Date-Time : Wednesday, March 02, 2022 15:30
***This is an online event. To obtain Zoom link and password, please contact to the department.
Murat Alper Cevher, PhD
Bilkent University, Department of Molecular Biology and Genetics
“Reconstitution of the 30-subunit human Mediator and investigation of its subunits for the potential diagnosis, prognosis and treatment of cancer.”
Mediator is a large (2 MDa) multi-modular, 30-subunit transcriptional coactivator complex that is essential for the regulation of most (if not all) protein-coding genes. It exerts this function by forming a bridge between enhancer-bound activators and promoter-bound transcription factors. While the head and middle modules of the Mediator form the active core that is responsible for interactions with promoter-bound RNA polymerase II (Pol II) and general initiation factors, the non-conserved tail module subunits are critical for interactions with enhancer-bound activators. This makes tail subunits highly desirable targets for selective gene regulation.
To facilitate functional and mechanistic studies of the Mediator, we have undertaken its reconstitution with recombinantly generated subunits. This allows assignments of novel functions to specific subunits/modules as well as analysis of their roles in various disease models for possible diagnosis, prognosis and treatment. In reconstitution studies to date, we have: (1) identified a minimal 15-subunit core that carries out effector functions at the promoter, (2) identified MED14 as the only Mediator subunit that directly interacts with Pol II to enhance its function, (3) identified a novel targetable Mediator subunit that strongly interacts with estrogen receptor alpha, (4) discovered dramatic and previously unrecognized differential expression patterns of tail module subunits both in colorectal cancer (CRC) tissues and in cell lines, (5) most importantly, discovered and pinpointed an interaction interphase between AML/ETO and the Mediator complex which will potentially allow us to design therapeutics that may benefit patients with acute myeloid leukemia. Collectively, our Mediator reconstitution tool helped us identify novel targets towards various cancer types.
Dr. Murat Alper Cevher completed his undergraduate studies at Hunter College of the City University of New York (CUNY) in 2004. Later he joined the CUNY Biochemistry Ph.D. program and earned his doctoral degree in 2009. Between 2010 and 2015 he carried out his postdoctoral work at The Rockefeller University, in the laboratory of Dr. Robert G. Roeder, a pioneer in the field of transcription. Since September 2015, Dr. Cevher has been an Assistant Professor in the Department of Molecular Biology and Genetics at Bilkent University, Ankara, as well as a guest investigator, adjunct faculty and a visiting assistant professor at The Rockefeller University.
Dr. Cevher is the recipient of numerous research grants that include an American Cancer Society postdoctoral fellowship (2013), an EMBO Installation Grant (2017), an EMBO small grant (2018), an EMBO workshop grant (2018), an EPIC XS (2019), two TUBITAK 1001 (2019, 2021) grants and an award for visiting assistant professorship at the Rockefeller University. Using the Multibac baculovirus expression system, Dr. Cevher recently reconstituted and purified the 15-subunit functional human core Mediator, which is thus far the largest protein complex so generated. The Mediator is known to be the most critical coactivator complex for enhancer-bound transcription factors. Using biochemical, structural and cell-based approaches, he and his team now work on the architectural/functional characterization of the human Mediator in the context of diseases.
All interested are cordially invited.