Cytotoxic cells, including natural killer (NK) cells and cytotoxic T cells, recognize and kill infected and transformed cells. Our laboratory investigates mechanisms of recognition of cancer cells and infected cells by natural killer cells and T cells. Furthermore we investigate mechanisms by which tumors and infectious agents naturally activate or inhibit productive responses by cytotoxic cells, or desensitize the cells by inducing anergy. Our aim is to harness these findings to improve existing immunotherapies for cancer and design new ones. We have employed our understanding of NK recognition, activation and inhibition to establish therapy combinations that super-activate NK cells, while at the same time preventing desensitization and inhibition of the cells. These combinations show promise as new therapies for cancers that are refractory to existing immunotherapies.
News and Announcements:
Rutger Luteijn’s paper is now out in Science Signaling. The paper documents the role of the phospholipid PI4P localized to the Golgi in promoting STING signaling. The paper demonstrates the role of ACBD3 in STING signaling, leading to the accumulation of PI4P in the Golgi, and shows that OSBP inhibitors amplify STING signaling by increasing PI4P levels in the Golgi. The paper is a collaboration with the labs of Frank van Kuppeveld and Josh Woodward. March 2024
Yeara Jo was selected as a postdoctoral CIRM Scholar of CIRM Training Program EDUC4-12790, "Training the Next Generation of Biologists and Engineers for Regenerative Medicine." Congradulations to Yeara! Januray 2024
Undergraduates Natalie Liang and Koharu Sakiyama were awarded funding for research in 2023-24 from the Center for Research and Education on Aging (CREA). Congratulations to Kokaru and Natalie! January 2024
Welcome to new postdoctoral fellow, Hannah Ghasemi! October 2023
See our comprehensive review of NK cells in cancer and immunotherapy, in Nature Reviews Immunology: "Roles of natural killer cells in immunity to cancer, and applications to immunotherapy”. February 2023
In a collaborative study with Chris Garcia's lab, we (Yeara Jo) contribute to showing that induced proximity of NK inhibitory recepts with CD45 phosphate is more effective than simple blockade in unleashing NK killing. Inactivating CD94/NKG2A and two Ly49 receptors simultaneously was much more effective than seperately inactivating them. September 2022.
Djem Kissiov’s paper is now out in eLife! Important new findings in NK receptor gene expression mechanisms and random monoallelic gene expression generally. Also has remarkable finding that numerous lineage defining genes (i.e the genes for CD45, Thy-1, CD8a) show a low degree of random monoallelic expression, suggesting that RME may be a universal property of gene expression. May 2022
Natalie Wolf’s paper is now out in PNAS! It shows remarkable synergistic effects of combining STING agonists and an IL-2 superkine in immunotherapy of cancer in numerous mouse models of cancer, including primary sarcomas (with the critical collaboration of Cristina Blaj). This was a “winning combination” for MHC-deficient tumors (where NK cells and CD4 T cells mediated rejection) and MHC I+ tumors (where CD8 T cells and--in the primary tumor model—CD8 cells, CD4 cells and NK cells mediate rejection). This may be an approach to resurrect STING agonist immunotherapy and IL-2 superkine therapy alike. May 2022
Sadly, Natalie Wolf is heading out for the next chapter in her career. It has been a ton of fun to have her in the lab these last years and she accomplished a great deal! Best of luck Natalie! May 2022
Very excited to have two new graduate students joining the lab: Elle Andrews and Abigail Mende! Welcome aboard! May 2022
Wonderful PhD Commencement where Natalie Wolf, Djem Kissiov and Chris Nicolai were officially hooded, Djem and Chris belatedly! May 2022
David was finally able to sign the official book at his pandemic delayed induction into the National Academy of Sciences. April 2022
Raulet Lab had an inspiring scientific retreat at Sea Ranch! March 2022
We are very pleased to welcome MCB rotation student, Elle Andrews, to the lab! March 2022
We are very pleased to welcome MCB rotation student, Charlotte Langner, to the lab! November 2021
Welcome to Alexandros Karampatzakis as a new postdoctoral fellow! October 2021
We are very pleased to welcome MCB rotation student, Abigail Mende, to the lab! September 2021
See the Bilder lab paper on tumor-induced morbidity and opening of the blood brain barrier, featuring mouse tumor data from Natalie Wolf Kim in our lab here, Dev. Cell 2021
Congratulations to postdoc Yeara Jo, who was just awarded the Cancer Research Institute/Irvington Postdoctoral Fellowship molecular mechanisms underlying NK cell anergy and reprogrammability! July 2021
Congratulations to Natalie Wolf, who was awarded a predoctoral fellowship from the Cancer Research Coordinating Committee! June 2021
Delighted to welcome Chenyu Zhang to the lab as a joint graduate student researcher in the DuPage and Raulet labs!
Chris Nicolai's paper published showing NK-Mediated cancer-immunotheraphy induced by STING-agonists! May 2020
Congratulations to postdoc Alan Tubbs, who was just awarded the Cancer Research Institute/Irvington Postdoctoral Fellowship for his research on NK cell regulation in the context of tumor immunology!
Congratulations to Rutger Luteijn whose paper on a transporter for cyclic dinucleotides was accepted at Nature! August, 2019
Congrats Djem Kissiov, who was awarded a predoctoral fellowship from the Cancer Research Coordinating Committee! July 2019
David was elected to the National Academy of Sciences! May, 2019
Michele's paper featured in NIH director's blog!
Michele's paper featured in multiple news columns: here, here, here, here, here, and here!
Assaf's paper and Michele's paper featured on department's website here!
Congratulations to our former colleague, Jim Allison, for his Nobel Prize in Medicine and Physiology— given for his work on cancer immunotherapy at UC Berkeley in the 1990's! We collaborated then to show that CD28 is the constimulatory molecule for T cells. Proof that basic research in animal models transforms human health! See the press release here.
Congrats to Assaf Marcus for having his paper accepted in Immunity!
Raulet Lab, May 2022