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Post doctoral associate Resume

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Post doctoral associate

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Objective:

I am an experienced Molecular Biologist with a strong research background in Gene Expression, Molecular Virology and Gene Therapy. My objective is to secure a research scientist position to investigate human diseases and devise innovative therapeutic approaches to treat them.

I have trained with Dr. Joseph Glorioso at the University of Pittsburgh School of Medicine. Our laboratory is at the forefront of efforts to engineer viral vectors for gene therapy of brain tumors, neurological disorders, pain, and for systemic delivery from peripheral sensory nerves. I have developed (i) technical expertise with a wide range of recombinant DNA techniques, (ii) extensive knowledge of virology and genetic engineering of recombinant viruses, (iii) a firm understanding of gene expression and its assessment.

To put my research pursuits in context, one of the major obstacles to gene therapy in the nervous system has long been the inability to achieve sustained therapeutic gene expression owing to silencing of various promoters in Herpes vectors. The only promoter that can escape this generalized silencing is the virus¡¦ own Latency Associated Promoter (LAP). To capitalize on the natural ability of this region to support sustained gene expression and boost the level of expression for gene therapy, I sought to understand the transcriptional regulation of this promoter.

During my postdoctoral studies, I addressed the neuronal basis of LAP promoter regulation using Transfac® and GenBank sequence alignment to identify putative neuronal-specific elements, and created site-directed and large deletion viruses via marker rescue recombination to determine their function in transcription activity. By multimerizing or improving the sequence homology with these neuronal-specific elements, we are now in a position to boost the level of gene expression from this naturally occurring, long-term Herpes promoter so as to achieve both sustained and significant levels of therapeutic gene expression.

Between 2002-2003, I was a member of a select team that conducted pre-clinical studies for the start-up gene therapy company Nurel Therapeutics Inc. We were responsible for verifying the safety and efficacy of the cutting edge, multi-gene recombinant Herpes viral vectors we had developed for multimodal treatment of brain-localized gliosarcomas and successfully filed an IND with the FDA in 2003. I gained valuable insights into the complex issues involved in the development of new therapeutics.

I would appreciate an opportunity to discuss the potential contribution I could make to advance the research efforts of your organization. I am confident that my scientific training, broad range of skills, and personal attributes such as scientific integrity, team spirit, and perseverance would make me a valued addition to your research team.

I look forward to hearing from you at your earliest convenience. Thank you for your consideration.

Sincerely

Karina Soares, Ph.D

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ence in Microbiology, First Class, Bombay University, 1989. Thesis Advisor: Dr. M. A. Khatkhatay, Professor and Head of the Microbiology Department, Sophia College, Bombay University, Bombay, India.
Dissertation Topic: Isolation and Characterization of a xylanase producer from soil.

Bachelor of Science in Microbiology, First Class, Bombay University, 1987. Department of Microbiology, Sophia College, Bombay University, Bombay, India.

APPOINTMENTS :-

1997-2003 Post-doctoral Research Fellow, University of Pittsburgh School of Medicine.

2002-2003 Served on a team of five scientists and neuro-oncologists engaged in preclinical research for the start-up gene therapy company Nurel Therapeutic Inc., co-founded by Principal Investigators at the University of Pittsburgh School of Medicine. This work led to the successful filing of an Investigational New Drug (IND) application with the FDA for the development of multi-gene recombinant Herpes virus vectors for cancer (multi-modal treatment for gliosarcoma brain tumors) in 2003.

TECHNICAL SKILLS :-

Recombinant DNA technology :- cloning, site-directed mutagenesis, transfection of adherent eucaryotic cell lines, transient expression studies using chloramphenicol transferase, beta-galactosidase and luciferase assays, preparation of transcriptionally active HeLa nuclear extracts, in vitro transcription-primer extension assays, electrophoretic mobility shift assays, DNAse I footprinting, DNA sequencing, northern blots, Southern blots, slot blots, DNA PCR and RT-PCR, yeast one-hybrid technology

Cell culture :- monolayers of Vero, CV-1, NIH3T3, neuronal cell lines (B103, PC12, Neuro2A, IMR-32), suspension cultures of S3 Hela cells in fermenter type stirrer flasks scaling them up from 100 ml volumes to 10 liter volumes to prepare transcriptionally active nuclear extracts for in vitro transcription, isolation and culture of primary sensory neurons from time pregnant rats (day E16 rat embryos), murine stem cells.

Virology :- generation of site-directed mutant, deletion and recombinant Herpes viruses and their rescuants, plaque assays, preparation of viral stocks

Animal studies :- corneal scarification, dissection of mice, stereotactic injection of rat brain

Microbiology :- isolation and purification of different xylanase-producing microrganisms from their natural habitats, comparison of the relative levels of xylanase produced using a substrate utilization agar plate assay, microbiological identification of the best xylanase producing organism, enzyme kinetic studies of xylanase, industrial application of the xylanase producer in simplifying complex plant substrates as carbon sources for growth of industrially important micro-organisms on a large scale

Computer skills :- familiarity with Oligo4.0, Genbank sequence searches and alignments using BLAST, Transfac database searching, DNA strider, PubMed, Medline, Medscape, OVID, ImageQuant optical quantitation program for measuring optical density of autoradiographic scans

PUBLICATIONS :-

Soares, K., D-Y. Hwang, R. Ramakrishnan, M. C. Schmidt, D. J. Fink and J. C. Glorioso. Cis-acting elements involved in transcriptional regulation of the Herpes simplex virus type 1 latency-associated promoter 1 (LAP1) in vitro and in vivo. 1996. Journal of Virology 70: 5384-5394.

Soares, M. K., W. H. Goins, J. C. Glorioso and D. J. Fink. Gene transfer to the nervous system using HSV vectors. 1998. In Gene Therapy and Molecular Biology. Boulikas T. (Ed.) Lychnia press, Athens, Greece Vol 1. pp. 215-229.

Laquerre, S., W. F. Goins, S. Moriuchi, T. J. Oligino, D. M. Krisky, P. Marconi, M. K. Soares, J. B. Cohen, D. J. Fink and J. C. Glorioso. Gene transfer tool: Herpes simplex virus vectors. 1999. In The Development of Human Gene Therapy. Friedman T. (Ed.). Cold Spring Harbor Laboratory press, pp 1-35.

Soares, M. K., W. F. Goins, J. C. Glorioso, and D. J. Fink. Advances in engineering HSV vectors for gene transfer to the nervous system. 1999. In Gene Therapy Technologies and Regulations: From Laboratory to Clinic. Meager A. (Ed.). John Wiley & Sons, Inc., Gene Therapy Technologies, pp 127-163.

Niranjan*, A., D. Wolfe*, M. Tamura, M. K. Soares, D. M. Krisky, L. D. Lunsford, S. Li, W. Fellows-Mayle, N. A. DeLuca, J. B. Cohen, and J. C. Glorioso. Treatment of Rat Gliosarcoma Brain Tumors by HSV-Based Multi-Gene Therapy Combined with Radiosurgery. 2003. Molecular Therapy 8: 530-542. (* co-first authors)

Soares, K., M. R. Alvira, D. J. Fink and J. C. Glorioso. Investigation into the neuronal-specificity of the latency-associated promoter of Herpes simplex virus type 1. Manuscript in preparation.

SCIENTIFIC PRESENTATIONS :-

Niranjan, A., D. P. Wolfe, M. Tamura, M. K. Soares, D. Krisky, D. L. Lunsford, D. Kondziolka, W. Fellows, N. DeLuca, J. Cohen, and J. C. Glorioso. Enhanced HSV-Based Suicide Gene Therapy for Rat Gliosarcoma Brain Tumors by Co-Delivery of TNFa, HSV TK, and Connexin 43 in Combination with Ganciclovir and Gamma knife Radiosurgery. Molecular Therapy 7(5):S281. Abstract #728, American Society of Gene Therapy meeting, Washington D.C. 2003.

D. P. Wolfe, A. Niranjan, M. Tamura, D. Krisky, M. K. Soares, L. D. Lunsford, D. Kondziolka, W. Fellows, N. DeLuca, and J. C. Glorioso. Multimodal Gene Therapy for Glioma; Gamma Knife Radiosurgery, Intratumoral Co-expression of Connexin43, Human TNFa, and HSV tk Suicide Gene Therapy in 9L Gliosarcoma Bearing Rats. University of Pittsburgh Annual Dean¡¦s Science Fair, 2002.

D. P. Wolfe, A. Niranjan, M. Tamura, D. Krisky, M. K. Soares, L. D. Lunsford, D. Kondziolka, W. Fellows, N. DeLuca, and J. C. Glorioso. Multimodal Gene Therapy for Glioma; Gamma Knife Radiosurgery, Intratumoral Co-expression of Connexin43, Human TNFƒÑ, and HSV tk Suicide Gene Therapy in 9L Gliosarcoma Bearing Rats. University of Pittsburgh School of Medicine, Department of Molecular Genetics and Biochemistry Annual Scientific Retreat, 2002.

S. Huang, W. F Goins, D. P. Wolfe, M. K. Soares, D. J. Fink and J. C. Glorioso. High-Level, Long-Term Transgene Expression from Chimeric LAP-HCMV Promoters in Neuronal Cells. 25th International Herpesvirus Workshop, Portland, OR. 2000.

S. Huang, W. F. Goins, D. Wolfe, K. Soares, D. J. Fink and J. C. Glorioso. Chimeric LAP-HCMV Promoters Support High-Level, Long-Term Transgene Expression in Neuronal Cells in Vitro. American Society of Gene Therapy meeting, Denver CO. 2000.

K. Soares and J. C. Glorioso. Cis-Acting Elements Involved in Transcriptional Regulation of the Herpes Simplex Virus Type-1 Latency Associated Promoter 1 (LAP1). 21st International Herpesvirus Workshop, Northern Illinois University, DeKalb, IL. 1996.

K. Soares, D-Y Hwang, R. Ramakrishnan, M. C. Schmidt, D. J. Fink and J. C. Glorioso. Cis-acting Elements Involved in Transcriptional Regulation of the Herpes Simplex Virus Type-1 Latency-Associated Promoter 1 (LAP1). TIGR Science Foundation Inc., Genomic science series, Conference on Gene therapy. Hilton Head, South Carolina. 1996.

K. Soares, D-Y. Hwang, D. J. Fink, M. C. Schmidt and J. C. Glorioso. Transcriptional Regulation of the Latency Associated Promoter (LAP1) of Herpes Simplex Virus Type-1. UNESCO sponsored conference on Gene Therapy. New Delhi, India. 1995.

M. K. Soares, D-Y. Hwang, D. J. Fink, M. C. Schmidt and J. C. Glorioso. Cis-trans Interactions Involved in Transcriptional Regulation of the Latency Active Promoter (LAP1) of HSV-1. The 19th International Herpesvirus Workshop, University of British Columbia, Vancouver, Canada. 1994.

M. A. Bender, P. Marconi, K. Soares, K. Vrana, S. Triezenberg, T. Sherman, M. Zigmond, D. Fink and J. C. Glorioso. HSV-1 Gene Transfer and Expression of a Functional Transcriptional Activation (Gal4:VP16) in the Brain. Society for Neuroscience Annual Meeting, Washington D. C. 1994.

D-Y. Hwang, S. W. French, M. K. Soares and J. C. Glorioso. Identification of Cis-acting elements within the TATA-box containing Latency Active Promoter of Herpes simplex virus type-1. XV111 International Herpesvirus Workshop, Pittsburgh, PA. 1993.

ACADEMIC HONORS :-

Best Teaching Assistant, Medical Microbiology laboratory, University of Pittsburgh School of Medicine, 1991.
The Bombay Port Trust Educational Scholarship 1982-1987, 1987-1989.
Bombay Port Trust Merit Prizes 1982, 1987, 1989.
Aldona Association Merit Prizes 1982, 1987, 1989.

TEACHING EXPERIENCE :-

1991-1994. Teaching Assistant, Medical Microbiology Laboratory for Medical students, University of Pittsburgh School of Medicine.

1992-1994. Student facilitator, Problem Based Learning sessions for Medical students, University of Pittsburgh School of Medicine.

MEMBERSHIP IN PROFESSIONAL SOCIETIES :-

Associate member, Pittsburgh Committee for Virology till 2003
Associate member, American Society for Gene Therapy till 2003

REFERENCES :-

Joseph C. Glorioso, PhD. Professor and Chairman, Department of Molecular Biology and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA. Phone: (412) 648-8105. E-mail: glorioso+@pitt.edu

Neal A. Deluca, PhD. Professor, Department of Molecular Biology and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA. Phone: (412) 648-8770. E-mail: ndeluca@pitt.edu

Sidney M. Morris, PhD. Professor, Department of Molecular Biology and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA. Phone: (412) 648-9338. E-mail: smorris@pitt.edu

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