Aird Lab

The Wistar Institute

Philadelphia, PA

Positions open for research technicians!

We are also actively recruiting postdoctoral fellows interested in the intersection between cancer cell metabolism and cell cycle dysregulation.

See “Positions” tab for details.

 

The Aird lab focuses on the reciprocal regulation between cellular metabolism and the cell cycle in cancer.

The interplay between cell cycle and metabolism is bidirectional, although incompletely understood. While proliferating cells require energy and biomass, metabolites can also act as signaling molecules to impact epigenetic and transcriptional programs, thereby influencing biology beyond macromolecule needs. The Aird lab has made fundamental discoveries into how metabolism informs proliferative cell fate decisions by studying two extremes of proliferation: cancer and cellular senescence. Both cancer and senescent cells are highly metabolically active, yet the outcomes of this rewiring are distinct. We aim to ask fundamental questions related to how cell cycle derangement informs metabolic decisions and vice versa. Using cancer as a model system, we aim to answer fundamental questions on the bidirectional control of metabolism and the cell cycle.

Our specific questions:

1)    How do metabolic cues lead to differential cell cycle decisions?

2)    How does cell cycle derangement affect metabolism and what are the consequences of this on intrinsic and extrinsic signaling?

3)    What are the consequences of bidirectional cell cycle and metabolism programs on intrinsic and extrinsic signaling?  

The Aird lab is currently funded by a R37 MERIT, multiple R01s from the NIH/NCI, an Investigator Initiated Research Award from the DoD Ovarian Cancer Research Program, a Partnering PI Award from the DoD Research Program, and internal Wistar Institute funds.

Previous funders include: the American Cancer Society, NCI R00, W. W. Smith Charitable Trust, DoD Ovarian Cancer Research Program, Penn State Cancer Institute, the Sandy Rollman Ovarian Cancer, UPMC Hillman Cancer Center and University of Pittsburgh, Pitt Melanoma SPORE. Prior trainee funders: NCI, NIGMS, Pitt Ovarian SPORE, the HERA Ovarian Cancer Foundation, Melanoma Research Foundation, the Magee Women’s Research Institute, and the Penn State Cancer Institute.

Watch here or read here to learn more about what we do!

Follow Dr. Aird on Twitter @airdlab or Bluesy @airdlab.bsky.social


Lab Members

Lab News


Selected Publications & Preprints

Buj R. Cole AR, Danielson J, Xu J, Hurd D, Kishore A, Kedziora KM, Chen J, Yang B, Barras D, Uboveja A, Amalric A, Saab JA, Wickramasinghe J, Tangudu NK, Levasseur E, Wang H, Minasyan A, Dadey RE, Sharrow AC, Vendetti FP, Rivadeneira DB, Bakkenist CJ, Delgoffe GM, Hempel N, Snyder NW, Bao R, Soloff AC, Kirkwood JM, Laniti DD, Kosenkov AV, Muir A, Das J, Davar D, Mesaros C, and Aird KM. Zinc availability in the tumor microenvironment dictates anti-PD1 response in CDKN2ALow tumors via increased macrophage phagocytosis. bioRxiv. 2025 Feb 08. Doi: 10.1101/2025.02.08.637227

Cole AR, Buj R, Uboveja A, Levasseur E, Wang H, Kedziora KM, Chatoff A, Andress Huacachino A, Marcinkiewicz MM, Amalric A, Yang B, Tangudu NK, Danielson J, Taher Elwah A, White S, Li D, Wallace CT, Lazure F, Elishaev E, Borho L, Jazwinska DE, Laird MS, Atiya H, Bitler BG, Dangaj D,  Coffman LG,  Tseng G, Oesterreich S, Gomes AP, Gurkar AU, Schopfer FJU, Modugno F, Watkins SC, Zervantonakis I, Wayne Stallaert,  Hempel N, Snyder NW, Aird KM. The chemotherapy-induced senescence-associated secretome promotes cell detachment and metastatic dissemination through metabolic reprogramming. bioRxiv. 2025. https://doi.org/10.1101/2023.12.02.569652

Uboveja A, Huang Z, Buj R, Amalric A, Wang H, Tangudu NK, Cole AR, Megill E, Kantner D, Chatoff A, Ahmad H, Marcinkiewicz MM, Disharoon JA, Graff S, Dahl ES, Hempel N, Stallaert W, Sidoli S, Bitler BG, Long DT, Snyder NW, Aird KM. αKG-mediated carnitine synthesis promotes homologous recombination via histone acetylation. bioRxiv. 2024. doi: 10.1101/2024.02.06.578742.

Tangudu NK, Grumet AN, Fang R, Buj R, Cole AR, Uboveja A, Amalric A, Yang B, Huang Z, Happe C, Sun M, Gelhaus SL, MacDonald ML, Hempel N, Snyder NW, Kedziora KM, Valvezan AJ, and Aird KM. ATR promotes mTORC1 activity via de novo cholesterol synthesis. EMBO Rep. 2025 Jul;26(14):3574-3593.

Sharrow AC, Megill Em, Chen AJ, Farooqi A, McGonigal S, Hempel N, Snyder NW, Buckanovich RJ, and Aird KM. Acetate drives ovarian cancer quiescence via ACSS2-mediated acetyl-CoA production. Molecular Metabolism. 2024 Sep 19:102031.

Tangudu NK, Buj R, Wang J, Cole AR, Uboveja A, Fang R, Amalric A, Lyons MA, Chandran UR, Aird KM. De novo purine metabolism is a metabolic vulnerability of cancers with low p16 expression. Cancer Research Communications. 2024 May 2;4(5):1174-1188. PMID: 38626341

Huang Z, Chen CW, Buj R, Tangudu NK, Fang RS, Leon KE, Dahl ES, Varner EL, von Krusenstiern E, Cole AR, Snyder NW, and Aird KM. ATM inhibition drives metabolic adaptation via induction of macropinocytosis. Journal of Cell Biology. 2023 Jan 2;222(1):e202007026.

Leon KE, Buj R, Lesko E, Dahl ES, Chen CW, Imamura Y, Kossenkov AV, Hobbs RP, and Aird KM. DOT1L modulates the senescence-associated secretory phenotype through epigenetic regulation of IL1A. Journal of Cell Biology. 2021 Aug 2;220(8):e202008101.

Leon KE*, Tangudu NK*, Aird KM, and Buj R. Loss of p16: A Bouncer of the Immunological Surveillance? Life. 2021, 11(4), 309.

Buj R, Leon KE, Anguelov MA, and Aird KM. Suppression of p16 alleviates the senescence-associated secretory phenotype. Aging (Albany NY). 2021 Feb 6;13.     

Buj R and Aird KM. p16: Cycling off the Beaten Path. Molecular & Cellular Oncology. 2019;6(6).

Buj R, Chen CW, Dahl ES, Leon KE, Kuskovsky R, Maglakelidze N, Navaratnarajah M, Zhang G, Doan MT, Jiang H, Zaleski M, Kutzler L, Lacko H. Lu Y, Mills GB, Gowda R, Robertson GP, Warrick JI, Herlyn M, Imamura Y, Kimball SR, DeGraff DJ, Snyder NW, and Aird KM. Suppression of p16 increases nucleotide synthesis via mTORC1. Cell Reports. 2019 Aug; 28(8):1971-1980.

Dahl ES, Buj R, Leon KE, Newell JM, Bitler BG, Snyder NW, and Aird KM. Targeting IDH1 as a pro-senescent therapy for high grade serous ovarian cancer. Molecular Cancer Research. 2019 Aug;17(8):1710-1720.