Events
Nov
14
CANCELLED - BMG Seminar: Sara Buhrlage, PhDBMG Seminar: Sara Buhrlage, PhD
Chicago - 10:00 AM - 11:00 AM
The Department of Biochemistry and Molecular Genetics Departmental Seminar Series presents: Sara Buhrlage, PhDAssistant Professor, Biological Chemistry and Molecular PharmacologyHarvard Medical SchoolAssistant Professor, Cancer BiologyDana-Farber Cancer Institute
Nov
21
BMG Seminar: The Signaling and Metabolic Landscape Associated with Metastatic Progression - John Blenis, PhD
Chicago - 10:00 AM - 11:00 AM
It is known that primary solid tumors are generally not the cause of cancer-related deaths but that 80-90% of mortality is the result of cancer cells gaining the ability to leave the primary tumor, activate survival processes, invade surrounding tissues, intravasate into the circulation, extravasate into new tissues, and form secondary tumors, often after long latencies. We have discovered that distinct ERK substrate recognition domains make major contributions to specific cancer phenotypes such as proliferation versus metastatic progression. While much is known regarding ERK proliferative signaling mechanisms, much less is understood regarding the role of ERK signaling in the acquisition of metastatic properties. Therefore, defining the signaling mechanisms and biological outcomes downstream of ERK that contribute to the development of metastasis are of critical importance. To discover new processes linked to the initiation and establishment of the metastatic phenotype, we have completed several large-scale screening efforts (gene expression arrays, proteomics, phosphoproteomics, and metabolomics) aimed at mapping the temporal changes that occur during ERK2-driven acquisition of aggressive, mesenchymal phenotypes. These approaches have yielded several new discoveries such as mechanisms of cross-talk between ERK2 and TGFb pathways, chromatin remodeling through regulation of histone chaperones, metabolic reprogramming and identification of metabolites acting as second messengers that drive aging-associated metastasis. How ERK2 and TGFb contribute to chromatin remodeling and metabolic reprogramming will be discussed. John Blenis, PhDAnna Maria and Stephen Kellen Professor of Cancer ResearchProfessor, Department of PharmacologyAssociate Director of Basic Science, Sandra and Edward Meyer Cancer CenterWeill Cornell Medicine
Nov
22
BMG Journal Club
Chicago - 3:30 PM - 5:00 PM
The BMG Journal Club will convene every other Friday from 3:30pm to 5:00pm. This is an opportunity for the department to come together and have in-depth discussions about the current literature and the overall implications of new studies, enhancing everyone’s knowledge of the field at large and about each other’s research interests within the department; providing possible opportunities to collaborate as well. This is also an opportunity to practice vital presentation skills in front of a friendly audience. Pizza and soda will be served.
Dec
05
BMG Seminar: Nrf2 activation promotes lung cancer metastasis by inhibiting the Fbxo22-mediated degradation of Bach1 -Michele Pagano, MD
Chicago - 10:00 AM - 11:00 AM
About 30% of lung adenocarcinomas (LUADs) increase the transcription of antioxidant genes to maintain oxidative homeostasis. This increase is made possible by mutations that stabilize Nrf2, the master transcriptional regulator of the cell’s antioxidant program. These mutations are associated with an aggressive cancer phenotype and either directly target Nfe2L2 (encoding Nrf2) or inactivate Nrf2’s negative regulator, Keap1. Keap1 is a substrate receptor of a CRL3 ubiquitin ligase complex that, in physiological conditions, constitutively targets Nrf2 for degradation. We asked whether LUADs with Keap1 mutations are more aggressive than LUADs harboring wild-type Keap1 due to an increased metastatic burden, and by which mechanism. We found that stabilization of Nrf2 in LUAD activates a pathway that in turn stabilizes Bach1, a transcription factor that controls the expression of a plethora of pro-metastatic genes. Mechanistically, mutations that stabilize Nrf2 drive the Nrf2-mediated induction of heme oxygenase 1 (Ho1), an enzyme responsible for heme catabolism. We also found that heme promotes the interaction of Bach1 with CRL1Fbxo22. Therefore, increased heme catabolism leads to a decrease in free heme, reducing the CRL1Fbxo22-mediated degradation of Bach1. Thus, in normal cells, either Nrf2 is low and Bach1 is high (under unstressed conditions) or Nrf2 is high and Bach1 is low (upon oxidative stress). Instead, LUAD cells paradoxically display high levels of both Nrf2 and Bach1, thus promoting cell survival and inducing cell migration, respectively. We extensively validated our mechanistic results in mouse models of LUAD, as well as in samples of LUAD patients. We propose that: 1) Nrf2 induces lung cancer metastases by reducing heme- and Fbxo22-mediated degradation of Bach1, which in turn activates the transcription of pro-metastatic genes; and 2) drugs targeting the heme pathway represent a promising strategy to block metastasis in LUAD patients. Moreover, we suggest that Ho1 and Bach1 could be used as LUAD biomarkers to improve the design of precision medicine approaches and clinical trials, and to monitor the response to therapy. Michele Pagano, MDChair, Department of Biochemistry and Molecular PharmacologyMay Ellen and Gerald Jay Ritter Professor of Oncology, Department of Biochemistry and Molecular PharmacologyNew York University School of MedicineHoward Hughes Medical Institute Investigator
Jan
17
BMG Journal Club
Chicago - 3:30 PM - 5:00 PM
The BMG Journal Club will convene every other Friday from 3:30pm to 5:00pm. This is an opportunity for the department to come together and have in-depth discussions about the current literature and the overall implications of new studies, enhancing everyone’s knowledge of the field at large and about each other’s research interests within the department; providing possible opportunities to collaborate as well. This is also an opportunity to practice vital presentation skills in front of a friendly audience. Pizza and soda will be served.
Jan
31
BMG Journal Club
Chicago - 3:30 PM - 5:00 PM
The BMG Journal Club will convene every other Friday from 3:30pm to 5:00pm. This is an opportunity for the department to come together and have in-depth discussions about the current literature and the overall implications of new studies, enhancing everyone’s knowledge of the field at large and about each other’s research interests within the department; providing possible opportunities to collaborate as well. This is also an opportunity to practice vital presentation skills in front of a friendly audience. Pizza and soda will be served.
Feb
14
BMG Journal Club
Chicago - 3:30 PM - 5:00 PM
The BMG Journal Club will convene every other Friday from 3:30pm to 5:00pm. This is an opportunity for the department to come together and have in-depth discussions about the current literature and the overall implications of new studies, enhancing everyone’s knowledge of the field at large and about each other’s research interests within the department; providing possible opportunities to collaborate as well. This is also an opportunity to practice vital presentation skills in front of a friendly audience. Pizza and soda will be served.