Research Summary

The Kutys Lab spans disciplinary boundaries between cell biology and engineering to investigate tissue morphogenic processes associated with human development, regeneration and disease. Ultimately, we are interested in uncovering fundamental molecular and mechanical mechanisms that conspire across time and length scales to organize and shape human tissues. To do so, we develop microfluidic, biomimetic human tissue models that recapitulate 3D in vivo architectures, microenvironments, cellular heterogeneity, and morphogenic behaviors that can be examined mechanistically by biochemical and cell biological approaches. Combined with advanced microscopy, cellular and molecular engineering, and 'omic' technologies, our multidisciplinary approach allows us to model, control, and dissect complex multicellular behaviors at a level previously only accessible in vivo. ​Our lab broadly investigates how biochemical and mechanical signals at cell-cell and cell-extracellular matrix adhesions are coordinated across biological scales (molecules to cells to tissues) to maintain normal tissue structure or drive pathology.

Research Funding

  • July 20, 2023 - June 30, 2028 - Decoding cortical Notch signaling and morphogenic instruction at cell-cell interfaces , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R35GM150987
  • December 1, 2023 - October 31, 2025 - 3D biomimetic human tuberculosis granulomas to identify novel host-pathogen interactions , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21AI176234
  • April 15, 2021 - March 31, 2023 - Notch1 and APP signaling in cerebral microvascular dysfunction , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21AG072232
  • February 1, 2020 - January 31, 2023 - Non-canonical Notch1 regulation of proliferation and adherens junctions in breast cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R00CA226366
  • September 1, 2018 - August 31, 2020 - Non-canonical Notch1 regulation of proliferation and adherens junctions in breast cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: K99CA226366

Education

Pennsylvania State University, BS, 2009, Bioengineering
University of North Carolina Chapel Hill, PhD, 2014, Cell and Developmental Biology
Boston University, Postdoctoral Fellow, 2020, Biomedical Engineering

Honors & Awards

  • 2005 - 2009
    Pennsylvania State University Dean's List
  • 2007 - 2008
    Biomaterials and Bionanotechnology Summer Institute (BBSI) Undergraduate Fellowship
  • 2007 - 2009
    Penn State Schreyer Honors Scholar
  • 2009
    Graduation with honors and high distinction in research, Penn State
  • 2010 - 2014
    National Institutes of Health Graduate Partnership Program (GPP) Fellowship
  • 2011 - present
    Faculty of 1000 Associate Faculty Member in Cell Adhesion
  • 2013
    National Institutes of Health Fellows Award for Research Excellence (FARE)
  • 2015 - 2016
    NIH T32 NRSA Fellowship in Translational Research in Regenerative Medicine
  • 2016 - 2018
    The Hartwell Foundation Postdoctoral Fellowship
  • 2018
    Boston University BME Wallace H. Coulter Translational Research Partnership Award
  • 2018 - present
    NIH K99/R00 Pathway to Independence Award (NCI, K99CA226366)

Selected Publications

  1. Dema A, Charafeddine RA, van Haren J, Rahgozar S, Viola G, Jacobs KA, Kutys ML, Wittmann T. Doublecortin reinforces microtubules to promote growth cone advance in soft environments. Curr Biol. 2024 Dec 16; 34(24):5822-5832.e5.  View on PubMed
  2. Chen J, Crouch EE, Zawadzki ME, Jacobs KA, Mayo LN, Choi JJ, Lin PY, Shaikh S, Tsui J, Gonzalez-Granero S, Waller S, Kelekar A, Kang G, Valenzuela EJ, Birrueta JO, Diafos LN, Wedderburn-Pugh K, Di Marco B, Xia W, Han CZ, Coufal NG, Glass CK, Fancy SPJ, Alfonso J, Kriegstein AR, Oldham MC, Garcia-Verdugo JM, Kutys ML, Lehtinen MK, Combes AJ, Huang EJ. Proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage in prenatal human brain. Nat Neurosci. 2024 Nov; 27(11):2115-2129.  View on PubMed
  3. Meyer NP, Singh T, Kutys ML, Nystul TG, Barber DL. Arp2/3 complex activity enables nuclear YAP for naïve pluripotency of human embryonic stem cells. Elife. 2024 Sep 25; 13.  View on PubMed
  4. Viola G, Jacobs KA, Lemière J, Kutys ML, Wittmann T. Quantitative Comparison of Monomeric StayGold Variants Using Protein Nanocages in Living Cells. bioRxiv. 2024 Sep 17.  View on PubMed
  5. Dema A, Charafeddine RA, van Haren J, Rahgozar S, Viola G, Jacobs KA, Kutys ML, Wittmann T. Doublecortin reinforces microtubules to promote growth cone advance in soft environments. bioRxiv. 2024 Feb 29.  View on PubMed
  6. White MJ, Jacobs KA, Singh T, Mayo LN, Lin A, Chen CS, Jun YW, Kutys ML. Notch1 cortical signaling regulates epithelial architecture and cell-cell adhesion. J Cell Biol. 2023 12 04; 222(12).  View on PubMed
  7. Lee E, Chan SL, Lee Y, Polacheck WJ, Kwak S, Wen A, Nguyen DT, Kutys ML, Alimperti S, Kolarzyk AM, Kwak TJ, Eyckmans J, Bielenberg DR, Chen H, Chen CS. A 3D biomimetic model of lymphatics reveals cell-cell junction tightening and lymphedema via a cytokine-induced ROCK2/JAM-A complex. Proc Natl Acad Sci U S A. 2023 10 10; 120(41):e2308941120.  View on PubMed
  8. White MJ, Singh T, Wang E, Smith Q, Kutys ML. 'Chip'-ing away at morphogenesis - application of organ-on-chip technologies to study tissue morphogenesis. J Cell Sci. 2023 10 01; 136(19).  View on PubMed
  9. Stashko C, Hayward MK, Northey JJ, Pearson N, Ironside AJ, Lakins JN, Oria R, Goyette MA, Mayo L, Russnes HG, Hwang ES, Kutys ML, Polyak K, Weaver VM. A convolutional neural network STIFMap reveals associations between stromal stiffness and EMT in breast cancer. Nat Commun. 2023 06 15; 14(1):3561.  View on PubMed
  10. Adler FR, Anderson ARA, Bhushan A, Bogdan P, Bravo-Cordero JJ, Brock A, Chen Y, Cukierman E, DelGiorno KE, Denis GV, Ferrall-Fairbanks MC, Gartner ZJ, Germain RN, Gordon DM, Hunter G, Jolly MK, Karacosta LG, Mythreye K, Katira P, Kulkarni RP, Kutys ML, Lander AD, Laughney AM, Levine H, Lou E, Lowenstein PR, Masters KS, Pe'er D, Peyton SR, Platt MO, Purvis JE, Quon G, Richer JK, Riddle NC, Rodriguez A, Snyder JC, Lee Szeto G, Tomlin CJ, Yanai I, Zervantonakis IK, Dueck H. Modeling collective cell behavior in cancer: Perspectives from an interdisciplinary conversation. Cell Syst. 2023 04 19; 14(4):252-257.  View on PubMed
  11. Aw WY, Cho C, Wang H, Cooper AH, Doherty EL, Rocco D, Huang SA, Kubik S, Whitworth CP, Armstrong R, Hickey AJ, Griffith B, Kutys ML, Blatt J, Polacheck WJ. Microphysiological model of PIK3CA-driven vascular malformations reveals a role of dysregulated Rac1 and mTORC1/2 in lesion formation. Sci Adv. 2023 02 15; 9(7):eade8939.  View on PubMed
  12. White MJ, Jacobs KA, Singh T, Kutys ML. Notch1 cortical signaling regulates epithelial architecture and cell-cell adhesion. bioRxiv. 2023 Jan 23.  View on PubMed
  13. Kwak M, Southard KM, Kim WR, Lin A, Kim NH, Gopalappa R, Lee HJ, An M, Choi SH, Jung Y, Noh K, Farlow J, Georgakopoulos A, Robakis NK, Kang MK, Kutys ML, Seo D, Kim HH, Kim YH, Cheon J, Gartner ZJ, Jun YW. Adherens junctions organize size-selective proteolytic hotspots critical for Notch signalling. Nat Cell Biol. 2022 12; 24(12):1739-1753.  View on PubMed
  14. Mayo LN, Kutys ML. Conversation before crossing: dissecting metastatic tumor-vascular interactions in microphysiological systems. Am J Physiol Cell Physiol. 2022 11 01; 323(5):C1333-C1344.  View on PubMed
  15. Doyle AD, Sykora DJ, Pacheco GG, Kutys ML, Yamada KM. 3D mesenchymal cell migration is driven by anterior cellular contraction that generates an extracellular matrix prestrain. Dev Cell. 2021 03 22; 56(6):826-841.e4.  View on PubMed
  16. Kutys ML, Polacheck WJ, Welch MK, Gagnon KA, Koorman T, Kim S, Li L, McClatchey AI, Chen CS. Uncovering mutation-specific morphogenic phenotypes and paracrine-mediated vessel dysfunction in a biomimetic vascularized mammary duct platform. Nat Commun. 2020 07 06; 11(1):3377.  View on PubMed
  17. Polacheck WJ, Kutys ML, Tefft JB, Chen CS. Microfabricated blood vessels for modeling the vascular transport barrier. Nat Protoc. 2019 05; 14(5):1425-1454.  View on PubMed
  18. Wang WY, Pearson AT, Kutys ML, Choi CK, Wozniak MA, Baker BM, Chen CS. Extracellular matrix alignment dictates the organization of focal adhesions and directs uniaxial cell migration. APL Bioeng. 2018 Dec; 2(4):046107.  View on PubMed
  19. Chopra A, Kutys ML, Zhang K, Polacheck WJ, Sheng CC, Luu RJ, Eyckmans J, Hinson JT, Seidman JG, Seidman CE, Chen CS. Force Generation via β-Cardiac Myosin, Titin, and α-Actinin Drives Cardiac Sarcomere Assembly from Cell-Matrix Adhesions. Dev Cell. 2018 01 08; 44(1):87-96.e5.  View on PubMed
  20. Polacheck WJ, Kutys ML, Yang J, Eyckmans J, Wu Y, Vasavada H, Hirschi KK, Chen CS. A non-canonical Notch complex regulates adherens junctions and vascular barrier function. Nature. 2017 12 14; 552(7684):258-262.  View on PubMed

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