Congratulations to Jenna and Nicole who became the first two students from the lab to defend their PhDs!
1. Intracellular Protein Editing to Enable Incorporation of Non-Canonical Residues into Endogenous Proteins, J.N. Beyer, Y.V. Serebrenik, K. Toy, M.A. Najar, N.R. Raniszewski, O. Shalem* and G.M. Burslem*
Biorxiv: 10.1101/2024.07.08.602493
The first describes our intra-cellular protein editing approach to site specifically incorporate a non-canonical residue in a cell, enabling pulldowns without an antibody and the use of a small molecule fluorophore to image an endogenous protein!
2. The Interplay of Acetylation and Ubiquitination Controls PRMT1 Homeostasis, M.A. Najar, J.N. Beyer, C.M. Crawford, and G.M. Burslem
Biorxiv: 10.1101/2024.06.18.599616
The second is the first of several (watch this space) papers on the roles of lysine acetylation in protein homeostasis. We show that once acetylated, PRMT1 is recognized by the E3 ligase FBXL17, resulting in it’s ubiquitination and degradation. We applied mammalian genetic code expansion to site specifically incorporate authentic acetyl-lysine into PRMT1 to confirm our findings.
3. A selective S-acyltransferase inhibitor suppresses tumor growth J.Y. Lee, S. Dilones, T. Maujean, M. Asad, M.A. Najar, N. Auslander. D.C. Brady, G.M. Burslem* and E.S. Witze*
Biorxiv: 10.1101/2024.06.18.599616
The third reports on the discovery and optimization of the first drug like inhibitor of DHHC palmitoyl transferases. Our lead compound fully phenocopies genetic ablation of DHHC20, is orally available and improves survival in murine KRas mutant lung cancer xenografts!
Brie was awarded a HHMI Gilliam Fellowship!
https://www.hhmi.org/news/hhmi-names-50-gilliam-fellows-milestone-year
After 4 years in the lab and 4 years in the FERBS program, Amy presents here final year project!
Five ways in which rookie lab leaders can get up to speed
An array of spreadsheets, courses and online resources are available to support principal investigators leading their first research groups.
We are excited to share our new preprint in which we use the SPOTLITES platform to discover novel effectors for #targetedproteindegradation and other proximity-based approaches!
https://www.biorxiv.org/content/10.1101/2023.07.13.548759v1
After tagging 500+ members of the proteostasis network, we performed systematic recruitment of each tagged protein to a model target using a generic heterobifunctional ligand. Screening against both an endogenous and exogenous protein targets, we identified many interesting hits, including multiple members of the CTLH E3 ligase complex which we validate can be used for TPD!
This work was done in close collaboration with the Ophir Shalem Lab and builds upon their awesome endogenous tagging platform from Yevgeniy Serebrenik and Steph Sansbury– SPOTLITES (Scalable POoled Targeting with a LIgandable Tag at Endogenous Sites)
https://www.biorxiv.org/content/10.1101/2023.07.13.548611v1
George presented the labs work on Beta-peptides as conditional ligands for MHCs
Congratulations to Jenna Beyer for winning a poster prize at the recent Chemistry-Biology Interface Symposium!
Along with our Penn Therapeutic Mechanism colleagues, the lab has been awarded a NIH Director’s Transformative Research Award!
The PTM team is made up of George, Donita Brady, Terrence Gade, Luca Busino and Eric Witze and brings together expertise in translational medicine, mechanistic cell biology, and chemical biology with the goal of developing methods to quantitatively evaluate molecular features of cellular dynamics to improve diagnostics and motivate targeted therapy discovery.
Our Transformative Research Award (TR01) entitled “Unlocking the Chemical Space of Cancer-Associated Perturbations”, will create the Probe Enabled Activity Reporting (PEAR) platform technology.
PEAR leverages chemical biology, chemoproteomics, and chemical imaging approaches to profile alterations in the cancer proteome in response to therapeutic insults in patient samples as a means to predict therapeutic responses and discover unexplored liabilities.
Congratulations to Myles on an excellent poster presentation at the Penn Summer Undergraduate Internship Program (SUIP) Symposium as well as a talk at the 2022 Leadership Alliance National Symposium!
Good luck back at MIT and we hope you’ll come back next summer!
George wrote a preview piece for Cell to highlight some exciting new work from the Clausen lab on targeted protein degradation in bacteria.
TAPBPR employs a ligand-independent docking mechanism to chaperone MR1 molecules
A new paper from our friends and collaborators in Nik Sgourakis Lab defines how the chaperone TAPBPR binds to antigen-presenting MR1 molecules and facilitates loading and exchange of metabolite-derived ligands on the MR1 complex.
We’re pleased to welcome Brianna Hill-Payne to the lab!
Brie joins us as a graduate student from the Biochemistry and Molecular Biophysics Graduate Group having previously spend time in various academic and industrial labs!
The Burslem, Marmorstein and Wellen labs have been awarded an NCI R01 to support our work on ACLY
Congratulations to Jenna Beyer and Adam Green who both won prizes for their poster presentations at the recent departmental retreat!
George and Nicole both spoke at the Penn Epigenetics Institute Retreat at the Phillies Stadium and Nicole came home with a poster prize! Congratulations Nicole!
The Burslem Lab ran the 5K for the Penn Institute on Aging on Sunday Morning - Well done everyone!
We’re pleased to welcome two new lab members!
Brianna Hill-Payne joins us as a Rotation Student from the Biochemistry and Molecular Biophysics Graduate Group having previously spend time in various academic and industrial labs!
Trenton Winters joins us as a research specialist following his BS in Biochemistry from University of Notre Dame and will be working on peptide-protein interactions and keeping us all organized!
Welcome to the lab!
In this paper in RSC Medicinal Chemistry we used a catalyst free photochemical transformation to explore new chemical space for epigenetic drug discovery!
Read more here
