SBME Research Seminar - Dr. Hannah Carter
Immune Checkpoint Blockade (ICB) has revolutionized cancer treatment, however mechanisms determining patient response remain poorly understood. We used machine learning to predict ICB response from germline and somatic biomarkers and studied feature usage by the learned model to uncover putative mechanisms driving superior outcomes. Patients with higher T follicular helper infiltrates were robust to defects in the class-I Major Histocompatibility Complex (MHC-I). Further investigation uncovered different ICB responses in MHC-I versus MHC-II neoantigen reliant tumors across patients. Despite similar response rates, MHC-II reliant responses were associated with significantly longer durable clinical benefit (Discovery: Median OS=63.6 vs. 34.5 months P=0.0074; Validation: Median OS=37.5 vs. 33.1 months, P=0.040). Characteristics of the tumor immune microenvironment reflected MHC neoantigen reliance, and analysis of immune checkpoints revealed LAG3 as a potential target in MHC-II but not MHC-I reliant responses. This study highlights the value of interpretable machine learning models in elucidating the biological basis of therapy responses.
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SBME Seminar: Reconstitution of mammalian life cycle in vitro – Dr. Nobuhiko Hamazaki
April 19, 2024 @ 10:00 am - 11:00 am PDT
SBME Seminar: Reconstitution of mammalian life cycle in vitro – Dr. Nobuhiko Hamazaki
Seminar Abstract:
Mammalian development is still enigmatic processes as it undergoes all the process in mother’s uterus. Historically, simply taking any part of the processes out from the uterus to dish has brought tremendous findings. For example, in vitro fertilization and the subsequent culture of embryos up to the blastocyst stage have given us the opportunity to monitor, manipulate, and investigate post-fertilization development. Here we will introduce two in vitro model systems: directly induced oocyte-like cells (DIOLs) and human advanced gastruloid model, which recapitulates mouse oocyte development and human post-gastrulation development, respectively, entirely in vitro. These systems provide robust and scalable platforms for investigating the mechanisms underlying mammalian life cycles, as well as failures in these processes, including infertility and developmental diseases.
Dr. Nobuhiko Hamazaki’s Biography
I did a 1st Postdoc in Japan in Katsuhiko Hayashi lab and did 2nd Postdoc in Seattle in Jay Shendure lab. Recently I started my own lab at the University of Washington to pursue the fundamental biological questions by integrating genomics tools to stem cell models.
Location:
LSC 1003 (LT3)