! The prize is awarded for the best talks in the Fall and Spring semesters, and is given in honor of Pete Wishnok, who led BATS for decades. Congratulations, Andrew!!
Congratulations to Dr. Koehler, Francisco Caballero, and Eric Stefan, who were awarded a grant from MIT's Deshpande Center for Technical Innovation for their work on the c-Myc oncoprotein! The Deshpande Center awards grants which fund proof-of-concept studies, and validation for emerging technologies. The team has identified small molecules that bind to c-Myc containing complexes, and a smaller subset that modulate c-Myc function in cells, including c-Myc mediated transcription. The project will explore the therapeutic potential of these small molecule binders.
The lab welcomes Dr. Helen Evans, a synthetic chemistry postdoc who comes to us from the Ritter Lab and the Department of Chemistry and Chemical Biology at Harvard. Helen is working on medicinal chemistry related to small molecules that modulate deregulated transcription in prostate cancer, with emphasis on natural products. We also welcome Thijs Wildschut, a visiting Master's student from Utrecht University. Thijs is part of a program focused on cancer, stem cells, and developmental biology, making him a perfect fit for our team focused on Myc-mediated transcription. Finally, we welcome another young member, Arabella Josefine Vegas, born on July 24th. Little Arabella is letting mom work on grant applications and lecture materials for 20.320 over the summer and steering clear of her toddler brothers Nico and Max.
Arabella Josefine Vegas
The past few decades have seen tremendous strides in our understanding of cancer biology, but the translation of that knowledge into actionable information for cancer therapy is slow in several areas. In the Koehler lab, we seek to bridge this gap in the area of oncogenic transcription factors. These proteins that initiate transcriptional programs are often mutated or unregulated in cancer settings, but have been deemed “undruggable” by conventional drug discovery methods. Practically, our focus is on the discovery of small molecule probes for modulating transcription factors implicated in cancer using our small molecule microarray (SMM) technology.
During the recent KI Open House as part of the Cambridge Science Festival, we had the opportunity to illustrate this complex idea for young visitors. At our lab’s interactive exhibit, we drew inspiration from Marvel Comics and developed a display that juxtaposed oncogenic transcription factors in two different states: as “good citizen” proteins, under normal conditions, and as “hulked-out” proteins in their cancer-causing state. Our booth featured an interactive macro-model of our SMM technology, which mimicked our probe-discovery process as a ring toss game. We asked students how to calm the hulk down, and challenged them to find a molecule that “fit” with our pipe cleaner protein. With more than 300 attending the event throughout the day, we are confident that at least a few more “small molecule detectives” are on the case!
Welcome Shelby Pursley, a graduate student in Biological Engineering at MIT. Shelby joins us from Louisiana State University, where she worked on gamete cryopreservation in microfluidic devices. She will be joining an expanding team working on targeting oncogenic transcription factors, and is more specifically interested in exploring natural products, FDA approved drugs, and using novel compounds in combination for the treatment of prostate cancer.
Welcome to Dr. Qiaoyi Wang, Dr. Chuan-Xu Liu and Becky Leifer as new group members. Qiaoyi comes to MIT from Professor Shi's lab at WVU where he worked on novel chemistry involving gold-catalyzed reactions. Qiaoyi is joining our Myc project team and has an interest in biological target identification for natural products that modulate transcription. Chuan-Xu is a physician-scientist with expertise in mechanisms of leukemogenesis and a former trainee of Chancellor Guo-Qiang Chen at Shanghai Jiao Tong University School of Medicine. He is a recent recipient of a Milstein Medical Asian American Partnership Foundation fellowship. The fellowship will help to fund his research focused on developing new tools to modulate an oncogenic transcriptional regulator in acute myeloid leukemia known as AML1-ETO. Finally, Becky will join an expanding team in the area of modulating transcriptional processes in prostate cancer.
Welcome Megan Berry and Rob Wilson as summer research interns! Megan is working with the Myc team and Rob is working on CETSA assays in an effort to demonstrate target engagement in cells for a Class II HDAC inhibitor.
Congratulations to Marius Pop on his new paper describing our efforts to target the oncoprotein ETV1 in Molecular Cancer Therapeutics! This collaborative project involving investigators at the Koch Institute, DFCI and the Broad Institute provided preliminary results for a new project focused on targeting deregulated transcription factors in prostate cancer. This project is part of the Transcend Partnership between KI and Janssen Pharmaceuticals, Inc.
The Koehler lab has officially moved from labs in the Broad Institute to labs across the street in the Koch Institute. We are open for science!
Andrew testing out the new water system
We also welcome Dr. Eric Stefan to the lab for postdoctoral studies! Eric completed his PhD studies in organic chemistry at University of Notre Dame under the guidance of Professor Richard Taylor. His thesis focused on novel access to methyl-substituted polyketide structural units through 1,5-hydride shift and ether transfer. Eric also worked on the synthesis of chiral fragment molecules for high-throughput screening at the Broad Institute prior to moving to MIT. Eric joins project teams focused on developing novel modulators of oncogenic transcription factors.
The Koehler lab welcomed several new members at the start of the year, including two new students and a couple of babies.
Andrew Chen, a graduate student in the Department of Biological Engineering, joins us from Cornell University’s undergraduate program in Biological Engineering. Andrew will be working on novel approaches to targeting Myc-associated transcriptional complexes. Prior to MIT, Andrew spent time as a Research Scientist at Bristol-Myers Squibb.
Rohit Thummalapali, an MD student in the Harvard-MIT Health Sciences and Technology program, comes to us from Yale University where his studies focused on Molecular Biophysics and Biochemistry. Rohit has joined a collaborative project involving the Bernstein and Suva labs at MGH aimed at developing probes for a core transcription factor network and chromatin-modifying enzymes involved in epigenetic reprogramming of glioblastoma cancer stem cells.
Finally, we welcome our two youngest members of the group, Nico Emmerich Sandoval Vegas and Maximo Aaron Torrealba Vegas. Angela delivered Nico and Max on January 22nd. The boys keep mom busy and occasionally make appearances at the Koch in their double stroller.
Nico and Maximo