Recent News - Kaelin Lab

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2026

Publications:

Abu-Remaileh M, Stransky LA, Bhalerao N, Shirole NH, Jiang Q, Saad E, Machaalani M, Vigeant SM, Woldemichael H, Xu C, Lu J, Wei H, Liu Z, Sun W, Enomoto K, Choueiri TK, Pitarresi JR, Carr SA, Udeshi ND, Kaelin WG Jr. Targeting of HIF2-driven cachexia in kidney cancer. Nat Med. 2026 Jan;32(1):245-257. doi: 10.1038/s41591-025-04054-2. Epub 2025 Nov 28. PMID: 41315757
Abu-Remaileh M, Stransky LA, Bhalerao N, Shirole NH, Jiang Q, Saad E, Machaalani M, Vigeant SM, Woldemichael H, Xu C, Lu J, Wei H, Liu Z, Sun W, Enomoto K, Choueiri TK, Pitarresi JR, Carr SA, Udeshi ND, Kaelin WG Jr. Publisher Correction: Targeting of HIF2-driven cachexia in kidney cancer. Nat Med. 2026 Feb;32(2):766. doi: 10.1038/s41591-026-04236-6. PMID: 41606123
Tsai AC, Lin MD, Puliyappadamba VT, Junginger DM, Donovan VG, Kaplan EG, Drepanos LM, Wakimoto H, Cahill DP, Losman JA, Mouw KW, Abdullah KG, Doench JG, Nash D, Vitt D, Gege C, Kohlhof H, McBrayer SK, Kaelin WG, Shi DD. KDM6 Enzymes are the Mechanistic Targets of Mutant IDH that Dictate Replication Stress Sensitivity. bioRxiv [Preprint]. 2026 Apr 17:2026.04.14.715350. doi: 10.64898/2026.04.14.715350. PMID: 42039522

Announcements:

Diana Shi, MD has recently started her own laboratory as an independent investigator at the Krantz Family Center for Cancer Research at the Mass General Brigham Cancer Institute. The Shi Laboratory aims to understand how IDH mutations induce metabolic, epigenetic, and transcriptional changes in glioma in order to develop new treatments for this disease.
William Kaelin, MD was awarded a Yosemite-American Cancer Society Grant to study The Endogenous Retroviruses as Emerging Targets for Cancer Vaccines
William Kaelin, MD received the Distinguished Medical Alumnus Award from the Johns Hopkins University School of Medicine.
William Kaelin MD received the Distinguished Alumni Award from Duke University School of Medicine
Diana Shi MD was the recipient of an ASCI / Young Physician-Scientist Award
Matthew Boudreau, PhD will be leaving the lab in mid-September to embark on an exciting journey as Senior Principal Scientist, Scientific Co-Founder, and Chemical Biology Lead at a new start-up.

2025

Publications:

Jiang Q, Braun DA, Clauser KR, Ramesh V, Shirole NH, Duke-Cohan JE, Nabilsi N, Kramer NJ, Forman C, Lippincott IE, Klaeger S, Phulphagar KM, Chea V, Kim N, Vanasse AP, Saad E, Parsons T, Carr-Reynolds M, Carulli I, Pinjusic K, Jiang Y, Li R, Syamala S, Rachimi S, Verzani EK, Stevens JD, Lane WJ, Camp SY, Meli K, Pappalardi MB, Herbert ZT, Qiu X, Cejas P, Long HW, Shukla SA, Van Allen EM, Choueiri TK, Churchman LS, Abelin JG, Gurer C, MacBeath G, Childs RW, Carr SA, Keskin DB, Wu CJ, Kaelin WG Jr. HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy. Cell. 2025 Feb 25:S0092-8674(25)00156-4. doi: 10.1016/j.cell.2025.01.046. Online ahead of print. PMID: 40023154
Shirole NH, Kesar D, Lee Y, Goodale A, Syamala S, Kukreja S, Li R, Qiu X, Yu W, Goldman S, Cejas P, Long HW, Adelman K, Doench JG, Sellers WR, Kaelin WG. Requirement for Cyclin D1 Underlies Cell Autonomous HIF2-Dependence in Kidney Cancer. Cancer Discov. 2025 Apr 4. doi: 10.1158/2159-8290.CD-24-1378. Online ahead of print.
Boudreau MW, Freire VF, Corbett SC, Martínez-Fructuoso L, Kumar R, Thornburg CC, Akee RK, Peyser BD, Jiang Q, Splaine J, Pfaff JL, Chandler BC, Abeja DM, Donovan KA, Che J, Lampson BL, Szajner P, Smith JA, Koduri V, Grkovic T, O'Keefe BR, Kaelin WG Jr. Positive Selection Screen for Natural Product b-Catenin Inactivators. bioRxiv [Preprint]. 2025 Aug 27:2025.08.27.671140. doi: 10.1101/2025.08.27.671140. PMID: 40909631. Preprint.
Abu-Remaileh M, Stransky LA, Bhalerao N, Shirole NH, Jiang Q, Saad E, Machaalani M, Vigeant SM, Woldemichael H, Xu C, Lu J, Wei H, Liu Z, Sun W, Enomoto K, Choueiri TK, Pitarresi JR, Carr SA, Udeshi ND, Kaelin WG Jr. HIF2-driven PTHrP Causes Cachexia and Hypercalcemia in Kidney Cancer: Treatment with HIF2 Inhibitors. bioRxiv [Preprint]. 2025 Sep 11:2025.09.09.675147. doi: 10.1101/2025.09.09.675147. PMID: 40964365.
Kaelin WG Jr. Killing the Science Golden Goose. Am J Med. 2025 Sep;138(9):1181 1182. doi: 10.1016/j.amjmed.2025.04.003. Epub 2025 Apr 15. PMID: 40246005.
Kaelin WG Jr. Making sense of low-complexity domains: The 2025 Lasker Basic Science Award. Proc Natl Acad Sci U S A. 2025 Sep 16;122(37):e2519778122. doi: 10.1073/pnas.2519778122. Epub 2025 Sep 11. PMID: 40932260.

2024

Publications:

Lampson BL, Ramίrez AS, Baro M, He L, Hegde M, Koduri V, Pfaff JL, Hanna RE, Kowal J, Shirole NH, He Y, Doench JG, Contessa JN, Locher KP, Kaelin WG Jr. Positive selection CRISPR screens reveal a druggable pocket in an oligosaccharyltransferase required for inflammatory signaling to NF-κB. Cell. 2024 Apr 25;187(9):2209-2223.e16. doi: 10.1016/j.cell.2024.03.022. PMID: 38670073
Wyant GA, Jiang Q, Singh M, Qayyum S, Levrero C, Maron BA, Kaelin WG Jr. Induction of DEPP1 by HIF Mediates Multiple Hallmarks of Ischemic Cardiomyopathy. Circulation. 2024 Jun 17. doi: 10.1161/CIRCULATIONAHA.123.066628. Online ahead of print. PMID: 38881449
Abu-Remaileh M, Persky NS, Lee Y, Root DE, Kaelin WG Jr. Total loss of VHL gene function impairs neuroendocrine cancer cell fitness due to excessive HIF2α activity. Proc Natl Acad Sci U S A. 2024 Oct;121(40):e2410356121. doi: 10.1073/pnas.2410356121. Epub 2024 Sep 25. PMID: 39320914 Free PMC article
Stransky LA, Gao W, Schmidt LS, Bi K, Ricketts CJ, Ramesh V, James A, Difilippantonio S, Ileva L, Kalen JD, Karim B, Jeon A, Morgan T, Warner AC, Turan S, Unite J, Tran B, Choudhari S, Zhao Y, Linn DE, Yun C, Dhandapani S, Parab V, Pinheiro EM, Morris N, He L, Vigeant SM, Pignon JC, Sticco-Ivins M, Signoretti S, Van Allen EM, Linehan WM, Kaelin WG Jr. Toward a CRISPR-based mouse model of Vhl-deficient clear cell kidney cancer: Initial experience and lessons learned. Proc Natl Acad Sci U S A. 2024 Oct 8;121(41):e2408549121. doi: 10.1073/pnas.2408549121. Epub 2024 Oct 4. PMID: 39365820

Announcements:

Tamar Berger, MD, PhD was selected as a Lubin Family Foundaton Scholar.

2023

Publications:

Shi DD, Lee JH, Wang AC, Khanal J, Gao W, Kaelin WG Jr, McBrayer SK. Protocol to establish a genetically engineered mouse model of IDH1-mutant astrocytoma. STAR Protoc. 2023 May 6;4(2):102281. doi: 10.1016/j.xpro.2023.102281. Online ahead of print. PMID: 37149859 Free PMC article PubMed Central PMCID: PMC10189469.

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Shirole NH, Kaelin WG Jr. von-Hippel Lindau and Hypoxia-Inducible Factor at the Center of Renal Cell Carcinoma Biology. Hematol Oncol Clin North Am. 2023 Oct;37(5):809-825. doi: 10.1016/j.hoc.2023.04.011. Epub 2023 Jun 1. PMID: 37270382 Review.
Shi DD, Kaelin WG. The INDIGO trial: Precision medicine finally comes to glioma. Neuro Oncol. 2023 Nov 2;25(11):1918-1919. doi: 10.1093/neuonc/noad162. PMID: 37698505 No abstract available.

Announcements:

Adam Kibel, MD has been appointed the inaugural incumbent of the DiNovi Distinguished Chair in Urology at Brigham and Women's Hospital.
Nitin Shirole, PhD received a Career Enhancement Program Award - (Funded by Dana-Farber/Harvard Cancer Center Kidney Cancer Spore)

2022

Publications:

Stransky LA, Vigeant SM, Huang B, West D, Denize T, Walton E, Signoretti S, Kaelin WG Jr. Sensitivity of VHL mutant kidney cancers to HIF2 inhibitors does not require an intact p53 pathway. Proc Natl Acad Sci U S A. 2022 Apr 5;119(14):e2120403119. doi: 10.1073/pnas.2120403119. Epub 2022 Mar 31. PMID: 35357972 PMCID: PMC9168943
Wyant GA, Yu W, Doulamis IP, Nomoto RS, Saeed MY, Duignan T, McCully JD, Kaelin WG Jr. Mitochondrial remodeling and ischemic protection by G protein-coupled receptor 35 agonists. Science. 2022 Aug 5;377(6606):621-629. doi: 10.1126/science.abm1638. Epub 2022 Aug 4. PMID: 35926043 PMCID: PMC9639781
Shi DD, Savani MR, Levitt MM, Wang AC, Endress JE, Bird CE, Buehler J, Stopka SA, Regan MS, Lin YF, Puliyappadamba VT, Gao W, Khanal J, Evans L, Lee JH, Guo L, Xiao Y, Xu M, Huang B, Jennings RB, Bonal DM, Martin-Sandoval MS, Dang T, Gattie LC, Cameron AB, Lee S, Asara JM, Kornblum HI, Mak TW, Looper R, Nguyen QD, Signoretti S, Gradl S, Sutter A, Jeffers M, Janzer A, Lehrman MA, Zacharias LG, Mathews TP, Losman JA, Richardson TE, Cahill DP, DeBerardinis RJ, Ligon KL, Xu L, Ly P, Agar NYR, Abdullah KG, Harris IS, Kaelin WG Jr, McBrayer SK. De novo pyrimidine synthesis is a targetable vulnerability in IDH mutant glioma. Cancer Cell. 2022 Aug 12:S1535-6108(22)00324-5. Doi 10.1016/j.ccell.2022.07.011. Online ahead of print. PMID: 35985343 PMCID: PMC9515386
Kaelin WG Jr. The Jeremiah Metzger Lecture: Von Hippel-Lindau Disease: Insights into Oxygen Sensing, Cancer and Drugging the Undruggable. Trans of the Am Clin and Climatological Assoc 2022;132:170-181. 114.
Kaelin WG Jr. Von Hippel-Lindau disease: insights into oxygen sensing, protein degradation, and cancer. J Clin Invest. 2022 Sep 15;132(18):e162480. doi: 10.1172/JCI162480. PMID: 36106637

Announcements:

Diana Shi, MD was among the inaugural recipients of a Lubin Family Foundation Scholar Award.
Qinqin Jiang, PhD received a Kidney Cancer Research Program Postdoctoral Fellowship Award from DoD.
Nitin Shirole, PhD received a Hope Funds Sakonnet Fellowship - (Funded by Hope Funds for Cancer Research)