Rice University
BioSciences at Rice

Aryeh Warmflash

Assistant Professor of BioSciences

Warmflash's Research

My research focuses on quantitative studies of signaling dynamics and spatial pattern formation during embryonic development and in the cancer microenvironment. My previous work has used live-cell signaling assays to show that the dynamics of the TGF-beta signaling pathway are adaptive and to explore the consequences of this discovery for the function of TGFbeta as a patterning signal. I have also used micropatterning technology to develop in vitro systems for studying pattern formation. In particular, I have demonstrated that human embryonic stem cells (hESCs) confined to micropatterns during differentiation form self-organized patterns containing all three germ layers and reminiscent of those in mammalian embryos.

Current projects include: using live-cell reporters of both signaling and fate in micropatterned culture to dissect the mechanisms of pattern formation, manipulating the shape of the micropatterned constraint to understand the relationship between geometry and cell fate, and developing three-dimensional culture systems that more completely mimic embryonic development. Ideas and tools developed for the study of embryonic development are also being deployed to understand the role of signaling dynamics and the relationship between healthy and diseased cells in the cancer microenvironment.

Select Publications

A. Nemashkalo, A. Ruzo, I. Heemskerk, and A. Warmflash Morphogen and community effects determine cell fates in response to BMP4 signaling in human embryonic stem cells.  Development, 144 2017: 3042 - 3053

I. Heemskerk, K. Burt, M. Miller, S. Chhabra, M. C. Guerra, and A. Warmflash. Morphogen dynamics control patterning in a stem cell model of the human embryo.   2017

A. S. Mahadevan, B. L. Long, C. W. Hu, D. T. Ryan, G. L. Britton, A. Ligeralde, A. Warmflash, J. T. Robinson, A. A. Qutub. cytoNet: analysis of cell communities.   2017

I. Heemskerk and A. Warmflash Pluripotent stem cells as a model for embryonic patterning: From signaling dynamics to spatial organization in a dish. .  Developmental Dynamics. , 245 2016: 976 - 990

A. Deglincerti, F. Etoc, M. C. Guerra, I. Martyn, J. Metzger, A. Ruzo, M. Simunovic, A. Yoney, A. H. Brivanlou, E. Siggia, and A. Warmflash . Self-organization of human embryonic stem cells on micropatterns.  Nature Protocols, 11 2016: 2223 - 2232

D. P. Noren, W. H. Chou, S. H. Lee, A. A. Qutub, A. Warmflash, D. S. Wagner, A. S. Popel, A. Levchenko VEGF-Mediated Ca2+ Signaling Steers Endothelial Cell Phenotypes by a Combination of Stochastic and Deterministic Decoding.  Science Signaling, 9(416):ra20 2016

A. Deglincerti, T. Haremaki, A. Warmflash, B. Sorre, and A. H. Brivanlou. Coco is a dual-activity modulator of TGFβ signaling. 2015. Development. 142:2678-2685.  PMCID: PMC4529031 [Available on 2016-08-01]

A. Warmflash, B. Sorre, F. Etoc, E. D. Siggia, and A. H. Brivanlou. A method to recapitulate early embryonic spatial patterning in human embryonic stem cells. 2014. Nature Methods. 11:847-854. PMCID: PMC4341966 

A. Warmflash, Q. Zhang, A. H. Brivanlou, and E. D. Siggia. "Controlling long-term signaling: receptor dynamics determine attenuation and refractory behavior of the TGF-β pathway"-Smad2/3 activity does not predict the dynamics of transcription. 2014. Science Signaling. 7:lc1

B. Sorre, A. Warmflash, A. H. Brivanlou, and E. D. Siggia. Encoding of temporal signals by the TGF-β pathway and implications for embryonic patterning. 2014. Developmental Cell. 30:334-342.  PMCID: PMC4165855 

M. Z. Ozair, S. Noggle, A. Warmflash, J. E. Krzyspiak, A. H. Brivanlou Smad7 directly converts human embryonic stem cells to telencephalic fate by a default mechanism.  Stem Cells , 31 2013: 35-47

A. Warmflash, Q. Zhang, B. Sorre, A. Vonica, E. D. Siggia, and A. H. Brivanlou Dynamics of TGF-β signaling reveal adaptive and pulsatile behaviors reflected in the nuclear localization of transcription factor Smad4.  Proc. Natl. Acad. Sci. , 109 2012: E1947-E1956

A. Warmflash, P. Francois, and E. D. Siggia Pareto evolution of gene networks: an algorithm to optimize multiple fitness objectives .  Phys. Biol. , 9 2012: 056001

A. Warmflash, E. D. Siggia and A. H. Brivanlou Signaling dynamics and embryonic development.  Cell Cycle, 11:2 2012

A. Warmflash, B. L. Arduini, and A. H. Brivanlou The molecular circuitry underlying pluripotency in embryonic stem cells.  Wiley Interdiscip. Rev. Syst. Biol. Med., 4 2012: 443-456

R. Sciammas*, Y. Li*, A. Warmflash*, Y Song, A. R. Dinner, and H. Singh An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling.  Mol. Syst. Biol., 7 2011: 495

M. Maienschein-Cline, A. Warmflash, and A. R. Dinner Defining cooperativity in gene regulation locally through intrinsic noise.  IET Syst. Biol., 4 2010: 379-392

M. Tchernookov, A. Warmflash, and A. R. Dinner Field theoretic treatment of an effective action for a model of catalyzed autoamplification.  Phys. Rev. E., 81 2010: 011112

A. Dickson, A. Warmflash, and A. R. Dinner Separating forward and backward pathways in nonequilibrium umbrella sampling.  J. Chem. Phys., 131 2009: 154104

M. Tchernookov, A. Warmflash, and A. R. Dinner Critical behavior of a model for catalyzed autoamplification.  J. Chem. Phys. , 130 2009: 134936

D. Reynaud, D. W. Lancki, J. M. R. Pongubala, A. Warmflash, A. R. Dinner, and H. Singh. Gene regulatory networks directing cell fates within the hematopoietic system.  Cell Determination during Hematopoiesis 2009

A. Warmflash and A. R. Dinner Modeling gene regulatory networks for cell fate specification.  Statistical Mechanics of Cellular Systems 2009

A. Dickson, A. Warmflash, and A. R. Dinner Nonequilibrium umbrella sampling in spaces of many order parameters.   J. Chem. Phys., 130 2009: 074104

A. Warmflash, D. N. Adamson, and A. R. Dinner The impact of the choice of noise statistics on models of enzyme kinetics.   J. Chem. Phys., 128 2008: 225101

A. Warmflash and A. R. Dinner Signatures of combinatorial regulation in intrinsic biological noise.  Proc. Natl. Acad. Sci., 105 2008: 17262-17267

A. Warmflash, P. Bhimalapuram, and A. R. Dinner Umbrella sampling for nonequilibrium processes.  J. Chem. Phys., 127 2007: 154112

A. Warmflash and A. R. Dinner A model for TCR gene segment use.  J. Immunol., 177 2006: 3857-3864

P. Laslo, C. Spooner*, A. Warmflash*, D. W. Lancki, H.-J. Lee, R. Sciammas, B. N. Gantner, A. R. Dinner and H. Singh Multilineage transcriptional priming and determination of alternate hematopoietic cell fates.  Cell, 126 2006: 755-766

A. Warmflash, M. Weigert and A. R. Dinner Control of genotypic allelic inclusion through TCR surface expression.  J. Immunol. , 175 2005: 6412-6419

Warmflash Website

  • B.A. Physics and Mathematics (2003) University of Pennsylvania
  • Ph.D. Physics (2008) University of Chicago
  • Department of Bioengineering
Research Areas
  • Signaling dynamics and spatial pattern formation during embryonic development and in the cancer microenvironment
Professional Experience
  • CPRIT Scholar in Cancer Research
    Rice University, BioSciences
Contact Information
Email: Aryeh.Warmflash@rice.edu
Phone: 713-348-2456
Office: Anderson Biological Labs, 344