Biomedical Sciences Announcements
Department News
Kudos to Dr. Andres Blanco’s Lab and Dr. Yang Shi’s Lab (Ludwig Institute for Cancer Research) on their recent publication in Nature!
Perturbing LSD1 and WNT rewires transcription to synergistically induce AML differentiation
Acute myeloid leukemia (AML) is characterized by differentiation arrest, in which leukemic blasts fail to mature and maintain high proliferative capacity. Differentiation therapy, which aims to treat AML by de-repressing latent myeloid maturation programs to halt proliferation, is curative in the promyelocytic (APL) AML subtype but not others. Inhibitors of chromatin factors such as the histone demethylase LSD1 can induce partial differentiation in non-APL AML, but have failed to induce therapeutic levels of differentiation in clinical trials. In this study, Hosseini et al. utilized a high-throughput screening strategy to identify small molecule inhibitors that synergize with inhibitors of the histone demethylase LSD1 to induce terminal differentiation of acute myeloid leukemia cells. The authors found that combinatorial inhibition glycogen synthase kinase 3 (GSK-3) and LSD1 synergistically induces terminal differentiation in non-APL AML cell lines, patient samples, and mouse models. Mechanistically, it was found that, B-catenin – which is stabilized by GSK-3 inhibition – surprisingly does not activate the WNT pathway, but instead complexes with alternative transcription factors to carry out a pro-differentiation interferon response that is initiated by LSD1 inhibition. In pre-clinical mouse models, combinatorial treatment with LSD1 and GSK-3 inhibitors dramatically extended lifespan of AMLs with DNMT3A mutations. These findings nominate this inhibitor combination for the treatment of human non-APL AML.
Read the entire article here: https://www.nature.com/articles/s41586-025-08915-1
Congratulations are in order for Drs. Jeremy Wang and Nancy Gartland on their SAVMA Teaching Awards!
Dr. Wang was voted best lecturer and Dr. Gartland was voted best lab instructor by the First Year class!!!
Anguera Lab
Congratulations to the Anguera lab on their recent review article The conneXion between sex and immune responses published in Nature Reviews Immunology. It also made the cover!!
Dr. Kotaro Sasaki
Dr. Kotaro Sasaki has been promoted to Associate Professor with Tenure as of July 1, 2024. Kotaro is also the recipient of an endowed professorship. He is named the Richard King Mellon Associate Professor of Germ Cell Development in the Department of Biomedical Sciences.
Dr. Andrew Modzelewski
Congratulations to Dr. Andrew Modzelewski and lab on their new confirmed R35 grant.
Elaine Redding Brinster Prize Ceremony and Ralph L. Brinster Symposium
The third Annual Elaine Redding Brinster Prize Ceremony and Ralph L. Brinster Symposium was held on Wednesday, March 13, 2024.
The Symposium was held at the Smilow Center for Translational Research and hosted by the Penn Institute for Regenerative Medicine. The Elaine Redding Brinster Prize in Science or Medicine recognizes foundational discoveries in the fields of biological science and medicine. The Prize is awarded annually to an individual from any country to recognize their outstanding discovery for its unique impact on biomedicine.
Dr. Stuart H. Orkin, MD of Harvard Medical School was honored this year for his landmark discoveries of the molecular basis of blood disorders and gene regulatory mechanisms governing blood cell development.
The Elaine Redding Brinster Prize and Ralph L. Brinster Symposium are generously funded by endowments provided by the children of Elaine Redding Brinster and Dr. Ralph Brinster.
These images are courtesy of photographer, Daniel Burke.
Grant Highlight
Dr. M. Andres Blanco has been awarded a grant from the Margaret Q. Landenberger Research Foundation, in the amount of $200,000 over two years to study “Investigating the role of KAT6A as a differentiation therapy target MLL-rearranged acute myeloid leukemia”.
This project builds on our previous work that uncovered the histone acetyltransferase KAT6A and the histone binding protein ENL as drivers of transcriptional programs sustaining the stemness and proliferation of acute myeloid leukemia (AML) cells. The overall goal of the funded project is to understand the molecular mechanisms by which KAT6A and ENL cooperatively establish and maintain oncogene promoters in highly activate states. Our findings will advance the understanding of how leukemogenic gene expression programs are orchestrated, and will also help determine the contexts in which small molecule inhibition of KAT6A and/or ENL could serve as a potential therapeutic strategy in AML.
Contact the Biomedical Sciences Department
Our department is supported by a core of dedicated professional and administrative staff.
Department of Biomedical Sciences
216E Old Vet Quad
3800 Spruce Street
Philadelphia, PA 19104