gene icon
Using computational systems biology to map gene regulatory networks

 

gene regulation in mouse macrophages

Our lab uses computational and high-throughput experimental tools to understand gene regulatory networks and their roles in pathogenesis. A core area of emphasis is the innate immune system and its role in inflammation. With our network of collaborators, we aim to push the envelope on systems biology approaches to decipher the molecular basis of diseases and phenotypes.

Lab members

Stephen Ramsey Assistant Professor email show biosketch
portrait Stephen has a Ph.D. in physics from the University of Maryland and an Sc.B. in mathematical physics from Brown University. This quantitative background sparked an enduring interest in modeling and in scientific computing. Following his graduate studies, Stephen was a postdoctoral fellow at the University of Washington Genome Center, where he worked on genome mapping algorithms in Maynard Olson's laboratory. The Human Genome Project paved the way toward more molecular- and network-oriented research projects – primarily in the area of gene regulatory network modeling, analysis, and inference – in the labs of Hamid Bolouri and Ilya Shmulevich at the Institute for Systems Biology (ISB). Prior to joining OSU, Stephen was a senior scientist in Alan Aderem's laboratory at the Seattle Biomedical Research Institute, where his work on computational methods for mapping gene networks earned him a K25 Career Development Award from the National Institutes of Health. At OSU, Stephen holds a dual appointment in the Department of Biomedical Sciences and in the School of Electrical Engineering and Computer Science.
Mudra Choudhury Undergraduate Student email show biosketch
  Mudra is a University Honors College student majoring in BioResource Research with an option in Bioinformatics/Genomics.
Tanjin Xu Graduate Student email show biosketch
  Tanjin is a graduate student in Computer Science. Tanjin has a B.S. and an M.S. in Computer Science from Beihang University and he worked at IBM China before coming to OSU.
Alvin Yu Undergraduate Student email show biosketch
  Alvin is a University Honors College student majoring in Bioengineering. He is interested in improving the longevity and health of humans through research of diseases and gene regulatory networks.

Current Collaborators

  • Edward A. Fisher, New York University Medical Center
  • Shay Bracha, Oregon State University, College of Veterinary Medicine
  • Alan Aderem, Seattle Biomedical Research Institute
  • Harold Bae, Oregon State Univeristy, School of Biological and Population Health Sciences
  • Elain Fu, Oregon State University, School of Chemical, Biological & Environmental Engineering
  • Ilya Shmulevich, Institute for Systems Biology
  • Theo Knijnenburg, Institute for Systems Biology

Additional collaborators can be found as co-authors of articles on our Publications page.

Affiliations

What we do

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Our program combines computational and experimental approaches to map and functionally characterize gene regulatory networks. We are developing data-driven approaches to “reverse engineer” the networks that regulate cellular responses and that become dysregulated in disease. Of particular emphasis in our lab is the mammalian macrophage, a constituent of the innate immune system that plays important roles in host defense and in chronic inflammatory diseases such as atherosclerosis. A comprehensive understanding of immune regulatory networks is a gateway to being able to predict how the immune system will respond to novel therapies, pathogens, and vaccines. Through collaborations, we are also applying a systems biology approach to study gene regulation in smooth muscle cells and in certain types of cancer cells. On the computational side, we use statistical and machine-learning methods to both identify the genomic elements that regulate cellular gene expression and contextulalize the regulatory elements in a network. On the experimental side, we use the tools of systems biology, such as transcriptome and epigenome profiling, as a foundation for regulatory network inference.

Why we do it

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Advances in DNA sequencing are revolutionizing biomedicine by enabling comprehensive measurements of the cellular transcriptome and epigenome as well as genetic variation across the human population.. These advances are yielding immense amounts of data that promise unprecedented molecular insights into living systems, but efficiently extracting specific and testable biomolecular hypotheses from these heterogeneous data sets requires developing new mathematical and computational methods for data reduction and pattern discovery. These new methods must be able to take advantage of prior biological knowledge about molecular pathways, interaction networks, and disease associations. In the context of the innate immune system, the methods that we are developing have the potential to uncover novel molecular regulators of inflammation and host responses to pathogens. In the long-term, it is envisioned that such novel regulators could lead to new therapeutic targets and approaches to chronic and/or infectious diseases.

Recent News

Feb. 26, 2015Our collaboration's' article on smooth muscle foam cells is the online "Editor's Pick" for March 2015 and it is highlighted in an editorial in the March edition of ATVB!
Mar. 4, 2015Ilya Shmulevich visited from the Institute for Systems Biology.
Mar. 6, 2015Stephen gave a guest lecture on genetic variation in BB485/585.

Upcoming

April. 3, 2015First day of VMB 670, a new course on systems biology and bioinformatics.

News Archive

Jan. 20, 2015Dan Zak visits from Seattle Biomedical Research Institute.
Jan. 15, 2015Stephen gave a research presentation at the Institute for Systems Biology in Seattle.
Dec. 24, 2014Our jointly authored paper on smooth muscle foam cells (with Ed Fisher's lab at NYU, Joe Miano's lab at U. Rochester, Xiaochun Long's lab at Albany Medical College, Fernando Martinez's lab at Oxford, and Kathryn Moore's lab at NYU) has been accepted for publication by Arteriosclerosis, Thrombosis, and Vascular Biology.
Dec. 23, 2014Mudra's research grant proposal has been funded under the URISC program (one of only nine awards made, university-wide). Congratulations, Mudra, and thank you for your support, OSU Research Office!
Dec. 5, 2014Stephen gave a seminar on systems biology in the course Z507, What is systems biology?
Dec. 4, 2014Our manuscript (with co-authors at Seattle BioMed and NYU) on a systems biology approach to studying gene regulation in atherosclerosis regression has been published in PLoS Genetics.
Dec. 1, 2014Stephen gave a lecture on systems biology in the BRR100 seminar series.
Sep. 16, 2014Stephen served on a panel discussion for the MCB 525 course "Quantitative Biology".
Nov. 20, 2014Both Alvin Yu and Mudra Choudhury have been awarded DeLoach Work Scholarships from the University Honors College. Congratulations! And thank you, for your support, UHC!
Nov. 19, 2014Stephen gave a presentation on bioinformatics and genomics in VMB671.
Oct. 21, 2014Tanjin Xu has joined the lab. Welcome, Tanjin!
Sep. 12, 2014        Alvin Yu's poster on his drug repurposing project was the winner of the Poster Award for the undergraduate student category, at the OSU CGRB Fall Conference. Congratulations, Alvin!
Aug. 28, 2014        Stephen gave a research presentation at the summer workshop "Genetic, epigenetic, and functional aspects of complex diseases IV" at the University of Eastern Finland.
Aug. 27, 2014Stephen gave a research seminar at the University of Tampere in Finland.
Jun. 17-19, 2014Stephen presented a poster on Holly Arnold's work on machine learning for biological network analysis, at the conference Systems Biology of Human Disease 2014 in Boston.
May 28, 2014Stephen was a guest instructor in the course Molecular Host-Microbe Interactions, MCB 637.
May 4, 2014Stephen gave an invited talk on systems biology at the Pediatrics Academic Societies meeting in Vancouver, British Columbia.
Apr. 28, 2014Mudra Choudhury has joined the lab. Welcome, Mudra!
Apr. 14, 2014Manuscript "Multiscale representation of genomic signals" has been published online in Nature Methods (with Theo Knijnenburg, Ilya Shmulevich, and colleagues at Institute for Systems Biology and collaborators at TU-Delft, NKI, USC, and UCLA).
Apr. 7, 2014Stephen gave a presentation entitled "An integrative computational systems biology approach to mapping gene regulatory networks" at the 2014 CGRB Spring Conference at OSU.
Mar. 16, 2014Alvin Yu has joined the lab. Welcome, Alvin!
Dec. 2013The Molecular and Cellular Biology Program has approved Stephen's appointment to their graduate faculty.
Dec. 2013Laboratory renovations of the first floor in Dryden Hall are complete, and as a result, we now have our lab space on the third floor of Dryden Hall.
Oct. 2013The Center for Genome Research and Biocomputing has designated Stephen as a CGRB faculty affiliate.
Sep. 2013The lab website is up and running, at lab.saramsey.org.
May 2013Stephen gives an invited talk at the McGill Systems Biology Atherosclerosis Symposium in Montréal, Québec.

Peer-Reviewed Publications

Reference Title Author(s) Link
Bioinform Biol Insights.
in press (2015)
Reverse enGENEering of regulatory networks from Big Data: a guide for a biologist Dong X, Yambartsev A, Ramsey SA, Thomas L, Shulzhenko N, Morgun A  
EMBO J.
in press (2015)
An LXR-NCOA5 complex directs inflammatory crosstalk-dependent repression of cholesterol efflux Gillespie MA, Gold E, Ramsey SA, Podolsky I, Aderem A, Ranish J  
Arterioscler Thromb Vasc Biol.
35:535-546 (2015)
Cholesterol loading re-programs the miR-143/145-myocardin axis to convert aortic smooth muscle cells to a dysfunctional macrophage-like phenotype Vengrenyuk Y, Nishi H, Long X, Ouimet M, Savji N, Martinez FO, Cassella C, Moore KJ, Ramsey SA, Miano JM, Fisher EA [link]
Featured in editorial
PLoS Genetics.
10(12):e1004828 (2014)
Epigenome-guided analysis of the transcriptome of plaque macrophages during atherosclerosis regression reveals activation of the Wnt signaling pathway Ramsey SA*, Vengrenyuk Y*, Menon P, Podolsky I, Feig JE, Aderem A, Fisher EA, Gold ES [link]
Nature Methods.
11(6):689-694 (2014)
Multiscale representation of genomic signals Knijnenburg TA, Ramsey SA, Berman BP, Kennedy KA, Smit AFA, Wessels LFA, Laird PW, Aderem A, Shmulevich I [link]
PLoS ONE.
8(3):e57837 (2013)
Urokinase plasminogen activator induces pro-fibrotic/M2 phenotype in murine cardiac macrophages Meznarich J, Malchodi L, Helterline D, Ramsey SA, Bertko K, Plummer T, Plawman A, Gold E, Stempien-Otero A [link]
J Exp Med.
209(4):807-817 (2012)
ATF3 protects against atherosclerosis by suppressing 25-hydroxycholesterol-induced lipid body formation Gold ES*, Ramsey SA*, Sartain MJ, Selinummi J, Podolsky I, Rodriguez DJ, Moritz RL, Aderem A [link]
Mol Syst Biol.
8:577 (2012)
Asymmetric positive feedback loops reliably control biological responses Ratushny AV, Saleem RA, Sitko K, Ramsey SA, Aitchison JD [link]
J Biol Chem.
286:22665-22677 (2011)
Mechanisms of urokinase plasminogen activator (uPA)-mediated atherosclerosis: Role of the uPA receptor and S100A8/A9 proteins Farris SD, Hu JH, Krishnan R, Emery I, Chu T, Du L, Kremen M, Dichek HL, Gold E, Ramsey SA, Dichek DA [link]
Methods Mol Biol. 781:415-33 (2011) Mathematical modeling of biomolecular network dynamics Ratushny AV, Ramsey SA, Aitchison JD [link]
Microfluid Nanofluid.
10(1):29-35 (2011)
Transport in two-dimensional paper networks Fu E, Ramsey SA, Kauffman P, Lutz B, Yager P [link]
Analyt. Chem.
83(20):7941-7946 (2011)
Enhanced sensitivity of lateral flow tests using a two-dimensional paper network format Fu E, Liang T, Houghtaling J, Ramachandran S, Ramsey SA, Lutz B, Yager P [link]
J Cell Sci.
123(Pt 20):3558-65 (2010)
ATF3, an adaptive-response gene, enhances TGFβ signaling and cancer-initiating cell features in breast cancer cells Yin X, Wolford CC, Chang YS, McConoughey SJ, Ramsey SA, Aderem A, Hai T [link]
Bioinformatics.
26(17):2071-5 (2010)
Genome-wide histone acetylation data improve prediction of mammalian transcription factor binding sites Ramsey SA, Knijnenburg TA, Kennedy KA, Zak DE, Gilchrist M, Gold ES, Johnson CD, Lampano AE, Litvak V, Navarro G, Stolyar T, Aderem A, Shmulevich I [link]
Corrected supplement. doc.
BMC Bioinform.
11:377 (2010)
SeqAdapt: an adaptable system for the tracking, storage, and analysis of high-throughput sequencing experiments Burdick DB, Cavnor CC, Handcock J, Killcoyne S, Lin J, Marzolf B, Ramsey SA, Rovira H, Bressler R, Shmulevich I, Boyle J [link]
EMBO Mol Med.
2(3):79-89 (2010)
A systems biology approach to understanding atherosclerosis Ramsey SA, Gold ES, Aderem A [link]
Analyt Chem.
81(9):3407-13 (2009)
Modeling of a competitive microfluidic heterogeneous immunoassay: sensitivity of the assay response to varying system parameters Fu E, Nelson KE, Ramsey SA, Foley JO, Helton K, Yager P [link]
Nature Immunol.
10(4):437-43 (2009)
Function of C/EBPδ in a regulatory circuit that discriminates between transient and persistent TLR4-induced signals Litvak V, Ramsey SA, Rust AG, Zak DE, Kennedy KA, Lampano AE, Nykter M, Shmulevich I, Aderem A [link]
Proc Natl Acad Sci U S A.
106(10):3758-63 (2009)
Dynamic analysis of MAPK signaling using a high-throughput microfluidic single-cell imaging platform Taylor RJ, Falconnet D, Niemistö A, Ramsey SA, Prinz S, Shmulevich I, Galitski T, Hansen CL [link]
Biophys J.
95(8):3715-23 (2008)
Control of transcriptional variability by overlapping feed-forward regulatory motifs Ratushny AV*, Ramsey SA*, Roda O, Wan Y, Smith JJ, Aitchison JD [link]
PLoS Comp Biol.
4(3):e1000021 (2008)
Uncovering a macrophage transcriptional program by integrating evidence from motif scanning and expression dynamics Ramsey SA, Klemm SL, Zak DE, Kennedy KA, Thorsson V, Li B, Gilchrist M, Gold ES, Johnson CD, Litvak V, Navarro G, Roach JC, Rosenberger CM, Rust AG, Yudkovsky N, Aderem A, Shmulevich I [link]
Corrected
Table S17.
Proc Natl Acad Sci U S A.
105(6):1897-1900 (2008)
Gene expression dynamics in the macrophage exhibit criticality Nykter M, Price ND, Aldana M, Ramsey SA, Kauffman SA, Hood L, Yli-Harja O, Shmulevich I [link]
Analyt Chim Acta.
599(1):118-23 (2007)
Dependence of the signal amplification potential of colloidal gold nanoparticles on resonance wavelength in surface plasmon resonance-based detection Fu ES, Ramsey SA, Yager P [link]
Mol Syst Biol.
3:115 (2007)
Transcriptional responses to fatty acid are coordinated by combinatorial control Smith JJ, Ramsey SA, Marelli M, Marzolf B, Hwang D, Saleem RA, Rachubinski RA, Aitchison JD [link]
PLoS ONE
2:e249 (2007)
Control of signaling in a MAP-kinase pathway by an RNA-binding protein Prinz S, Aldridge C, Ramsey SA, Taylor RJ, Galitski T [link]
Sens Act B Chem. 123(10):606-13 (2007) Resonance wavelength-dependent signal of absorptive particles in surface plasmon resonance-based detection Fu E, Ramsey SA, Chen J, Chinowsky TM, Wiley B, Xia Y, Yager P [link]
Rev Sci Inst.
77:076106 (2006)
One-dimensional surface plasmon resonance imaging system using wavelength interrogation Fu E, Ramsey SA, Thariani R, Yager P [link]
Nature Genetics.
38(9):1082-7 (2006)
Dual feedback loops in the GAL regulon suppress cellular heterogeneity in yeast Ramsey SA, Smith JJ, Orrell D, Marelli M, Petersen TW, de Atauri P, Bolouri H, Aitchison JD [link]
Corrected supplementary note.
Physica D.
217(1):64-76 (2006)
Feedback control of stochastic noise in the yeast galactose utilization pathway Orrell D, Ramsey S, Marelli M, Smith JJ, Petersen TW, de Atauri P, Aitchison JD, Bolouri H [link]
Philos Trans R Soc Lond B Biol Sci.
361(1467):495-506 (2006)
Transcriptional noise and cellular heterogeneity in mammalian macrophages Ramsey S, Ozinsky A, Clark A, Smith KD, de Atauri P, Thorsson V, Orrell D, Bolouri H [link]
Proc Natl Acad Sci U S A.
102(48):17296-17301 (2005)
A data integration methodology for systems biology Hwang D, Rust AG, Ramsey S, Smith JJ, Leslie DM, Weston AD, de Atauri P, Aitchison JD, Hood L, Siegel AF, Bolouri H [link]
Proc Natl Acad Sci U S A.
102(48):17302-17307 (2005)
A data integration methodology for systems biology: experimental validation Hwang D, Smith JJ, Leslie DM, Weston AD, Rust AG, Ramsey S, de Atauri P, Siegel AF, Bolouri H, Aitchison JD, Hood L [link]
J Bioinform Comp Biol.
3(2):415-436 (2005)
Dizzy: Stochastic simulations of large-scale genetic regulatory networks Ramsey S, Orrell D, Bolouri H [link]
(Supplement: [link])
Bioinformatics.
21(2):208-217 (2005)
A method for estimating stochastic noise in large genetic regulatory networks Orrell D, Ramsey S, de Atauri P, Bolouri H [link]
Biochem J.
387:77-84 (2005)
Is the regulation of galactose-1-phosphate tuned against gene expression noise? de Atauri P, Orrell D, Ramsey S, Bolouri H [link]
Syst Biol (Stevenage).
1(1):28-40 (2004)
Evolution of "design" principles in biochemical networks de Atauri P, Orrell D, Ramsey S, Bolouri H [link]

 

Peer-Reviewed Publications (Physics)

Reference Title Author(s) Link
Int J Theo Phys.
40(12):2231-58 (2001)
Interacting field theories in Robertson-Walker spacetimes: analytic approximations Molina-Paris C, Anderson PR, Ramsey SA [link]
Phys Rev D.
61:127501 (2000)
One-loop λφ4theory in Robertson-Walker spacetimes: adiabatic regularization and analytic approximation Molina-Paris C, Anderson PR, Ramsey SA [link]
Phys Rev D.
61:125013 (2000)
Hydrodynamic transport functions from quantum kinetic theory Calzetta EA, Hu BL, Ramsey SA [link]
Phys Rev D.
59:045009 (1999)
Defect formation and Critical Dynamics in the Early Universe Stephens GJ, Calzetta EA, Hu BL, Ramsey SA [link]
Int J Theo Phys.
38(4):1299-1314 (1999).
Nonequilibrium dynamics of quantum fields in inflationary cosmology Ramsey SA [link]
Phys Rev D.
57:6003-6021 (1998)
Nonequilibrium inflaton dynamics and reheating. II. Fermion production, noise, and stochasticity Ramsey SA, Hu BL, Stylianopoulos AM [link]
Phys Rev D.
56:678-705 (1997); Erratum-ibid 57:3798 (1998)
Nonequilibrium inflaton dynamics and reheating: Back reaction of parametric particle creation and curved spacetime effects Ramsey SA, Hu BL [link]
Phys Rev D.
56:661-677 (1997)
O(N) Quantum fields in curved spacetime Ramsey SA, Hu BL [link]

 

Other Publications or Works

Reference Title Author(s) Link
U.S. Patent no. 7555542 (2009) Method and system for directing requests for content to a content server based on network performance. Ayers M, Black BJ, Brown C, Carlson J, Cohn D, Laird S, Miller J, Ronen O, Schachter P, Stiffelman O, Ramsey S  
U.S. Patent no. 6981055 (2005) Method and system for optimizing routing through multiple available Internet route providers. Ahuja A, Ayers M, Black B, Brown C, Cohn DT, Ramsey S, Ronen O, Schachter PJ, Stiffelman OB, Wheeler CD  
Doctoral Dissertation, University of Maryland (1997) Nonequilibrium dynamics of quantum fields in inflationary cosmology Ramsey SA (PhD advisor: Bei-Lok Hu) [arXiv]
Brown University Physics Report BROWN-HET-922 (1993) Some statistics for measuring large-scale structure Brandenberger RH, Kaplan DM, Ramsey SA [arXiv]

* indicates that these authors contributed equally.

You can also find our list of publications on Google Scholar.

Teaching Overview

My teaching interests broadly encompass bioinformatics, computational biology, machine-learning applications in the life sciences, and biocomputational modeling. I am particularly excited about mentoring undergraduate and graduate students in research projects in computational biology, to enable students to connect their computational and engineering skills to compelling life sciences applications.

Current and future teaching

Spring 2015 Co-Instructor VMB670 Systems Biology and Bioinformatics
(Instructors: Stephen Ramsey, Natalia Shulzhenko, Jan Medlock, and Andrey Morgun)
Fall 2015 Instructor CS446 Biological Networks    (Category 2 proposal pending)

Past teaching

Winter 2014 Guest Instructor VMB631 Mathematical modeling of biological systems (Instructor: Jan Medlock)
Winter 2014 Guest Lecturer BB499 Applied Bioinformatics (Instructor: David Hendrix)
Spring 2014 Guest Lecturer MCB637 Molecular host-microbe interactions (Lead Instructor: Virginia Weis)
Fall 2014 Guest Speaker MCB525 Quantitative biology (Lead Instructor: Kelly Vining)
Fall 2014 Instructor CS419/519 Selected Topics in Computer ScienceNetwork Methods in Bioinformatics
Fall 2014 Guest Lecturer VMB671 Molecular Tools (Instructor: Claudia Häse)
Fall 2014 Seminar Speaker Z507 What is Systems Biology (Organized by the OSU SSIMBio consortium)
Fall 2014 Guest Speaker BRR100 Great experiments (Instructor: Wanda Crannell)
Winter 2015 Co-Instructor MCB555 Genome Expression
Winter 2015 Guest lecturer BB485/585 Applied Bioinformatics (Instructor: David Hendrix)
 

Software and tools

  • Code for our 2008 article on using the time-lagged correlation to analyze time-course gene expression data.

Supplementary material for lab publications

Links at OSU

Here are some links to other web sites of interest at OSU:

Graduate programs that we work with

The Ramsey Lab can mentor graduate students in Computer Science, Electrical Engineering, Molecular and Cellular Biology, or Comparative Health Sciences, and potentially other programs through special arrangement. The application process for incoming PhD students for fall 2015 has concluded. New opportunities for graduate students will be listed here as they arise.

Compbio @ OSU

Our lab bridges the Department of Biomedical Sciences and the School of Electrical Engineering and Computer Science, and we interact with students and researchers from diverse areas of the life sciences and from computer science, statistics, and engineering. The academic environment for interdisciplinary collaborations in computational biology at OSU is outstanding, with the Center for Genome Research and Biocomputing (CGRB) serving as a hub for computational infrastructure, training, collaboration, and genomics core facilities. Computational biology researchers at OSU interact frequently to share ideas, though CGRB-sponsored seminars, bioinformatics user group meetings, training sessions, and twice-yearly computational biology / genomics workshops. Biocomputing is a rapid growth area for OSU, with four faculty hired in this area during 2013 and additional biocomputing hires planned in the near future. Your research will be powered by the bioinformatics computing cluster in the Center for Genome Research and Biocomputing (CGRB) and the 16 TFLOPS high-performance computing system in the College of Engineering.

About Corvallis

Our lab is located on the OSU campus in Corvallis, a dynamic, intellectually rich, and bike-friendly university setting in the beautiful Willamette Valley of Oregon. Corvallis is renowned for access to outdoor recreation and for quality-of-life. In addition to the thriving social and intellectual environment in Corvallis, the city of Eugene (which hosts the University of Oregon) is only 50 minutes away, and Portland (which hosts Reed College, the Oregon Health and Sciences University, and Portland State University) is only 90 minutes away. Charming coastal communities like Newport (where the Hatfield Marine Science Center is located), are only an hour away. For more information about Oregon State University, see the OSU website.

We value diversity

Oregon State University is an Equal Opportunity Employer and the Ramsey Lab respects and values diversity in the workplace.

Telephone

Office (Biomedical Sciences)

Laboratory

Office (Computer Science)

U.S. Post

Stephen Ramsey
Oregon State University
Department of Biomedical Sciences
106 Dryden Hall
Corvallis, OR 97331-4801

UPS/Fedex

Stephen Ramsey
Oregon State University
Department of Biomedical Sciences
105 Magruder Hall
Corvallis, OR 97331-4801

Department fax

541.737.2730  

Secure email contact info

 

* Email message strongly preferred over voicemail

‡ Emailed PDF is recommended instead of fax

© 2013–2015 Stephen Ramsey.    The orange OSU logo is a trademark of Oregon State University and is used with permission.