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: In Vitro Gametogenesis: Advancing Understanding and Application – Dr. Katsuhiko Hayashi
April 19, 2024 @ 11:00 am - 12:00 pm PDT
SBME Seminar: In Vitro Gametogenesis: Advancing Understanding and Application – Dr. Katsuhiko Hayashi
Seminar Abstract:
The reconstitution of gametogenesis using pluripotent stem cells, which eventually produces functional gametes, has long been sought in reproductive biology and developmental biology, as it would contribute not only to a better understanding of the mechanisms underlying totipotency but also to an alternative source of gametes for reproduction. So far, we have developed culture systems that induce primordial germ cells, oocytes, and female gonadal somatic cells from mouse pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). By using these systems, it becomes possible to produce functional eggs from ESCs/iPSCs entirely in culture without the need for embryonic cells. These culture systems are extremely useful, as genetic function in not only germ cells but also surrounding somatic cells can be easily and swiftly evaluated in culture. In the seminar, I will update recent advances in the reconstitution of gametogenesis and new findings in the mechanisms underlying germ cell development.
Dr. Katsuhiko Hayashi’s Biography
Katsuhiko Hayashi (born Dec. 2, 1971), a full professor in Department of Genome Biology, Graduate School of Medicine, Osaka University, is working on germ cell development and its reconstitution in vitro through his career: 1994-1996, MS course of Meiji University; 1996-2002, an assistant professor in Tokyo University of Science; 2002-2005, a staff researcher in Osaka Medical Center (Ph.D. 2004); 2005-2009, post-doctoral fellow in the Gurdon Institute, University of Cambridge; 2009-2014, associate professor in Kyoto University; and 2014-2021 a full professor in Kyushu University. From 2021, He has been in the current position in Osaka University. The research aim of the Hayashi’s group is to understand genetic and epigenetic regulation of mammalian oocyte differentiation using a unique culture system that produces oocytes from pluripotent stem cells.
Location:
LSC 1003 (LT3)