Harvard Medical School
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Publication American Jewish Physicians and a Biological basis for Jewishness from the 19th to the 21st Century
(2025-02-20) Satin, David; Alon, LeighPublication SKI complex loss renders 9p21.3-deleted or MSI-H cancers dependent on PELO
(Springer Science and Business Media LLC, 2025-02-05) Borck, Patricia C.; Boyle, Isabella; Jankovic, Kristina; Bick, Nolan; Foster, Kyla; Lau, Anthony C.; Parker-Burns, Lucy I.; Lubicki, Daniel A.; Li, Tianxia; Borah, Ashir A.; Lofaso, Nicholas J.; Das Sharma, Sohani; Chan, Tessla; Kishen, Riya V.; Adeagbo, Anisah; Raghavan, Srivatsan; Aquilanti, Elisa; Prensner, John R.; Krill-Burger, J. Michael; Golub, Todd R.; Campbell, Catarina D.; Dempster, Joshua M.; Chan, Edmond M.; Vazquez, FranciscaCancer genome alterations often lead to vulnerabilities that can be used to selectively target cancer cells. Various inhibitors of such synthetic lethal targets are FDA-approved or in clinical trials, highlighting the potential of this approach.1–3 Here, we analyzed large-scale CRISPR knockout screening data and identified a new synthetic lethal target, pelota mRNA surveillance and ribosome rescue factor (PELO), for two independent molecular subtypes of cancer: biallelic deletion of chromosomal region 9p21.3 (9p21.3-/-) or microsatellite instability-high (MSI-H). In 9p21.3-/- cancers, PELO dependency emerges from biallelic deletion of the 9p21.3 gene focadhesin (FOCAD), a stabilizer of the superkiller complex (SKIc). In MSI-H cancers, PELO is required due to MSI-H-associated mutations in tetratricopeptide repeat domain 37 (TTC37), a critical component of the SKIc. We show that both cancer subtypes converge to destabilize the SKIc, which extracts mRNA from stalled ribosomes. In SKIc-deficient cells, PELO depletion induces the unfolded protein response (UPR), a stress response to accumulated misfolded or unfolded nascent polypeptides. Together, our findings nominate PELO as a promising therapeutic target for a large patient population with cancers characterized as MSI-H with deleterious TTC37 mutations or with biallelic 9p21.3 deletions involving FOCAD.
Publication Efferocytosis drives a tryptophan metabolism pathway in macrophages to promote tissue resolution
(Springer Science and Business Media LLC, 2024-09-06) Sukka, Santosh R.; Ampomah, Patrick B.; Darville, Lancia N. F.; Ngai, David; Wang, Xiaobo; Kuriakose, George; Xiao, Yuling; Shi, Jinjun; Koomen, John M.; McCusker, Robert H.; Tabas, IraPublication The Historical Recognition of Pain Sensitization: The Development of Understanding Gynecological Pain
(2025-01-16) Jarrell, John; Satin, DavidPublication Inherently Limited by our Imaginations: Health Anxieties, Politics, and the History of the Climate Crisis
(2024-09-19) Jones, David; Satin, DavidPublication Jewish Medicine and Jewish Physicians In The Ghetto
(2021-05-12) Offer, Miriam; Satin, DavidPublication Society, Patients, and Nazi Psychiatry: A History of Reappraisal
(2021-11-18) Münch, Lea; Satin, DavidPublication Jewish Prisoner-Physicians During the Holocaust: Macro and Micro Contexts
(2021-04-14) Siegel, Sari J.; Satin, DavidPublication Medicine During The Nazi Period and the Holocaust: Myths, Historical Evidence and Implications for Medical Ethics and Professionalism
(2021-02-10) Roelcke, Volker; Satin, DavidPublication The First Delinquency Prevention Experiment: Origins and Impact of the Cambridge-Somerville Youth Study
(2023-12-21) Zane, Steven; Satin, David