91΄σΙρ

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Nikki Lytle, PhD

Nikki K. Lytle, PhD

Assistant Professor

Locations

  • TBRC, C4783

Contact Information

General Interests

Cell state plasticity, tumor evolution, tumor microenvironment, pancreatic cancer, breast cancer

Education

PhD, Biomedical Sciences, University of California San Diego, 2018

Biography

Dr. Lytle completed her graduate work at the University of California San Diego in Dr. Tannishtha Reya’s lab where she focused on identifying signals that are critical for pancreatic cancer initiation, therapy-resistance, and metastasis. Her work contributed to important therapeutically-relevant discoveries including the identification of Musashi as a pancreatic cancer stem cell determinant, and disabling pancreatic cancer progression through blockade of the stem cell regulators ROR-gamma and LIF. She then went on to join Dr. Geoffrey Wahl’s lab at the Salk Institute for her postdoctoral fellowship where she studied how tissue injury can contribute to cell state instability and tumor initiation in breast cancer, or progression to metastasis in pancreatic cancer. Dr. Lytle was named a Hope Funds for Cancer Research Fellow in 2019 for her work in pancreatic cancer. She joined the Department of Surgery at the 91΄σΙρ College of Wisconsin in 2022. Her current research program focuses on cell intrinsic and microenvironmental factors that contribute to pancreatic and breast cancer with the goal of identifying novel therapeutic targets for preventing metastatic progression.

Research Experience

  • Breast Neoplasms
  • Carcinoma, Pancreatic Ductal
  • Cell Plasticity
  • Cell Transformation, Neoplastic
  • Chromatin
  • CRISPR-Cas Systems
  • Disease Models, Animal
  • Epigenesis, Genetic
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Histology

Research Interests

Our understanding of cancer has been challenged in nearly every regard. “Potent” oncogenic mutations are insufficient to drive tumorigenesis from most cells. What factors are required to initiate cancer? Do rare tumor-initiating cells have an inherent “permissive” epigenetic state, or is tumor-initiating potential determined by local signals from the microenvironment? Additionally, tumor cells spread throughout the body early in disease, some with mesenchymal characteristics and others stuck in an epithelial state, suggesting that the route to metastasis may be heterogeneous and complicated. The vast majority of these disseminated cells will die or be cleared by our immune system and only a select few drive metastasis. What properties endow those rare cells to survive and initiate metastases?

My research focuses on understanding cell states that are responsible for tumor initiation, therapy resistance and metastasis. We study human conditions in which cancer progression is either diminished or enhanced as a platform for determining anti- or pro-tumorigenic signals, respectively. We leverage patient samples as the primary source of discovery, and employ multiplexed single cell analyses of tumor and microenvironmental cell populations to identify signals that critically contribute to metastasis or therapy resistance. We utilize elegant mouse models that enable tracking of cell dynamics over time and functional testing of targets, and work to develop new tools to address outstanding questions in cancer biology when current tools are inadequate. Finally, we focus on targets that may be therapeutically actionable with the goal of moving our findings into the clinic to improve patient outcomes.

Publications

  • (Rajbhandari N, Hamilton M, Quintero CM, Ferguson LP, Fox R, Schürch CM, Wang J, Nakamura M, Lytle NK, McDermott M, Diaz E, Pettit H, Kritzik M, Han H, Cridebring D, Wen KW, Tsai S, Goggins MG, Lowy AM, Wechsler-Reya RJ, Von Hoff DD, Newman AM, Reya T.) Cancer Cell. 2023 Nov 13;41(11):1989-2005.e9 PMID: 37802055 PMCID: PMC10836835 10/07/2023

  • (Ferguson LP, Gatchalian J, McDermott ML, Nakamura M, Chambers K, Rajbhandari N, Lytle NK, Rosenthal SB, Hamilton M, Albini S, Wartenberg M, Zlobec I, Galván JA, Karamitopoulou E, Vavinskaya V, Wascher A, Lowy AM, Schürch CM, Puri PL, Bruneau BG, Hargreaves DC, Reya T.) Nat Commun. 2023 Jan 18;14(1):292 PMID: 36653361 PMCID: PMC9849267 01/19/2023

  • (Ma Z, Lytle NK, Chen B, Jyotsana N, Novak SW, Cho CJ, Caplan L, Ben-Levy O, Neininger AC, Burnette DT, Trinh VQ, Tan MCB, Patterson EA, Arrojo E Drigo R, Giraddi RR, Ramos C, Means AL, Matsumoto I, Manor U, Mills JC, Goldenring JR, Lau KS, Wahl GM, DelGiorno KE.) Gastroenterology. 2022 Feb;162(2):604-620.e20 PMID: 34695382 PMCID: PMC8792222 10/26/2021

  • (Gubbala VB, Jytosana N, Trinh VQ, Maurer HC, Naeem RF, Lytle NK, Ma Z, Zhao S, Lin W, Han H, Shi Y, Hunter T, Singh PK, Olive KP, Tan MCB, Kaech SM, Wahl GM, DelGiorno KE.) Gastro Hep Adv. 2022;1(4):682-697 PMID: 36277993 PMCID: PMC9583893 10/25/2022

  • (Ma Z, Lytle NK, Ramos C, Naeem RF, Wahl GM.) Methods Mol Biol. 2022;2471:49-82 PMID: 35175591 PMCID: PMC9663269 02/18/2022

  • (Shi Y, Gao W, Lytle NK, Huang P, Yuan X, Dann AM, Ridinger-Saison M, DelGiorno KE, Antal CE, Liang G, Atkins AR, Erikson G, Sun H, Meisenhelder J, Terenziani E, Woo G, Fang L, Santisakultarm TP, Manor U, Xu R, Becerra CR, Borazanci E, Von Hoff DD, Grandgenett PM, Hollingsworth MA, Leblanc M, Umetsu SE, Collisson EA, Scadeng M, Lowy AM, Donahue TR, Reya T, Downes M, Evans RM, Wahl GM, Pawson T, Tian R, Hunter T.) Nature. 2021 Dec;600(7889):E18 PMID: 34848876 12/02/2021

  • (Spinler K, Bajaj J, Ito T, Zimdahl B, Hamilton M, Ahmadi A, Koechlein CS, Lytle N, Kwon HY, Anower-E-Khuda F, Sun H, Blevins A, Weeks J, Kritzik M, Karlseder J, Ginsberg MH, Park PW, Esko JD, Reya T.) Nat Commun. 2020 Nov 26;11(1):5998 PMID: 33243988 PMCID: PMC7691523 11/28/2020

  • (DelGiorno KE, Chung CY, Vavinskaya V, Maurer HC, Novak SW, Lytle NK, Ma Z, Giraddi RR, Wang D, Fang L, Naeem RF, Andrade LR, Ali WH, Tseng H, Tsui C, Gubbala VB, Ridinger-Saison M, Ohmoto M, Erikson GA, O'Connor C, Shokhirev MN, Hah N, Urade Y, Matsumoto I, Kaech SM, Singh PK, Manor U, Olive KP, Wahl GM.) Gastroenterology. 2020 Nov;159(5):1866-1881.e8 PMID: 32717220 PMCID: PMC7680354 07/28/2020

  • (Li YC, Lytle NK, Gammon ST, Wang L, Hayes TK, Sutton MN, Bast RC Jr, Der CJ, Piwnica-Worms D, McCormick F, Wahl GM.) Proc Natl Acad Sci U S A. 2020 Jun 02;117(22):12121-12130 PMID: 32424096 PMCID: PMC7275768 05/20/2020

  • (Lusardi TA, Lytle NK, Gebril HM, Boison D.) J Caffeine Adenosine Res. 2020 Mar 01;10(1):12-24 PMID: 32181443 PMCID: PMC7071069 03/18/2020

  • (Bersini S, Lytle NK, Schulte R, Huang L, Wahl GM, Hetzer MW.) Life Sci Alliance. 2020 Jan;3(1) PMID: 31959624 PMCID: PMC6971368 01/22/2020

  • (Shi Y, Gao W, Lytle NK, Huang P, Yuan X, Dann AM, Ridinger-Saison M, DelGiorno KE, Antal CE, Liang G, Atkins AR, Erikson G, Sun H, Meisenhelder J, Terenziani E, Woo G, Fang L, Santisakultarm TP, Manor U, Xu R, Becerra CR, Borazanci E, Von Hoff DD, Grandgenett PM, Hollingsworth MA, Leblanc M, Umetsu SE, Collisson EA, Scadeng M, Lowy AM, Donahue TR, Reya T, Downes M, Evans RM, Wahl GM, Pawson T, Tian R, Hunter T.) Nature. 2019 May;569(7754):131-135 PMID: 30996350 PMCID: PMC6565370 04/19/2019