BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Irudayaraj, Joseph MK
eRA COMMONS USER NAME
Professor of Biological Engineering
IRUDAYARAJJM
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
College of Engineering, Tamil Nadu, India
University of Hawaii, Honolulu, HI
University of Hawaii, Honolulu, HI
Purdue University, West Lafayette, IN
DEGREE
(if applicable)
YEAR(s)
FIELD OF STUDY
B.S.
M.S.
M.S.
Ph.D
1983
1986
1987
1990
Biosystems Engineering
Computer Sciences
Biosystems Engineering
Biological Engineering
A. PERSONAL STATEMENT
Our interest is in developing and applying single molecule tools for biomedical sciences research. We are
interested in monitoring the dynamics of nuclear proteins, transcripts, epigenetic mechanisms and signaling
pathways. Our group is involved in single cell experiments related to epigenetics, phosphorylation, toxicology,
and in developing biosensors. We have experience in designing peptide biosensors targeting kinase and
epigenome regulating proteins to assess cross talk between signaling and epigenetic regulation upon
contaminant exposure. We have successfully used our platform to monitor live cell acetylation in a range of
cancer cell lines exposed to chlorinated volatile organic compounds (VOCs) and drugs. In addition to
fluorescence imaging we have developed high-speed second harmonic generation and hyperspectral plasmon
super-resolution imaging strategies for quantifying mRNA, miRNA, and proteins in single cells in 3D cultures as
well as in tissues. We have extensively published on single-cell technologies and are a multidisciplinary group
and collaborate with the Departments of Biochemistry, Biological Sciences, Medicinal Chemistry, Basic
Medical Sciences, Veterinary Sciences and various Engineering programs on campus.
I am also the Deputy Director of Bindley Bioscience Center, Executive Committee member of the Purdue
Center for Cancer Research (Co-Leader of the Drug Discovery and Molecular Sensing Core of the Cancer
Center and co-PI of the P30 NIH-NCI Purdue Cancer Center grant) and Center for Food Safety Engineering
(2011-2015), 2011 Fellow of the Academic Leadership Program (Committee for Institutional Cooperation) and
2012 Fellow of Entrepreneurship Leadership Academy. I served as the Chair of the graduate program (20092012) of Purdue Agricultural and Biological Engineering (Rated #1 by US News and World Report 2009-2014)
and am the PI for a Keck Foundation grant.
Listing four key publications
1. Lee, K., Cui, Y., Lee, L., and Irudayaraj, J. 2014. Quantitative imaging of single mRNA splice variants in
living cells. Nature Nanotechnology. 9(6): 474-480.
2. Cui, Y. and Irudayaraj, J. 2015. Dissecting the behavior and function of MBD3 in DNA methylation
homeostasis by single-molecule spectroscopy and microscopy. Nucleic Acids Research. doi:
10.1093/nar/gkv098.
3. Vidi, P., Liu, J., Lelièvre, S., and Irudayaraj, J. 2014. Nanoscale localization microscopy reveals reduced
chromatin mobility in response to DNA damage in single live cells. Journal of Cell Science. doi:
10.1242/jcs.161885.
4. Damayanti, N., Parker, N., Irudayaraj, J. 2013. Fluorescence lifetime imaging of biosensor peptide
phosphorylation in live cells. Angewandte Chemie. 125: 4023-4026.
B. POSITION AND HONORS
Employment
1990 – 1994 Assistant Professor, Dept. Agric & Bioresource Engineering, University of Saskatchewan,
Saskatoon, Saskatchewan, Canada
1995 – 1998 Assistant Professor, Dept. Biological Engineering, Utah State University, Logan, UT
1998 – 2002 Assistant Professor, Dept. Agricultural & Biological Engineering, The Pennsylvania State
University, University Park, PA
2002 – 2005 Associate Professor, Materials Research Institute and Dept. Agricultural & Biological
Engineering, The Pennsylvania State University Park, PA
2004 – 2005 Visiting Associate Professor, Applied and Engineering Physics, Cornell University, Ithaca, NY
2005 – 2009 Associate Professor, Biological Engineering, Dept ABE, Purdue University, West Lafayette, IN
2009 – present Professor of Biological Engineering, Purdue University, WL, IN
2012 – present Professor of Mechanical Engineering (Courtesy), Purdue University, WL, IN
2012 – present Deputy Director of Bindley Bioscience Center, Discovery Park, Purdue University, WL, IN
Other Experience and Memberships
Professional
2005-present Council, Institute of Biological Engineers
2002-present Member, American Chemical Society; Biophysical Society; American Assoc. Clin Chem
University
1999-2004
Member, Materials Research Institute, The Pennsylvania State University
2005-present Co-director, Physiological Sensing Facility, Bindley Biosciences Center, Purdue Univ.
2007-present Co-director, Biophysics Core, Bindley Bioscience Center, Purdue Univ.
2007-present Member, Purdue Center for Cancer Research (PCCR), an NIH-NCI designated Center
2009-present Member, Strategic Advisory Committee to the Dean, College of Engineering
2012-present Co-Leader and Executive Committee, Drug Discovery and Molecular Sensing Core, PCCR
2009-2012
Chair, Graduate Program, Agricultural and Biological Engineering, Purdue University
Grant Review
2007-present Member NIH-IMST (Panel leader, 2010-present); NIH-Nano
2009-present CSR reviewer (2010-2012); T-RO1 and Challenge grants
2009-present NSF Career grants; NSF SBIR Programs (Biological Instrumentation Development)
2009
DoD, CDMRP Idea grants; USAMRMC, American Association for Advancement of Science;
2008Biomedical Research Council (Singapore); Medical Research Council (UK); BARD; NSERC
Honors and Awards
1996-1997
Teacher of the Year Award and Innovation in Teaching, Dept. Biological Engineering
2000
Young Engineer of the Year Award, 2000, Northeast Agric. & Biological Engineering Society
2003
USDA CSREES: Honor Award and Certificate for NE 179 Multistate Research Activity
2005,06,07,08 Best Paper Awards, American Society for Agric and Biological Engineers
2006, 07, 12 Seed for Success Award, Purdue University, Office of VP for Research
2009
University Faculty Scholar Merit Award, Purdue University
2011-12
CIC-ALP Leadership Fellow, Purdue University
2012-13
Entrepreneurship Leadership Academy
2014 Fellow, American Institute of Medical and Biological Engineers
2015
College of Engineering Research Excellence Award, Purdue University
C. CONTRIBUTION OF SCIENCE (Listing 5 key publications and 4 related peer reviewed publications)
1. His prior works (Nanoletters, 2007) formed the basis of commercial hyperspectral imaging
instrumentation development (Cytoviva, Inc.) that is presently being used to image nanoparticles’
localization and trafficking in cells. The company has already sold ~350 units around the world and
expects to sell ~500 units over the next 4-5 years. His recent work (Nature Nanotech, 2014) on the
quantification of proteins/RNAs in live cells has now opened up immense opportunities to monitor
intracellular protein/RNA dynamics/localization to understand cell function and for tissue screening at
the single cell level to provide quantitative information of protein/gene expression.
a. Lee, K., Cui, Y., Lee, L., and Irudayaraj, J. 2014. Quantitative imaging of single mRNA splice
variants in living cells. Nature Nanotechnology. 9(6): 474-480.
b. Liu, J., Cho, I-H., Cui, Y., and Irudayaraj, J. 2014. Second harmonic super-resolution
microscopy for quantification of mRNA at single copy resolution. ACS Nano, 8 (12): 12418–
12427.
c. Lee, K., Drachev, V., and Irudayaraj, J. 2011. DNA-Gold nanoparticle reversible networks grown
on cell surface marker sites: Application in Diagnostics. ACS NANO, 5(3): 2109-2117.
d. Yu, C. Naksharti, H., and Irudayaraj, J. 2007. Identity profiling of cell surface markers by
multiplex gold nanorod probes. Nano Letters, 7(8): 2300-2306.
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2. His group is the first to demonstrate live cell phosphorylation by fluorescence lifetime imaging (FLIM) in
single cells using peptide biosensors (Angew Chemie, 2013). Kinase activity is deregulated in diseases
and chemical contaminants. Their FLIM technology using specific kinase targeting peptide sensors sets
the stage for the dynamic monitoring of kinase activity and the subsequent signaling pathways in live
cells with information in the phosphorylation kinetics. The FLIM-based biosensor research has been
expanded to investigate phosphorylation dynamics during embryo development and vasculogenesis
(collaboration with Drs. Harbin and Freeman) critical for fetal development and to assess adverse
effects of contaminant exposures during development. Their discovery has formed the basis for the
development of a generalized live cell signaling pathway monitoring platform to monitor multiple
signaling pathways as a result of or in response to perturbation (physical or chemical) upstream.
a. Damayanti, N., Parker, N., Irudayaraj, J. 2013. Fluorescence lifetime imaging of biosensor
peptide phosphorylation in live cells. Angewandte Chemie. 125: 4023-4026.
b. Vidi, P., Liu, J., Lelièvre, S., and Irudayaraj, J. 2014. Nanoscale localization microscopy reveals
reduced chromatin mobility in response to DNA damage in single live cells. Journal of Cell
Science. doi: 10.1242/jcs.161885.
c. Vidi, P-A., Liu, J., Salles, D., Jayaraman, S., Dorfman, G., Gray, M., Abad, P., Moghe, P.,
Irudayaraj, J., Wiesmüller, L., and Lelièvre, S. 2014. NuMA promotes homologous
recombination repair by regulating the accumulation of the ISWI ATPase SNF2h at DNA breaks.
Nucleic Acids Research. 42(10):6365-79.
d. Chen, J., Nag, S., and Irudayaraj, J. 2011. Single molecule in vivo analysis of Toll-like 9 and
CpG DNA interaction. PLoS ONE. 6(4):e17991 (Pages. 1-10).
3. In live single cells their group is the first to reveal the stoichiometry of epigenetic proteins and their
activity in live cells using single molecule methods. More recently they have also revealed the efficacy
of Azacytidine on hydroxymethylation and have proposed the concept of varying effect of the
methylating drug depending upon the cell type. Their studies set the stage for monitoring
posttranslation modifications and their dynamic effect on transcription.
a. Cui, Y. and Irudayaraj, J. 2014. Dissecting the behavior and function of MBD3 in DNA
methylation homeostasis by single-molecule spectroscopy and microscopy. Nucleic Acids
Research. doi: 10.1093/nar/gkv098.
b. Cui, Y., Cho, I-H., Chowdhury, B., Irudayaraj, J. 2013. Real-time dynamics of methyl-CpGbinding domain protein 3 and its role in DNA demethylation by fluorescence correlation
spectroscopy. Epigenetics. 8(10): 1089-1100. (Epub ahead of print) (Cover Page article).
c. Chowdhury, B., Chen, J., Liu, S., Lossie, A., and Irudayaraj, J. 2014. Effect of AZA on
hydroxymethylation – exploring a novel effect. Nature Scientific Reports, doi:
10.1038/srep09281.
d. Chen, J., Miller, A., Kirchmaier, A., and Irudayaraj, J. 2012. Single Molecule Tools Elucidate
H2A.Z Nucleosome Composition. J. Cell Science. 125(12):2954-2964. PMID22393239
PMCIDPMC3434807
4. Their foundational work on the dynamics and accumulation of targeted nanoprobes in different cellular
compartments including the nucleus provides basic information on the time course of accumulation and
localization and diffusion in live cells. This information will be very useful for assessing the effect of
targeted therapy using nanomaterials.
a. Chen, J. and Irudayaraj, J. 2009. Quantitative investigation of compartmentalized dynamics of
ErbB2 targeting gold nanorods in live cells by single molecule spectroscopy. ACS Nano.
3:4071-4079. (highlighted as one of the top 10 papers in NIH-NCI Nanotechnology alliance).
b. Wang, Y., Chen, J., and Irudayaraj, J. 2011. Nuclear targeting dynamics of gold nanoclusters for
enhanced therapy of HER2+ breast cancer. ACS NANO. 5(12):9718-9725.
c. Wang, Y., Seebald, J., Szeto, D., and Irudayaraj, J. 2010. Biocompatibility and biodistribution of
surface-enhanced Raman scattering nanoprobes in zebrafish embryos in vivo and multiplex
imaging. ACS NANO. 4(7):4039-53.
d. Naik, G., Saha, B., Liu, J., Saber, S., Stach, E., Irudayaraj, J., Sands, T., Shalaev, V., and
Boltasseva, A. 2014. Epitaxial superlattices with titanium nitride as a plasmonic component for
optical hyperbolic metamaterials. Proceedings of the National Academy of Sciences 111
(21), 7546-7551.
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5. Quantification of transcripts, proteins, and whole cell using a variety of analytical tools capitalizing on
the enhancement possible by nanomaterials is an exquisite merit of nanotechnology. In their initial
work, a very low limit of detection was demonstrated for the quantification on BRCA1 mRNA. More
recently they have expanded this spectroscopy-based concept to colorimetric detection by lateral flow
immunochromatography technology. They have applied this concept to detect infectious pathogens,
cancer biomarker proteins, epigenetic modifications, and m/micro RNA.
a. Sun, L. and Irudayaraj, J. 2009. Quantitative Surface Enhanced Raman for gene expression
estimation, Biophysical Journal. 96:4609-16.
b. Chowdhury, B., Cho, I., Cui, Y., and Irudayaraj, J. 2014. Detection of 5mC, 5hmC, 5fC, and
5caC using a modified ELISA approach. Analytica Chimica Acta. DOI: 10.1016/j.aca.
2014.09.020.
c. Zhou, Z., Cho, I., Shan, Z., and Irudayaraj, J. 2015. Cross-platform detection of epigenetic
modifications from extracted chromatin in leucocytes from blood. Analytical Chemistry
Research, doi:10.1016/j.ancr.2015.04.002.
d. Cho, I., Bhunia, A., Irudayaraj, J. 2014. Rapid pathogen detection by lateral-flow
immunochromatographic assay with gold nanoparticle-assisted enzyme signal amplification.
International Journal of Food Microbiology. 206: 60-66.
D. RESEARCH SUPPORT
Live Single Cell Epigenetic Profiling and Regulation at Single Molecule Resolution.
Goal: The goal is to develop a single-cell platform to detect locus-specific DNA and histone modification in
single cells in a neural stem cell and in a 3D differentiating cancer cell model.
Keck Foundation
04/01/12-03/31/15
Role: PI (Co-PIs: Zhou, Lossie, Lelievre, and Kirchmaier)
5P30 CA23168-32 (Ratliff, PI)
09/08/10-06/30/15 [renewed]
NIH-NCI Cancer Center Support Grant
This is an institutional grant that supports the Purdue Center for Cancer Research programs and resources.
Role: Co-PI (as a Co-leader of one of the four cores of the Purdue Center for Cancer Research)
Center for Food Safety Engineering
06/01/2011 - 05/31/2016
Goal: The goals are to develop translational technologies for pathogen detection and separation to improve
food safety and security
USDA-Purdue University (Co-PI)
“Label-free real-time detection of kinase activity in vitro and in single cells using surface enhanced Raman
spectroscopy”
Goal: The goals are 1) to develop nanoparticles for detecting peptides by SERS, 2) monitor Abl kinase
phosphorylation in vitro, and 3) monitor phosphorylation dynamics in single cells.
NIH-NCI IMAT
07/01/11-06/30/16
Role: PI
“Single cell quantification of splice variants and epigenetic regulation of splicing”
Goal: The main goal is to detect splice variants in single cells using plasmon hyperspectral imaging. This
will also be extended to detect and quantify mRNA in single cells and eventually look at transcription.
NSF
08/01/12-07/31/16
Role: PI (Co-PI: Kirchmaier)
“Defining epigenetic programming during space flight expeditions in differentiating embryonic stem cells”
Goal: The goals are to examine the differential changes in hydroxymethylation under microgravity
conditions and to detect locus-specific hydroxymethylation events in single cells.
NASA
08/01/12-07/31/15
Role: PI (Co-PI: Lossie)
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“Nanobubble technology for ultrasound activated drug delivery”
Goals: We will develop an ultrasound tunable nanobubble for drug delivery. Preliminary proof in cancer will
be dmeonstarted.
Trask Foundation
01/04/2015 – 12/31/2015
Role: PI
Most Recently Completed:
“Functionalized Gold Nanoparticles as Surface-Enhanced Raman Scattering Substrates for Probing
Chromate Uptake in Single Cells”
Goal: The goals are to 1) develop a single-cell protocol for detecting chromate in single cells using surface
enhanced Raman spectroscopy, 2) develop an intracellular SERS platform to detect chromate reduction,
and 3) to monitor bioreduction in thin microbial films.
NIH-NIEHS-R01ES017066
01/01/09-12/31/14
Role: PI
Diagnosis Of Crystal-based Arthropathies Via Raman Spectroscopy
Goal: The key goals are to establish specific guidelines for the detection of Arthropathies and to develop a
portable Raman spectrometer for implementation in clinics for the detection of Arthropathies.
NIH-R01
09/01/2011 – 08/31/2014
Role: Consultant (PI: Akkus)
“Mapping Genomic Sites of 5-Hydroxymethylcytosine, a Novel CpG Modification Catalyzed by the MLL
Partner TET1 Protein Family”
Goal: Our goal is to examine the differential expression of hydroxymethylation and methylation and related
methyl binding proteins in differentiating cells.
Purdue Center for Cancer Research grant. Purdue University 12/01/10-06/30/14
Role: PI (Co-PI: Kirchmaier)
“Replication-coupled Chromatin Assembly And Epigenetic Processes In S. Cerevisiae”
Goal: The key goals are to develop a single-cell platform to detect co-localization of chromatin assembly
factors and the associated epigenetic modifications in a yeast model.
NSF
07/01/2011-06/30/2014
Role: Collaborator (PI: Kirchmaier)
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