Department of Cellular & Molecular Physiology
Penn State College of Medicine (Hershey, PA)
Multiple positions open for postdoctoral fellows interested in metabolism.
See “Positions” tab for details.
The Aird lab focuses on:
The mechanisms and pathological implications of cellular senescence. Cellular senescence is a stable cell cycle arrest that is a tumor suppression mechanism and also plays a role in age-related pathologies. In particular, her lab is interested in the intersection between cellular senescence and metabolism. Understanding the mechanisms of how cells undergo and overcome this proliferative arrest may lead to novel therapeutic strategies for both cancer and aging. These projects aim to: 1) understand the earliest events in tumorigenesis; 2) identify novel crosstalk mechanisms between metabolism and epigenetics that underly both the cell cycle arrest and senescence-associated secretory phenotype (SASP); and 3) exploit senescence pathways as novel therapeutic strategies for cancer
Metabolic reprogramming in ovarian cancer. Very little is understood about the metabolic programming of normal Fallopian tube and how these pathways go awry in ovarian cancer. These projects aim to: 1) characterize metabolism in normal Fallopian tube, primary ovarian cancer tumors, tumors within the ascites fluid, and metastatic sites; and 2) use this information to exploit metabolic vulnerabilities as novel ovarian cancer therapies.
Nucleotide metabolism. Homeostasis of nucleotide metabolism is critical for the health of cells. We are interested in understanding novel pathways that regulate nucleotide metabolism and whether nucleotide biosynthesis is a metabolic vulnerability for some cancer cells. These projects aim to understand: 1) the interplay between the cell cycle and nucleotide metabolism; 2) ATR-mTORC1-mediated nucleotide metabolism in cancer cells with low p16; and 3) the cross-talk between nucleotide metabolism and the tumor microenvironment.
The Aird lab is currently funded by an R00 and F31 from the NIH/NCI, a Pilot Award from the Department of Defense Ovarian Cancer Research Program, an award from the Sandy Rollman Ovarian Cancer Foundation, and the Penn State Cancer Institute. Previous funders include the W. W. Smith Charitable Trust.
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shRNA Library Information
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. bioRxiv. https://www.biorxiv.org/content/early/2018/08/17/393876. Accepted at Cell Reports
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. http://mcr.aacrjournals.org/content/early/2019/05/18/1541-7786.MCR-18-1233
Leon KE and Aird KM. Jumonji C Demethylases in Cellular Senescence. https://www.preprints.org/manuscript/201811.0382/v1
Buj R and Aird KM. dNTP Metabolism in Cancer and Metabolic Disease. Front Endocrinol (Lausanne). 2018 Apr 18;9:177. https://www.frontiersin.org/articles/10.3389/fendo.2018.00177/full
Dahl ES and Aird KM. Ataxia-Telangiectasia Mutated Modulation of Carbon Metabolism in Cancer. Frontiers in Oncology. 2017 Nov 29;7:291. https://www.frontiersin.org/articles/10.3389/fonc.2017.00291/full
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, 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.
Bitler BG, Aird KM, Garipov A, Li H, Amatangelo M, Kossenkov AV, Schultz DC, Liu Q, Shih I, Conejo-Garcia JR, Speicher DW, and Zhang R. Targeting EZH2 methyltransferase activity in ARID1A mutated ovarian cancer cells as a synthetic lethal therapeutic strategy. Nature Medicine. 2015 Mar;21(3):231-8.
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.