Principal Investigator/Program Director (Last, First, Middle):

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

Venugopalan, Vasan

Professor of Chemical Engineering, Biomedical Engineering, and Surgery

eRA COMMONS USER NAME

vasannih EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION

University of California, Berkeley, CA M.I.T., Cambridge, MA Harvard Medical School, Boston, MA Princeton University, Princeton, NJ University of California, Irvine, CA

DEGREE (if applicable)

B.S. S.M., Sc.D. post-doc post-doc post-doc

YEAR(s)

FIELD OF STUDY

1988 1990, 1994 1994-1995 1995-1996 1996-1998

Mechanical Engineering Mechanical Engineering Biomedical Optics Biophysics Biomedical Optics

A. Personal Statement My research interests lie in two principles areas: (a) the analysis and application of the mechanisms that mediate the transport and interaction of laser microbeam radiation with tissues, cells, and polymers and (b) the development of mathematical and computation methods to model the propagation of light in cells and tissues spanning microscopic to macroscopic length scales. Laser Microbeam Interactions: Applications range from the development and analysis of functional imaging and diagnostic methods in cells and tissues, the use of pulsed laser microbeam irradiation for cellular microsurgery, bioanalytical and perturbative methods in molecular and cell biology and biotechnology, and the integration of biophotonic methods with analytic microdevices and microfluidics. An important focus of my group’s work is development of model-based predictions that can be verified by experiment and establishes connections between the physical characteristics of biophotonic phenomena and subsequent biological outcome. Such predictions are critical for the efficient design and robust application of novel biophotonic technologies. Major achievements include establishing optical breakdown (plasma formation) as the key process governing laser microsurgery (pub [18] below with >150 citations), authoring (w/ Alfred Vogel) the seminal reference on pulsed laser ablation of biological tissues (pub [19] with >900 citations), establishing the principal role of cavitation bubble dynamics in laser microbeam cell lysis and molecular delivery (pubs [22, 32, 39]) and pioneering the integration of laser microbeam irradiation with microfluidics for applications in cell biology and bioanalytics (pubs [40, 41, 42, 46]). Computational Biophotonics: Since 2008, I have led the newly-founded Virtual Photonics Technology Core which has a dual role of advancing state of the art computational methods while also developing an opensource software platform known as the Virtual Tissue Simulator (VTS), to enable a broad class of students and researchers utilize these tools via dissemination vehicles that are appropriate based on their expertise and sophistication. Major achievements in the area of Computational Biophotonics include: (a) developing a novel framework for analysis of light transport in tissues on mesoscopic spatial scales (pubs [12] with >80 citations, [24. 38]); (b) development and validation of perturbation and differential Monte Carlo methods for analysis of superficial tissue volumes (pubs [17] with >70 citations, [33]); (c) development of hybrid electric-field Monte Carlo and diffraction modeling framework to compute focused beam propagation in turbid media (pubs [44, 47]); and (d) development of improved scaled and spatial frequency domain Monte Carlo methods (pubs [48, 49]).

B. Positions and Honors 1998–present: University of California, Irvine, Assistant Professor (1998-2005), Associate Professor (2005-09) and Full Professor (2009-), Departments of Chemical Engineering & Materials Science, Biomedical Engineering, and Surgery (Beckman Laser Institute). 2009-present: Associate Editor, Optics Express PHS 398/2590 (Rev. 09/04, Reissued 4/2006)

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Principal Investigator/Program Director (Last, First, Middle):

2010-present: Associate Editor, Biomedical Optics Express Member: American Association for the Advancement of Science, The American Society of Mechanical Engineers, SPIE, The International Society for Optical Engineering, The Optical Society of America

C. Selected Peer-reviewed publications (in chronological order; 27 chosen from 56 total, hindex=26). [8] [12]

[16]

[17]

[18] [19] [22] [23]

[32]

[33]

[34] [36]

[37] [38] [39] [40]

[41]

Venugopalan, V., N. S. Nishioka and B. B. Miki´c. Thermodynamic response of soft biological tissues to pulsed infrared laser irradiation. Biophysical Journal, 70(6): 2983–2996, (1996). V. Venugopalan, J. S. You and B. J. Tromberg. Radiative transport in the diffusion approximation: An extension for highly absorbing media and small source detector separations. Physical Review E, 58(2):2395–2407, (1998). Berns, M. W., Z. Wang, A. K. Dunn, V. P. Wallace and V. Venugopalan. Gene inactivation by multiphoton-targeted photochemistry. Proceedings of the National Academy of Sciences USA, 97(17):9504–9507, (2000). C. K. Hayakawa, J. Spanier, F. Bevilacqua, A. K. Dunn, J. S. You, B. J. Tromberg and V. Venugopalan. Perturbation Monte Carlo methods to solve inverse photon migration problems in heterogeneous tissues. Optics Letters, 26(17):1335–1337, (2001). Venugopalan, V., A. Guerra III, K. Nahen and A. Vogel. On the role of laser-induced plasma formation in pulsed laser microsurgery and micromanipulation. Physical Review Letters, 88(7):078103, (2002). Vogel, A. and V. Venugopalan. Mechanisms of pulsed laser ablation of tissue. Chemical Reviews, 103(2):577–644, (2003). Rau, K. R., A. Guerra III, A. Vogel and V. Venugopalan. Investigation of laser-induced cell lysis using time-resolved imaging. Applied Physics Letters, 84(15):2940–2942, (2004). Carp, S. A., S. A. Prahl and V. Venugopalan. Radiative transport in the delta-P1 approximation: Accuracy of fluence rate and optical penetration depth predictions in turbid semi-infinite media. Journal of Biomedical Optics, 9(3):632–647, (2004). Rau, K. R., P. A. Quinto-Su, A. N. Hellman and V. Venugopalan. Laser microbeam induced cell lysis: Time-resolved imaging and analysis of hydrodynamic effects. Biophysical Journal, 91(1):317–329, (2006). Seo, I., J. S. You, C. K. Hayakawa and V. Venugopalan. Perturbation Monte Carlo methods for measurement of optical properties in a layered epithelial tissue model. Journal of Biomedical Optics, 12(1):014030 (15 pages), (2007). Hellman, A. N., K. R. Rau, H. H. Yoon, S. Bae, J. F. Palmer, N. L. Allbritton and V. Venugopalan. Laserinduced mixing in microfluidic channels. Analytical Chemistry, 79(12):4484–4492, (2007). Hayakawa, C. K., J. Spanier, and V. Venugopalan. Coupled forward-adjoint Monte Carlo simulations of radiative transport for the study of optical probe design in heterogeneous tissues. SIAM Journal of Applied Mathematics. 68(1):253–270, (2007). Carp, S A. and V. Venugopalan. Optoacoustic imaging based on the interferometric measurement of surface displacement. Journal of Biomedical Optics, 12(6):064001, (2007). Seo, I., C. K. Hayakawa and V. Venugopalan. Radiative transport in the delta-P1 approximation for semi-infinite turbid media. Medical Physics, 35(2):681–693, (2008) Hellman, A. N., K. R. Rau, H. H. Yoon and V. Venugopalan. Biophysical response to laser microbeaminduced cell lysis and molecular delivery. Journal of Biophotonics, 1(1):24–35, (2008). Quinto-Su, P. A., H-H. Lai, H. H. Yoon, C. E. Sims, N. L. Allbritton and V. Venugopalan. Examination of laser microbeam cell lysis in a PDMS microfluidic channel using time-resolved imaging. Lab on a Chip, 8(3):408–414, (2008). (PMCID: PMC2525503) Quinto-Su, P. A., G. T. Salazar, C. E. Sims, N. L. Allbritton and V. Venugopalan. Mechanisms of pulsed laser microbeam release of SU-8 polymer “micropallets” for the collection and separation of adherent cells. Analytical Chemistry, 80(12):4675–4679, (2008). (PMCID: PMC2525502)

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[44] C. K. Hayakawa, V. Venugopalan, V. V. Krishnamachari and E. O. Potma. Amplitude and phase of tightly focused laser beams in turbid media. Physical Review Letters, 103(4):043903 (4 pages), (2009) (PMCID: PMC2850562). [46] Hellman, A. N., B. Vahidi, H. J. Kim, W. Mismar, O. Steward, N. L. Jeon and V. Venugopalan. Examination of axonal injury and regeneration in micropatterned neuronal culture using pulsed laser microbeam dissection. Lab on a Chip, 10(16):2083–2092, (2010). (PMCID: PMC3039457) [47] Hayakawa, C. K., E. O. Potma and V. Venugopalan. Electric field Monte Carlo simulations of focal field distributions produced by tightly focused laser beams in tissue. Biomedical Optics Express, 2(1):278– 290, (2011). (PMCID: PMC3039457) [48] Gardner, A. R. and V. Venugopalan. Accurate and efficient Monte Carlo solutions to the radiative transport equation in the spatial frequency domain. Optics Letters, 36(12):2269–2271, (2011) (PMCID: PMC3312025) [49] Martinelli, M., A. R. Gardner, D. J. Cuccia, C. K. Hayakawa, J. Spanier and V. Venugopalan. Analysis of single Monte Carlo methods for prediction of reflectance from turbid media. Optics Express, 19(20):19627–19642, (2011). [50] Ma, H., W. Mismar, Y. Wang, D. W. Small, M. Ras, N. L. Allbritton, C. E. Sims and V. Venugopalan. Impact of release dynamics of laser-irradiated polymer micropallets on the viability of selected adherent cells. Journal of the Royal Society Interface, 9(71):1156–1167, (2012). PMCID: In process. [52] Balu, M., A. Mazhar, C. K. Hayakawa, R. Mittal, T. B. Krasieva, K. König, V. Venugopalan and B. J. Tromberg. In Vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin. Biophysical Journal, 85(1):258–267, (2013). [53] Gardner, A. R., A. D. Kim and V. Venugopalan. Radiative transport produced by oblique illumination of turbid media with collimated beams. Physical Review E, 87(6):063308 (11 pages) (2013). [55] Compton, J. L., A. N. Hellman, and V. Venugopalan. Hydrodynamic determinants of cell necrosis and molecular delivery produced by pulsed laser microbeam irradiation of adherent cells. Biophysical Journal, 105(9):2221–2231, (2013). [56] Hayakawa, C. K., J. Spanier, and V. Venugopalan. A comparative analysis of discrete and continuous absorption weighting estimators used in Monte Carlo simulations of radiative transport in turbid media. Journal of the Optical Society of America A, 31(4):301–311, (2014).

D. Research Support Active Research Support DGE-1144901 (Venugopalan) 07/01/2012 – 06/30/2017 1.0 summer NSF $2,999,531 (Total Cost) IGERT: Biophotonics Across Energy Space and Time (BEST) The BEST IGERT is a training grant that provides graduate trainee support to participate in a new interdisciplinary model for graduate student education and training in Biophotonics than spans and includes graduate students in the biological sciences, physical sciences and engineering. The hands-on education and training program integrates physics, chemistry, engineering, and life-science principles across spatial and temporal scales. The interaction of, and collaboration between, biomedical science, physical science, and engineering students throughout the graduate traineeship will drive advances in Biophotonics technologies, computational methods, and molecular probes to solve important problems in bio-molecular, cellular, tissue, and whole organismal systems. Overlap: None Role: PI

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Active Research Support (continued) P41 EB 015890 (Tromberg) 04/01/2013 – 03/30/2018 1.0 summer NIH/NIBIB $6,258,510 (Total Cost) A Laser Microbeam Biotechnology Resource The Laser Microbeam and Medical Program (LAMMP) is a NIH Biomedical Technology Resource Center dedicated to the use of lasers and optics in biology and medicine. LAMMP provides (a) Virtual Photonics Technologies for the development of computational models and methods for simulating and visualizing light propagation in cell and tissues, (b) Microbeam and Microscopy Technologies for the development of highresolution non-linear optical microscopy techniques combined with laser microbeams for cellular manipulation, (c) Multimodality Endoscopic Technologies for in vivo imaging of tissue structure, composition, and physiology with high imaging speed, contrast, sensitivity, and spatial resolution in hollow organs, and (d) Diffuse Optical Technologies for the development of model-based methods utilizing multiply scattered light capable of quantitative subsurface metabolic spectroscopy and imaging across spatial scales. Overlap: None Role: co-PI K25 EB007309 Hayakawa (PI) 08/01/2008 – 07/31/2013 NIH/NIBIB A Virtual Tissue Simulator for Biomedical Optics This grant funds the development of a novel computational platform for the simulation of light transport in tissues using advanced Monte Carlo techniques. Trainee: Carole Hayakawa Role: Primary Mentor Completed Research Support in last three years R01 HG004843 (Allbritton, UNC Chapel Hill) 02/23/2009 – 01/31/2012 NIH/NHGRI Rapid Genetic Engineering of Stem Cells This grant funds the development of a single platform for the generation of gene-targeted cells to produce genetically modified animals. The platform will integrate microtechnologies consisting of microfabricated cell sorting arrays, miniaturized high-throughput DNA analysis techniques and microfluidic-based DNA separations. Overlap: None Role: co-PI, sub-contract to UC Irvine P41 RR01192-30S4 Tromberg (PI) 10/01/2009 – 03/31/2013 NIH/NCRR A Laser Microbeam Biotechnology Resource-Research Supplements to Promote Diversity in Health-Related Research This supplement to the main P41 grant shown above supports the graduate education of Jonathan Compton for his doctoral research on pulsed laser microbeam interactions with cells. Role: Primary Mentor P41 RR01192-30S2 Tromberg (PI) 09/01/2009 – 08/31/2011 NIH/NCRR Development of Medical Biophotonic Technologies for Imaging and Therapy This supplement to the main P41 grant shown above is aimed to accelerate the translational impact of LAMMP Virtual Photonics technologies developments for therapeutic photomedicine applications. Role: co-PI

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Completed Research Support in last three years (continued) GCP07-10255 Venugopalan (PI) 10/01/2008 – 1/31/2012 University of California Industry-University Cooperative Research Program Mechanisms of Molecular Delivery to Single Cells using Pulsed Laser Microbeams The overall goal of this research is to establish the mechanisms by which pulsed laser microbeam irradiation can efficient and reproducible delivery of biologically-relevant molecules (e.g., peptides, proteins, RNAs, plasmids) to single cells at high throughput. This mechanistic understanding will provide a basis to select optimal laser microbeam irradiation parameters for a given cellular/molecular system and facilitate the design of high-throughput systems aimed to provide efficient and reproducible laser-based cellular manipulation for research in the biosciences and applications in the pharmaceutical and biotechnology industries. P41 RR-01192 Tromberg (PI) 04/01/2008 – 03/31/2013 NIH/NCRR A Laser Microbeam Biotechnology Resource The Laser Microbeam and Medical Program (LAMMP) is a NIH Biomedical Technology Resource Center dedicated to the use of lasers and optics in biology and medicine. LAMMP provides Microbeam and Microscopy Technologies for optical manipulation and functional imaging of living cells and tissues, Medical Translational Technologies for monitoring, treating, and imaging pre-clinical animal models and humans, and Virtual Photonics Technologies for developing computational methods that advance the performance of biophotonic technologies, and enhance the information content derived from optical measurements. Role: Co-Principal Investigator R43RR025980 Weed/Venugopalan (PI’s) 05/01/2009 – 04/30/2011 NIH/NCRR Versatile system to select and expand individual or multiple adherent-type cells The objective of this Phase I SBIR effort is to make the laser microbeam/micropallet approach for the selection and expansion of adherent-type cells available for biomedical research and the pharmaceutical/biotechnology industries. We determine the optimal laser microbeam and optical parameters that achieve release of SU-8 and PMMA micropallets with maximum cell viability and recultivation efficiency. These studies will define the parameters necessary to design and build an easy-to-use optical platform to be integrated with standard biological microscopy instruments. Role: Academic PI; Kent Weed, LightWorks Optics Inc., Industrial PI

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