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.

At the molecular level, we are experts in elucidating new mechanisms underlying adhesion biology, the interactions of cells with their neighbors and their microenvironment. We study how core adhesion molecules like cadherins and integrins integrate and orchestrate chemical and mechano-signaling to specify multicellular behavior, proper organization and differentiation of complex tissues, as well as facilitate the progression of disease.

At the cellular level, we develop and apply quantitative imaging and molecular tools (optogenetics, synthetic biology, microenvironment biomaterials/patterning) that allow us to measure, direct, and perturb cellular behaviors to understand how collective decisions initiate and propagate within tissues.

At the tissue level, we engineer organotypic 3D microfluidic models of human tissues with defined architectures and microenvironments in vitro that permit the simulation, molecular dissection, and quantitative analysis of in vivo-like morphogenic processes. We are working to combine these platforms with organoid systems, unbiased proteomics, and single-cell analyses to build spatio-temporal road maps of human development and disease.

Research Funding

  • 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. 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 Jun 15; 14(1):3561.  View on PubMed
  2. 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
  3. 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
  4. 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
  5. 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 Dec; 24(12):1739-1753.  View on PubMed
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. Kutys ML, Chen CS. Forces and mechanotransduction in 3D vascular biology. Curr Opin Cell Biol. 2016 10; 42:73-79.  View on PubMed
  14. Kutys ML, Yamada KM. Rho GEFs and GAPs: emerging integrators of extracellular matrix signaling. Small GTPases. 2015; 6(1):16-9.  View on PubMed
  15. Kutys ML, Yamada KM. An extracellular-matrix-specific GEF-GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration. Nat Cell Biol. 2014 Sep; 16(9):909-17.  View on PubMed
  16. Doyle AD, Petrie RJ, Kutys ML, Yamada KM. Dimensions in cell migration. Curr Opin Cell Biol. 2013 Oct; 25(5):642-9.  View on PubMed
  17. Kutys ML, Doyle AD, Yamada KM. Regulation of cell adhesion and migration by cell-derived matrices. Exp Cell Res. 2013 Oct 01; 319(16):2434-9.  View on PubMed
  18. Li X, Zhou Q, Sunkara M, Kutys ML, Wu Z, Rychahou P, Morris AJ, Zhu H, Evers BM, Huang C. Ubiquitylation of phosphatidylinositol 4-phosphate 5-kinase type I γ by HECTD1 regulates focal adhesion dynamics and cell migration. J Cell Sci. 2013 Jun 15; 126(Pt 12):2617-28.  View on PubMed
  19. Doyle AD, Kutys ML, Conti MA, Matsumoto K, Adelstein RS, Yamada KM. Micro-environmental control of cell migration--myosin IIA is required for efficient migration in fibrillar environments through control of cell adhesion dynamics. J Cell Sci. 2012 May 01; 125(Pt 9):2244-56.  View on PubMed
  20. Kutys ML, Fricks J, Hancock WO. Monte Carlo analysis of neck linker extension in kinesin molecular motors. PLoS Comput Biol. 2010 Nov 04; 6(11):e1000980.  View on PubMed

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