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, and Investigator Initiated Research Award from the DoD Ovarian Cancer Research Program, and multiple internal funds. Trainees in the lab are funded by the Ovarian Cancer SPORE (Buj), NIH T32 (Cole), DoD (Tangudu), the Ovarian Cancer Research Alliance (Uboveja), and the HERA Foundation (Uboveja).

Previous funders include: the American Cancer Society, W. W. Smith Charitable Trust, DoD Ovarian Cancer Research Program, Penn State Cancer Institute, the Sandy Rollman Ovarian Cancer. Prior trainee funders: the HERA Foundation (Tangudu), Melanoma Research Foundation (Buj), Foundation, NCI [R00 and F31 (Dahl and Leon)], and a Penn State Cancer Institute Postdoctoral Fellowship (Buj).

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

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

Selected Publications & Preprints

Tangudu NK, Buj R, Wang H, Wang J, Cole AR, Uboveja A, Fang R, Amalric A, Sajjakulnukit P, Lyons MA, Cooper K, Hempel N, Snyder NW, Lyssiotis CA, Chandran UR, and Aird KM. De novo purine metabolism is a metabolic vulnerability of cancers with low p16 expression. bioRxiv. 2023 July; :2023.07.15.549149. doi: 10.1101/2023.07.15.549149.

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.

Chen CW, Buj R, Dahl ES, Leon KE, and Aird KM. ATM inhibition synergizes with fenofibrate in high grade serous ovarian cancer cells. Heliyon. Sept 2020.            

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.

Leon KE and Aird KM. Jumonji C Demethylases in Cellular Senescence. Genes (Basel). 2019 Jan 9;10(1). pii: E33.

Buj R and Aird KM. dNTP Metabolism in Cancer and Metabolic Disease. Front Endocrinol (Lausanne). 2018 Apr 18;9:177.

Dahl ES and Aird KM. Ataxia-Telangiectasia Mutated Modulation of Carbon Metabolism in Cancer. Frontiers in Oncology. 2017 Nov 29;7:291.

Karakashev S, Aird KM. Ovarian cancer: how can resistance to chemotherapy be tackled? Future Oncol. 2017 Dec;13(30):2737-2739.

Aird KM, Iwasaki O, Kossenkov AV, Tanizawa H, Fatkhutdinov, Bitler BG, Le L, Alicea G, Yang T, Johnson FB, Noma K, and Zhang R. HMGB2 orchestrates the chromatin landscape of senescence-associated secretory phenotype gene loci.  Journal of Cell Biology. 2016 Nov 7;215(3):325-334.

Fatkhudinov N, Sproesser K, Krepler C, Liu Q, Brafford PA, Herlyn M, Aird KM, and Zhang R. Targeting ribonucleotide reductase M2 and mutant BRAF is a novel combinatorial strategy for melanoma.  Mol Cancer Res. 2016 Sep;14(9):767-75.

Aird KM, Zhang R. ATM in Senescence. Oncotarget. 2015 Jun 20;6(17):14729-30.

Aird KM, Worth AJ, Snyder NW, Lee JV, Sivanand S, Blair IA, Wellen KE, and Zhang R. ATM couples replication stress and metabolism reprogramming during cellular senescence. Cell Reports. 2015 May;11(6):893-901.

Aird KM and Zhang R. Metabolic alterations accompanying oncogene-induced senescence. Molecular & Cellular Oncology, 2014;1(3).

Aird KM and Zhang R. Nucleotide Metabolism, Oncogene-Induced Senescence and Cancer. Cancer Letters. 2014 Jan 28;356(2 Pt A):204-10.

Aird KM, Li H, Xin F, Konstantinopoulos PA, and Zhang R. Identification of ribonucleotide reductase M2 as a potential target for pro-senescence therapy in epithelial ovarian cancer. Cell Cycle. 2013 Oct 29;13(2).

Aird KM, Zhang G, Li H, Tu Z, Bitler BG, Garipov A, Wu H, Wei Z, Wagner SN, Herlyn M, and Zhang R. Suppression of nucleotide metabolism underlies the establishment and maintenance of oncogene-induced senescence. Cell Reports. 2013 Apr 25;3(4):1252-65.