Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Research Accomplishments: I participated in the development of the use of Surface Enhanced Raman Spectroscopy nanoparticles for the detection of signaling events in single cancer cell. Raman Spectroscopy relies on inelastic scattering, or Raman scattering. Spontaneous Raman scattering is typically very weak. However, the Composite Organic-Inorganic Nanoparticles (COINs) used by us have enhanced Raman spectra. Each particle has a different Raman tag generating a unique fingerprint Raman spectra. This approach has tremendous advantages over the commonly used fluorescence tags. Fluorescence has broad overlapping spectra making the use of multiple tags simultaneously difficult. On the other hand, COINs have narrow peak spectra and therefore are more useful for multiple tag use theoretically we can do 100 such measurements. We had technical know how to use 9 COINs simultaneously for cell signaling measurements in cancer cells. Intel, Santa Clara transferred technology to Stanford for Immunoassay and biological applications. I used these COINs for studying signaling networks in live and dead cells. We also used them for drug delivery into lung cancer cells.I Applied for patent at Stanford University entitled “Determination of DNA copy number by Flow cytometry”. I showed for the first time that the oxidative stress leads to hepatocellular carcinoma in mouse models. Previously, only oncogenes over expression models were employed to characterize liver tumors. I showed that knocking a gene from oxidative pathway (Copper Zinc Superoxide dismutase) lead to hepatocellular carcinoma. This paper was well received and has 141 citations till today. I later discovered biomarkers for tumor progression by employing proteomic approach. At Sankara Netralaya graduate student Ms Kalmodia fabricated gold nanoparticles with SERS signature using green nanotechnology under my supervision. We are applying for Patent) Summary of qualification Molecular Biologist working at the intersection of technology and traditional laboratory research in different departments at Stanford University Expertise in developing, implementing and managing multidisciplinary projects Extensive experience with both cellular assays and DNA and protein techniques including gene expression, 2D gels and mass spectrometry, Northern and Southern blotting, Flow Cytometry, HPLC, antibody detection, immunohistochemistry and conjugation to fluorophores and nanoparticles, RTPCR, cloning, library screens, sequencing, electrophoresis, fluorescence, EPR and Raman spectroscopy. Experience with mouse models for understanding tumor progression and neurodegeneration (Sod1-/-, Myc overexpression under the control of TET promoter, Sod2-/-) human tissue, blood samples and tumor cell lines. Strong problem solving and organizational skills Excellent oral and written communication skills Fabrication of composite organic and inorganic nanoparticles. Strong writing skills with 27 published papers in peer reviewed journals Has funded grants as principal investigator and co-principal investigator. Supervised grad students and post doctoral students. Interacted with Stanford Nanotechnology Centre CCNE(centre for cancer Nanotechnology Therapy Response) http://mips.stanford.edu/grants/ccne/ http://mips.stanford.edu/grants/ccne/postdocs.html PROFESSIONAL EXPERIENCE Scientist Sankaranetralaya, Chennai-2011 (Accepted grants as Investigator). Fabrication of Mdm2 peptide conjugated Gold Nanoparticles for targeted therapy of Retinoblastoma (Co-PI) Aptamer-Based Radiopharmaceuticals for Diagnostic Imaging and Targeted Radiotherapy of Epithelial Cancers (Co-PI) Proteomics and Phosphoproteomics by Mass spectrometry and Flow cytometry in Retinoblastoma. (Bioinformatic collaborator Dr Debashis Shaoo is from Stanford University. Dr Akhilesh Pandey and Dr Harsha from Institute of Bioinformatics) (PI) Centre for excellence and innovations in Biotechnology “Retinoblastoma Research-Therapeutics” Team leader Dr Krishna Kumar. Co-Team leader along with Dr Narayanan. 2005-2009 Research Scientist Department of Microbiology and Immunology, Baxters Labs for Genetic Pharmacology, Stanford University Palo Alto CA http://www.stanford.edu/group/nolan/members/members.html Collaborated with Intel Corporation having 20 member team on it for developing cell assay for biomarker discovery using nanoparticles and Raman Spectroscopy in comparison with Flow Cytometry data. Developed methodology for live cell signaling in Lung cancer cell lines using nanoparticles Performed nanoparticle drug delivery for curing tumors in mouse models. Developed new flow cytometry techniques for single cell determination of gene expression and gene copy number using FACS. Contributed to identifying threshold of MYC expression using TET system leading to disease formation in lymphoma cells and lymphoma tissues using proteomics (2D gels and mass spectrometry), DNA arrays, quantitative PCR, Western blotting. Employed mouse models of lung, human tumor samples and lung cancer cell lines to detect alteration in pathways and signaling under disease conditions using proteomics, spectrometry, quantitative PCR and Flow Cytometry. Provided rigorous trouble shooting and fine tuning of the assay to produce the best method for sensitive and reproducible detection. 2000-2004Postdoctoral Fellow. Dept. of Neurology & Neuroscience - Stanford University, Palo Alto CA (2002 – 2004) Dept. of Pediatrics – San Francisco University San Francisco, CA (2000 – 2002) Successfully identified of pathways leading to hepatocarcinogenesis and neurodegeneration in CuZn superoxide dismutase (SOD) and MnSOD, CuZnSOD knockout mice using proteomics, quantitative PCR, western blots and immuno-histochemistry. Identified cancer biomarkers associated with tumor progression. Identified the genetic modifiers affecting the lifespan of Sod2/- mice using 250 whole genomic mouse MIT markers to do quantitative loci determination by 6 generations of back cross. Showed in Ts65 mice, partial extra chromosome16 not only caused Down syndrome but also increased oxidative stress. Using biochemical assays and QPCR identified that low density grown neural stem cells had oxidative stress compared to high density grown cells. PUBLICATIONS: 1. Kode K, Shachaf CM, Elchuri SV, Garry Nolan, David S. Paik Raman Labeled Nanoparticles for In-vivo Imaging: Characterization of Variability and Improved Method for Unmixing (J of Raman Spectroscopy) (2012) (accepted). 2. Subramaniyan N, Raghunathan V , Kanwar JR, Kanwar RK, Elchuri SV, Khetan V, Subramanian K. Target specific delivery of Doxorubicin to Retinoblastoma using EpCAM Aptamer (2012) Molecular Vision 2012;18:2783-95 3. Shachaf CM, Elchuri SV, Koh AL, Zhu J, Nguyen LN, Mitchell DJ, Zhang J, Swartz KB, Sun L, Chan S, Sinclair R, Nolan GP. A novel method for detection of phosphorylation in single cells by surface enhanced Raman scattering (SERS) using composite organic-inorganic nanoparticles (COINs). PLoS One. b2009;4(4):e5206. Times Cited: 5 . This work is high lighted in Bioanalysis Journal Title: Nanoparticle 'fingerprinting' technique could improve cancer diagnosis Author(s): [Anon]Source: BIOANALYSIS Volume: 1 Issue: 2 Pages: 270-270 Published: MAY 2009 4. Koh AL, Shachaf CM, Elchuri S, Nolan GP, Sinclair R. Electron microscopy localization and characterization of functionalized composite organic-inorganic SERS nanoparticles on leukemia cells. Ultramicroscopy. 2008 Dec;109(1):111-21. Times Cited: 8 5. Shachaf CM, Gentles AJ, Elchuri S, Sahoo D, Soen Y, Sharpe O, Perez OD, Chang M, Mitchel D, Robinson WH, Dill D, Nolan GP, Plevritis SK, Felsher DW. Genomic and proteomic analysis reveals a threshold level of MYC required for tumor maintenance. Cancer Res. 2008 Jul 1;68(13):5132-42. (Second author). Times Cited: 21 (Article selected by Faculty as 1000 best papers of the year) 6. Shachaf CM, Perez OD, Youssef S, Fan AC, Elchuri S, Goldstein MJ, Shirer AE, Sharpe O, Chen J, Mitchell DJ, Chang M, Nolan GP, Steinman L, Felsher DW. Inhibition of HMGcoA reductase by atorvastatin prevents and reverses MYC-induced lymphomagenesis. Blood. 2007 Oct 1;110(7):2674-84. Times Cited: 18 7. Elchuri S, Naeemuddin M, Sharpe O, Robinson WH, Huang TT. Identification of biomarkers associated with the development of hepatocellular carcinoma in CuZn superoxide dismutase deficient mice. Proteomics. 2007 Jun;7(12):2121-9. Times Cited: 10 8. Erker L, Schubert R, Elchuri S, Huang TT, Tarin D, Mueller K, Zielen S, Epstein CJ, Wynshaw-Boris A. Effect of the reduction of superoxide dismutase 1 and 2 or treatment with alpha-tocopherol on tumorigenesis in Atm-deficient mice. Free Radic Biol Med. 2006 Aug 15;41(4):590-600. Times Cited: 10 9. Huang TT, Naeemuddin M, Elchuri S, Yamaguchi M, Kozy HM, Carlson EJ, Epstein CJ. Genetic modifiers of the phenotype of mice deficient in mitochondrialsuperoxide dismutase. Hum Mol Genet. 2006 Apr 1;15(7):1187-94. Epub 2006 Feb 23. Times Cited: 32 10. Lynn S, Huang EJ, Elchuri S, Naeemuddin M, Nishinaka Y, Yodoi J, Ferriero DM, Epstein CJ, Huang TT. Selective neuronal vulnerability and inadequate stress response in superoxide dismutase mutant mice. Free Radic Biol Med. 2005 Mar15;38(6):817-28. Times Cited: 14 11. Elchuri S, Oberley TD, Qi W, Eisenstein RS, Jackson Roberts L, Van Remmen H, Epstein CJ, Huang TT. CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene. 2005 Jan13;24(3):367-80. Times Cited: 141 12. Limoli CL, Rola R, Giedzinski E, Mantha S, Huang TT, Fike JR. Cell-density-dependent regulation of neural precursor cell function. Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):16052-7. Times sited 57 13. Huang TT., Mantha S., Epstein C.J. (2004) The role of oxidative damage in the pathogenesis of Down syndrome. In Redox-Genome Interactions in Health and Disease, Eds, J. Fuchs, M. Podda, L. Packer as the Oxidative Stress and Disease series (Eds L. Packer and E. Cadenas). Marcel Dekker, Inc. New York, Basel. pp 409-424 14. Huang TT, Carlson EJ, Kozy HM, Mantha S, Goodman SI, Ursell PC, Epstein CJ.Genetic modification of prenatal lethality and dilated cardiomyopathy in Mn superoxide dismutase mutant mice. Free Radic Biol Med. 2001 Nov 1;31(9):1101-10. Times Cited: 45 ABSRTACTS 1. Kode K, Shachaf C, Elchuri S, Nolan G, Paik DS. "Parametric Modeling of Raman Spectra of Nanoparticles for Quantitative Unmixing." accepted to World Molecular Imaging Congress (WMIC), Montreal, Canada, September 2009. http://www.wmicmeeting.org/abstracts/data/papers/0705.html 2. Kode K, Elchuri S, Shachaf C, Paik D. "Parametric Modeling of Raman Spectra of Nanoparticles for Quantitative Unmixing.", 9th Symposium, Biomedical Computation at Stanford, October 2008. 3. Shachaf CM, Elchuri S, Zhu J, Nguyen, Zhang J, Sun L, Chang S, and Nolan GP. Detection of surface molecules and phosphorylation events by surface enhanced raman scattering (SERS) using composite organicinorganic nanoparticles (COINs) in single cells. AACR Meeting Abstracts, Apr 2008; 2008: 4742. 4. Shachaf C, Gentles A, Elchuri S, Sahoo D, Chang M, Sharpe O, Nolan GP, Plevritis S, and Felsher D. Genomic and proteomic analysis reveals a threshold level of MYC required for tumor maintenance. AACR Meeting Abstracts, Apr 2008; 2008: 91 AiLeen K, Shachaf CM, Elchuri S, Nolan GP, Sinclair R Electron microscopy characterization of composite organic inorganic nanoparticles (COINs) for extra cellular analyses. Microscopy and Microanalyses meeting 2008 5. Shachaf CM, Perez OD, Youssef S, Chang M, Elchuri S, Goldstein MJ, Nolan GP, Steinman L and Felsher DW. American Society of Cell Biology. 2005 Annual meeting. 6. Shachaf C, Perez O, Elchuri S, Mitchell D, Felsher D, and Nolan GP. Targeting HMGcoA reductase for prevention of MYC expressing lymphoma. AACR Meeting Abstracts, Oct 2007; 2007: C181. 7. Clement, MH,Chandra S, Mantha S, Huang TT, Valentine JS, Gralla EB “ EPR iron homeostasis studies in organisms lacking Cu/Zn superoxide dismutase” retreat in Chemistry biology interface organized by Chemistry and Biochemistry Department of University of California at Los Angels (2003). 8. Elchuri S, Oberley TD, Van Remmen H, Epstein, CJ, and Huang TT, “Increased oxidative stress leads to the development of hepatocellular carcinoma in CuZnSOD mutant mice,” 43rd Annual Meeting, American Society for Cell Biology, San Francisco, CA, 2003. 9. Mantha SV, Oberley, TD, Van Remmen H, Epstein, CJ and Huang T-T, “Increased oxidative stress and dysregulation of cell cycle proteins in CuZnSOD deficient mice,” selected for oral presentation, 9th annual meeting, The Oxygen Society, San Antonio, TX, Nov 2002. 10. Mantha S, Oberley TD, Epstein CJ, Huang T-T, “Hepatocellular carcinoma and altered aconitase activities in CuZn superoxide dismutase deficient mice,” Free Radical Biology and Medicine 31: 288, Suppl, 2001. 12 published papers in Plant Sciences will be provided on request. Accepted 15) Sushma Kalmodia , Jaidev Rajeswari.R , Wenrong Yang , Colin J. Barrow2S. Ramaprabhu, Subramanian Krishnakumar , Sailaja Elchuri. Synthesis of SERS active Gold Nano particles. International Journal of Nanomedicine (accepted) 16) Targeted Expression of Suicide Gene by Tissue-specific Promoter and microRNA Regulation for Cancer Gene Therapy. Ravikanth Danda, Gopinath Krishnan , Khetan V, Sailaja Elchuri Nivedita Chatterjee, Krishnakumar S. (PLOS one accepted) Under Submission: Elchuri VS, KimS, Zare R, Nolan GP Shachaf CM: DNA copy number detection by Flow cytometry. (Nature Methods) Elchuri SV, Shachaf CM, Tabackman S, Dai H, Nolan GP. Dynamic cellular signaling in lung cancer using COIN nanoparticles. (Nano Letters) Elchuri SV, Shachaf CM, Nolan GP. Novel biomarkers in lung cancer signaling using COIN nanoparticles. ACS Nano) Web releases: New imaging tool could improve cancer diagnosis Nanoparticles use Raman tags to highlight features within cells Collaborations: Ongoing Research Projects Sl No. Title of Project Funding Agency Amount Fabrication of Mdm2 DST No SR/NM/NSpeptide conjugated Gold 83/2010 Nanoparticles for targeted therapy of Retinoblastoma 45,35,200 No. 2010/ Aptamer-Based 35/19/BRNS Radiopharmaceuticals for Diagnostic Imaging and Targeted Radiotherapy of Epithelial Cancers 45,00,000 Proteomics and Phospho- BT/01/CEIB/11/V/16 proteomics by Mass spectrometry in Retinoblastoma 1,20,00,000 Engineer a aptamer-siRNA chimeric conjugates for targeting epithelial cancers" Date of sanction and Duration 22nd july 20112014 July, 2011 for 3 years 2012 for 4yrs 3yrs Funds released 30 lakhs for one year (consumables and equipment payment for 2 SRFS