Kevin A. Janes

Professor, Biomedical Engineering

Primary Location

PO Box 800759

Website

Bio & Overview

Changes in cellular behavior underlie development, disease, and homeostasis. The response of cells to external factors depends upon the synthesis, degradation, and modification of genes and proteins. These regulated events act as "signals" for coordinating cell function. Intracellular signaling is highly dynamic, interconnected, and context dependent, making it difficult to predict how any one signal contributes to the control of cell fate. Understanding how signaling networks enable cells to respond to their environment is important for diseases such as cancer, where the molecular "signal processing" has gone awry and cellular responses are inappropriate. Our group develops experimental and computational techniques for quantitatively monitoring signaling networks as they become activated by diverse stimuli and perturbations. These tools allow us to collect complex datasets, which can be analyzed by "data-driven" modeling to address network-level questions about signal transduction. Fundamentally, our approach is problem driven, involving techniques that range from enzyme-activity assays in cell populations to gene-expression measurements in individual microdissected cells. We are currently interested in studying the tissue responses of colonic epithelia and the morphogenetic responses of 3D-cultured mammary epithelia in vitro.

Academic Information

Department: Biomedical Engineering

Academic Title: Professor

Primary Education

BS, Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 1999
PhD, Bioengineering, Massachusetts Institute of Technology, Cambridge, MA, 2005
Postdoc, Cell Biology, Harvard Medical School, Boston, MA, 2008

Other Appointments

Professor, Biochemistry and Molecular Genetics
Biochemistry and Molecular Genetics
Pharmacology

Other Affiliations

Member, Women's Oncology Program
Cardiovascular Research Center
MSTP
BIMS

Research Interests

Systems-biology approaches to cancer biology and virology.

Research Disciplines

Biochemistry
Bioinformatics and Genomics
Biotechnology
Cancer Biology
Cardiovascular Biology
Computational Biology
Experimental Pathology
Infectious Diseases/Biodefense
Microbiology
Molecular Biology

Research Opportunities

Cancer Biology
Computational Biology
Microbiology

PhD Programs

Biochemistry & Molecular Genetics
Biomedical Engineering
Experimental Pathology

Selected Publications

2024

Griffiths, C. D., Shah, M., Shao, W., Borgman, C. A., & Janes, K. A. (2024). Three Modes of Viral Adaption by the Heart.. bioRxiv. doi:10.1101/2024.03.28.587274

Przanowska, R. K., Labban, N., Przanowski, P., Hawes, R. B., Atkins, K. A., Showalter, S. L., & Janes, K. A. (2024). Patient-derived response estimates from zero-passage organoids of luminal breast cancer.. bioRxiv. doi:10.1101/2024.03.24.586432

Paudel, B. B., Tan, S. -F., Fox, T. E., Ung, J., Golla, U., Shaw, J. J. P., . . . Loughran, T. P. (2024). Acute myeloid leukemia stratifies as 2 clinically relevantsphingolipidomic subtypes. BLOOD ADVANCES, 8(5), 1137-1142. doi:10.1182/bloodadvances.2023010535

2023

Sweatt, A. J., Griffiths, C. D., Paudel, B. B., & Janes, K. A. (2023). Proteome-wide copy-number estimation from transcriptomics.. bioRxiv. doi:10.1101/2023.07.10.548432

Wang, L., Paudel, B. B., McKnight, R. A., & Janes, K. A. (2023). Nucleocytoplasmic transport of active HER2 causes fractional escape from the DCIS-like state. NATURE COMMUNICATIONS, 14(1). doi:10.1038/s41467-023-37914-x

2022

Przanowska, R. K., Weidmann, C. A., Saha, S., Cichewicz, M. A., Jensen, K. N., Przanowski, P., . . . Dutta, A. (2022). Distinct MUNC lncRNA structural domains regulate transcription of different promyogenic factors.. Cell reports, 38(7), 110361. doi:10.1016/j.celrep.2022.110361

2021

Griffiths, C. D., Sweatt, A. J., & Janes, K. A. (2021). Simulating coxsackievirus B3 infection with an accessible computational model of its complete kinetics.. STAR protocols, 2(4), 100940. doi:10.1016/j.xpro.2021.100940

Janes, K. A. (2021). Ten simple rules for being a faculty advocate of first-year graduate students. PLOS COMPUTATIONAL BIOLOGY, 17(9). doi:10.1371/journal.pcbi.1009379

Lopacinski, A. B., Sweatt, A. J., Smolko, C. M., Gray-Gaillard, E., Borgman, C. A., Shah, M., & Janes, K. A. (2021). Modeling the complete kinetics of coxsackievirus B3 reveals human determinants of host-cell feedback.. Cell systems, 12(4), 304-323.e13. doi:10.1016/j.cels.2021.02.004

Sutcliffe, M. D., Galvao, R. P., Wang, L., Kim, J., Rosenfeld, L. K., Singh, S., . . . Janes, K. A. (2021). Premalignant Oligodendrocyte Precursor Cells Stall in a Heterogeneous State of Replication Stress Prior to Gliomagenesis. CANCER RESEARCH, 81(7), 1868-1882. doi:10.1158/0008-5472.CAN-20-1037

Schaff, D. L., Singh, S., Kim, K. -B., Sutcliffe, M. D., Park, K. -S., & Janes, K. A. (2021). Fragmentation of Small-Cell Lung Cancer Regulatory States in Heterotypic Microenvironments. CANCER RESEARCH, 81(7), 1853-1867. doi:10.1158/0008-5472.CAN-20-1036

Singh, S., Sutcliffe, M. D., Repich, K., Atkins, K. A., Harvey, J. A., & Janes, K. A. (2021). Pan-Cancer Drivers Are Recurrent Transcriptional Regulatory Heterogeneities in Early-Stage Luminal Breast Cancer. CANCER RESEARCH, 81(7), 1840-1852. doi:10.1158/0008-5472.CAN-20-1034

2020

Enriquez-Hesles, E., Smith, D. L., Maqani, N., Wierman, M. B., Sutcliffe, M. D., Fine, R. D., . . . Smith, J. S. (2020). A cell-nonautonomous mechanism of yeast chronological aging regulated by caloric restriction and one-carbon metabolism.. The Journal of biological chemistry, 296, 100125. doi:10.1074/jbc.ra120.015402

Enriquez-Hesles, E., Smith, D. L. J., Maqani, N., Wierman, M. B., Sutcliffe, M. D., Fine, R. D., . . . Smith, J. S. (2021). A cell-nonautonomous mechanism of yeast chronological aging regulated by caloric restriction and one-carbon metabolism. JOURNAL OF BIOLOGICAL CHEMISTRY, 296. doi:10.1074/jbc.RA120.015402

Pereira, E. J., Burns, J. S., Lee, C. Y., Marohl, T., Calderon, D., Wang, L., . . . Janes, K. A. (2020). Sporadic activation of an oxidative stress-dependent NRF2-p53 signaling network in breast epithelial spheroids and premalignancies. SCIENCE SIGNALING, 13(627). doi:10.1126/scisignal.aba4200

Nye, D. M. R., Albertson, R. M., Weiner, A. T., Hertzler, J. I., Shorey, M., Goberdhan, D. C. I., . . . Rolls, M. M. (2020). The receptor tyrosine kinase Ror is required for dendrite regeneration in Drosophila neurons. PLOS BIOLOGY, 18(3). doi:10.1371/journal.pbio.3000657

Janes, K. A. (2020). Fragile epitopes-Antibody's guess is as good as yours.. Science signaling, 13(616), eaaz8130. doi:10.1126/scisignal.aaz8130

Yao, M., Ventura, P. B., Jiang, Y., Rodriguez, F. J., Wang, L., Perry, J. S. A., . . . Zong, H. (2020). Astrocytic trans-Differentiation Completes a Multicellular Paracrine Feedback Loop Required for Medulloblastoma Tumor Growth. CELL, 180(3), 502-+. doi:10.1016/j.cell.2019.12.024

Schaff, D., Singh, S., Kim, K. -B., Sutcliffe, M., Park, K. -S., & Janes, K. (2020). Fragmentation of Small-cell Lung Cancer Regulatory States in Heterotypic Microenvironments. doi:10.1101/2020.03.30.017210

2019

Caulk, A. W., & Janes, K. A. (2019). Robust latent-variable interpretation of in vivo regression models by nested resampling.. Scientific reports, 9(1), 19671. doi:10.1038/s41598-019-55796-2

Smolko, C. M., & Janes, K. A. (2019). An ultrasensitive fiveplex activity assay for cellular kinases.. Scientific reports, 9(1), 19409. doi:10.1038/s41598-019-55998-8

Singh, S., Wang, L., Schaff, D. L., Sutcliffe, M. D., Koeppel, A. F., Kim, J., . . . Janes, K. A. (2019). In situ 10-cell RNA sequencing in tissue and tumor biopsy samples. SCIENTIFIC REPORTS, 9. doi:10.1038/s41598-019-41235-9

2018

Corliss, B. A., Ray, H. C., Patrie, J. T., Mansour, J., Kesting, S., Park, J. H., . . . Peirce, S. M. (2019). CIRCOAST: a statistical hypothesis test for cellular colocalization with network structures (vol 35, pg 506, 2019). BIOINFORMATICS, 35(4), 720-721. doi:10.1093/bioinformatics/bty797

Corliss, B. A., Ray, H. C., Patrie, J. T., Mansour, J., Kesting, S., Park, J. H., . . . Peirce, S. M. (2019). CIRCOAST: a statistical hypothesis test for cellular colocalization with network structures. BIOINFORMATICS, 35(3), 506-514. doi:10.1093/bioinformatics/bty638

Borten, M. A., Bajikar, S. S., Sasaki, N., Clevers, H., & Janes, K. A. (2018). Automated brightfield morphometry of 3D organoid populations by OrganoSeg. SCIENTIFIC REPORTS, 8. doi:10.1038/s41598-017-18815-8

2017

Bajikar, S. S., Wang, C. -C., Borten, M. A., Pereira, E. J., Atkins, K. A., & Janes, K. A. (2017). Tumor-Suppressor Inactivation of GDF11 Occurs by Precursor Sequestration in Triple-Negative Breast Cancer. DEVELOPMENTAL CELL, 43(4), 418-+. doi:10.1016/j.devcel.2017.10.027

Illendula, A., Gilmour, J., Grembecka, J., Tirumala, V. S. S., Boulton, A., Kuntimaddi, A., . . . Bushweller, J. H. (2017). Small Molecule Inhibitor of CBFβ-RUNX Binding for RUNX Transcription Factor Driven Cancers (vol 8, pg 117, 2016). EBIOMEDICINE, 25, 188. doi:10.1016/j.ebiom.2017.10.029

Shah, M., Smolko, C. M., Kinicki, S., Chapman, Z. D., Brautigan, D. L., & Janes, K. A. (2017). Profiling Subcellular Protein Phosphatase Responses to Coxsackievirus B3 Infection of Cardiomyocytes. MOLECULAR & CELLULAR PROTEOMICS, 16(4), S244-S262. doi:10.1074/mcp.O116.063487

Janes, K. A., Chandran, P. L., Ford, R. M., Lazzara, M. J., Papin, J. A., Peirce, S. M., . . . Lauffenburger, D. A. (2017). An engineering design approach to systems biology. INTEGRATIVE BIOLOGY, 9(7), 574-583. doi:10.1039/c7ib00014f

2016

Chitforoushzadeh, Z., Ye, Z., Sheng, Z., LaRue, S., Fry, R. C., Lauffenburger, D. A., & Janes, K. A. (2016). TNF-insulin crosstalk at the transcription factor GATA6 is revealed by a model that links signaling and transcriptomic data tensors.. Science signaling, 9(431), ra59. doi:10.1126/scisignal.aad3373

Janes, K. A., & VanHook, A. M. (2016). Science Signaling Podcast for 7 June 2016: Modeling signal integration.. Science signaling, 9(431), pc13. doi:10.1126/scisignal.aag1902

Illendula, A., Gilmour, J., Grembecka, J., Tirumala, V. S. S., Boulton, A., Kuntimaddi, A., . . . Bushweller, J. H. (2016). Small Molecule Inhibitor of CBFβ-RUNX Binding for RUNX Transcription Factor Driven Cancers. EBIOMEDICINE, 8, 117-131. doi:10.1016/j.ebiom.2016.04.032

Janes, K. A. (2016). Single-cell states versus single-cell atlases - two classes of heterogeneity that differ in meaning and method.. Current opinion in biotechnology, 39, 120-125. doi:10.1016/j.copbio.2016.03.015

Jensen, K. J., Moyer, C. B., & Janes, K. A. (2016). Network Architecture Predisposes an Enzyme to Either Pharmacologic or Genetic Targeting.. Cell systems, 2(2), 112-121. doi:10.1016/j.cels.2016.01.012

Pereira, E. J., Smolko, C. M., & Janes, K. A. (2016). Computational Models of Reactive Oxygen Species as Metabolic Byproducts and Signal-Transduction Modulators.. Frontiers in pharmacology, 7, 457. doi:10.3389/fphar.2016.00457

2015

Janes, K. A. (2015). Cell-to-Cell Transcript Variability: Seeing Signal in the Noise.. Cell, 163(7), 1566-1568. doi:10.1016/j.cell.2015.12.010

Janes, K. A. (2015). An analysis of critical factors for quantitative immunoblotting.. Science signaling, 8(371), rs2. doi:10.1126/scisignal.2005966

2014

Janes, K. A., & Wang, C. -C. (2014). Bringing systems biology to cancer, immunology and infectious disease.. Genome biology, 15(7), 407. doi:10.1186/s13059-014-0407-1

Wang, C. -C., Bajikar, S. S., Jamal, L., Atkins, K. A., & Janes, K. A. (2014). A time-and matrix-dependent TGFBR3-JUND-KRT5 regulatory circuit in single breast epithelial cells and basal-like premalignancies. NATURE CELL BIOLOGY, 16(4), 345-+. doi:10.1038/ncb2930

Bajikar, S. S., Fuchs, C., Roller, A., Theis, F. J., & Janes, K. A. (2014). Parameterizing cell-to-cell regulatory heterogeneities via stochastic transcriptional profiles. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(5), E626-E635. doi:10.1073/pnas.1311647111

Wang, C. -C., & Janes, K. A. (2014). Non-genetic heterogeneity caused by differential single-cell adhesion.. Cell cycle (Georgetown, Tex.), 13(14), 2149-2150. doi:10.4161/cc.29660

2013

Kang, B. H., Jensen, K. J., Hatch, J. A., & Janes, K. A. (2013). Simultaneous profiling of 194 distinct receptor transcripts in human cells.. Science signaling, 6(287), rs13. doi:10.1126/scisignal.2003624

Janes, K. A., & Lauffenburger, D. A. (2013). Models of signalling networks - what cell biologists can gain from them and give to them.. Journal of cell science, 126(Pt 9), 1913-1921. doi:10.1242/jcs.112045

Bose, A. K., & Janes, K. A. (2013). A high-throughput assay for phosphoprotein-specific phosphatase activity in cellular extracts.. Molecular & cellular proteomics : MCP, 12(3), 797-806. doi:10.1074/mcp.o112.024059

Jensen, K. J., Garmaroudi, F. S., Zhang, J., Lin, J., Boroomand, S., Zhang, M., . . . Janes, K. A. (2013). An ERK-p38 Subnetwork Coordinates Host Cell Apoptosis and Necrosis during Coxsackievirus B3 Infection. CELL HOST & MICROBE, 13(1), 67-76. doi:10.1016/j.chom.2012.11.009

Wang, L., & Janes, K. A. (2013). Stochastic profiling of transcriptional regulatory heterogeneities in tissues, tumors and cultured cells.. Nature protocols, 8(2), 282-301. doi:10.1038/nprot.2012.158

2012

Jensen, K. J., & Janes, K. A. (2012). Modeling the latent dimensions of multivariate signaling datasets.. Physical biology, 9(4), 045004. doi:10.1088/1478-3975/9/4/045004

Bajikar, S. S., & Janes, K. A. (2012). Multiscale Models of Cell Signaling. ANNALS OF BIOMEDICAL ENGINEERING, 40(11), 2319-2327. doi:10.1007/s10439-012-0560-1

2011

Janes, K. A. (2011). RUNX1 and its understudied role in breast cancer.. Cell cycle (Georgetown, Tex.), 10(20), 3461-3465. doi:10.4161/cc.10.20.18029

Wang, C. -C., Jamal, L., & Janes, K. A. (2012). Normal morphogenesis of epithelial tissues and progression of epithelial tumors.. Wiley interdisciplinary reviews. Systems biology and medicine, 4(1), 51-78. doi:10.1002/wsbm.159

Wang, L., Brugge, J. S., & Janes, K. A. (2011). Intersection of FOXO- and RUNX1-mediated gene expression programs in single breast epithelial cells during morphogenesis and tumor progression.. Proceedings of the National Academy of Sciences of the United States of America, 108(40), E803-E812. doi:10.1073/pnas.1103423108

2010

Garmaroudi, F. S., Marchant, D., Si, X., Khalili, A., Bashashati, A., Wong, B. W., . . . McManus, B. M. (2010). Pairwise network mechanisms in the host signaling response to coxsackievirus B3 infection.. Proceedings of the National Academy of Sciences of the United States of America, 107(39), 17053-17058. doi:10.1073/pnas.1006478107

Janes, K. A. (2010). Paring down signaling complexity.. Nature biotechnology, 28(7), 681-682. doi:10.1038/nbt0710-681

Janes, K. A., Wang, C. -C., Holmberg, K. J., Cabral, K., & Brugge, J. S. (2010). Identifying single-cell molecular programs by stochastic profiling.. Nature methods, 7(4), 311-317. doi:10.1038/nmeth.1442