Work History

Work History
Jan 2008 - Present

Editor and Technical Advisor

FundScience.org

FundScience is a non-profit organization, the central goals of which are to educate the public regarding the scientific research that impacts their lives, and to give the public a direct mechanism to influence the funding of this research. As a Technical Advisor, I provide insight into research funding and mechanisms by which to institute funding, as well as areas of research that merit funding. In addition, I manage and contribute to the FundScience.org blog, where I write about science funding, interesting areas of research and life as a scientist.

Aug 2006 - Present

Postdoctoral Fellow

I am currently a Postdoctoral Fellow in the laboratory of Dr. Paul Robbins at the University of Pittsburgh School of Medicine. My Postdoctoral work has focused on developing and testing AAV as a vector for gene therapy of type-1 and type-2 diabetes. I have successfully utilized AAV vectors expressing therapeutic genes, including the immunomodulatory molecule IL-4 and the beta cell growth factors GLP-1 and HGF, to induce beta cell proliferation and reverse diabetes in mouse models of type-1 and type-2 diabetes. In addition, I am now using AAV vectors and retrovirus vectors for gene therapy of premature aging.

Aug 2001 - Jul 2006

Graduate Student

Wake Forest University School of Medicine

My graduate training was in the areas of molecular virology, virus-host interaction, cancer biology, and apoptosis. My graduate research involved defining the mechanism by which vesicular stomatitis virus (VSV) induces apoptosis. Specifically, I worked on a matrix (M) protein mutant VSV that is a promising candidate for oncolytic virus therapy. My work led to the discovery of a novel mechanism of virus-induced apoptosis. Briefly, apoptosis induced by the M protein mutant VSV is dependent upon new host gene expression, specifically expression of the dsRNA-dependent protein kinase PKR and the Fas/CD95 adaptor protein Daxx, and requires the activation of caspase-8. This mechanism of apoptosis requires signaling through the death receptor Fas/CD95, but not the Fas-associated death domain protein FADD. This indicates that Daxx is more important than FADD for apoptosis induced by this oncolytic virus, and is the first report of a requirement for Daxx in virus-induced apoptosis.

Oct 2000 - Jul 2001

Research Assistant

Ardent Pharmaceuticals, Inc. (now Enhance Biotech)

Student Research Assistant in the Department of Molecular Biology (supervisor: Vic Wei, Ph.D.). Primary responsibility was to conduct receptor binding assays to test binding efficiency of candidate compounds in mouse brain tissue. 

Education

Education
2001 - 2006

Ph.D.

Wake Forest University School of Medicine

My graduate training was in the areas of molecular virology, virus-host interaction, cancer biology, and apoptosis. My graduate research involved defining the mechanism by which vesicular stomatitis virus (VSV) induces apoptosis. Specifically, I worked on a matrix (M) protein mutant VSV that is a promising candidate for oncolytic virus therapy. My work led to the discovery of a novel mechanism of virus-induced apoptosis. Briefly, apoptosis induced by the M protein mutant VSV is dependent upon new host gene expression, specifically expression of the dsRNA-dependent protein kinase PKR and the Fas/CD95 adaptor protein Daxx, and requires the activation of caspase-8. This mechanism of apoptosis requires signaling through the death receptor Fas/CD95, but not the Fas-associated death domain protein FADD. This indicates that Daxx is more important than FADD for apoptosis induced by this oncolytic virus, and is the first report of a requirement for Daxx in virus-induced apoptosis.

1997 - 2001

B.S.

Magna Cum Laude

Skills

Skills

Animal models

  Small animal anatomy, handling, and experimentation; Type 1 and Type 2 diabetes models; tumor xenografts    

Sterile tissue culture work

with human and murine primary cells and transformed cells/cell lines 

Microscopy

includes laser-scanning confocal microscopy, live-cell imaging, time-lapse microscopy  

Immunology techniques

include flow cytometry, ELISA, ELISPOT, intracellular cytokine staining, operation of BD FACSCaliberTM and BDTM LSR II cytometers, as well as CellQuest Pro and FACSDiva analysis software  

Molecular biology techniques

include Western blotting, PCR, quantitative RT-PCR, microarrays, cloning techniques, plasmid preparation and purification, stable and transient transfection of cell cultures with plasmid DNA or siRNA

Virology techniques

include preparation and propagation of adeno-associated virus, adenovirus, lentiviruses, and vesicular stomatitis virus; virus titration via plaque assay and dot blot genomic DNA analysis

Summary

Molecular biologist with a broad, multidisciplinary skillset, working in the area of Gene Therapy for autoimmune diseases. Currently seeking a career in the biotechnology/pharmaceutical industry that allows me opportunities to utilize and build upon my expertise in molecular biology, cell biology, virology and immunology for the design and development of therapies for human diseases.

Publications

Research Articles

1)Gaddy, D.F., M.J. Riedel, T.J. Kieffer, and P.D. Robbins. (in preparation) In vivo expression of HGF/NK1 and GLP1 from dsAAV vectors enhances pancreatic beta cell proliferation and improves pathology of Type-2 diabetes.

2)Gaddy, D.F., M.J. Riedel, S. Pejawar-Gaddy, T.J. Kieffer, and P.D. Robbins. (in preparation) Beta cell-specific expression of IL-4 and GLP-1 improves pathology of Type-1 diabetes.

3)Gaddy, D.F., Z.W. Whitlow, M.O. McKenzie and D.S. Lyles. (in preparation) P protein contributes to the induction of apoptosis by wild-type vesicular stomatitis virus.

4)   Pejawar-Gaddy, S., Y. Rajawat,, J. Xue., D.F. Gaddy, O.J. Finn, R.P. Viscidi, and I. Bossis. (submitted) Generation of a tumor vaccine candidate based on conjugation of a MUC1 peptide to polyionic papillomavirus VLPs

5)Riedel, M.J., D.F. Gaddy, A. Asaidi, P.D. Robbins, and T.J. Kieffer. (submitted) DsAAV8-Mediated Expression of GLP-1 in Pancreatic Beta-Cells Prevents Streptozotocin-Induced Diabetes.

6)Gaddy, D.F. and D.S. Lyles. 2007. Oncolytic vesicular stomatitis virus induces apoptosis via a novel mechanism that is dependent on signaling through PKR, Fas, and Daxx. J Virol. 81(6): 2792-2804.

7)Gaddy, D.F. and D.S. Lyles. 2005. Vesicular stomatitis viruses expressing wild-type or mutant M proteins activate apoptosis through distinct pathways. J Virol. 79(7): 4170-4179.

Review Articles

1)Gaddy, D.F. and P.D. Robbins. (submitted, invited review) Approaches for musculoskeletal gene therapy: an overview.

2)Gaddy, D.F. and P.D. Robbins. 2008. Current status of gene therapy for rheumatoid arthritis. Curr Rheumatol Rep. 10(5): 398-404.

Book Chapters

1)Gaddy, D.F., M.A. Ruffner, and P.D. Robbins. (in press) Autoimmune disorders. A Guide to Human Gene Therapy. New Jersey: World Scientific.

Abstracts

2008“DsAAV8-mediated expression of GLP-1 in pancreatic beta-cells prevents streptozotocin-induced diabetes.” Oral presentation. Annual Meeting of the Canadian Diabetes Association, Montreal, QC.

2008“DsAAV8-mediated expression of IL-4 and b cell growth factors modulates diabetes in NOD mice.” Oral presentation. 11th Annual Meeting of the American Society of Gene Therapy, Boston, MA.

2007“Comparison of rAAV serotypes for therapeutic gene transfer to islets for abrogation of autoimmunity in diabetes.” Oral presentation. 10th Annual Meeting of the American Society of Gene Therapy, Seattle, WA.

2006“Oncolytic vesicular stomatitis virus induces apoptosis via signaling through PKR, Fas and Daxx.” Poster presentation. 9th Annual Meeting of the American Society of Gene Therapy, Baltimore, MD.

2005“Analysis of host gene products that contribute to the induction of apoptosis by vesicular stomatitis virus.” Oral presentation. 24th Annual Meeting of the American Society for Virology, State College, PA.

2004“Analysis of host gene products that contribute to the induction of apoptosis by vesicular stomatitis virus.” Oral presentation. 23rd Annual Meeting of the American Society for Virology, Montreal, QC.

2004“Analysis of host gene products that contribute to the induction of apoptosis by vesicular stomatitis virus.” Oral presentation. 8th Southeastern Regional Virology Conference, Atlanta, GA.

2000“Can phosphatase inhibitors be used to enhance apoptosis induced by chemotherapeutic agents?” Poster presentation. NCSU Undergraduate Research Symposium, Raleigh, NC.

Honors and Awards

2007-Present:Juvenile Diabetes Research Foundation Postdoctoral Fellowship

2007:Travel Award, 10th Annual Meeting of the American Society of Gene Therapy

2005:Travel Award, 24th Annual Meeting of the American Society for Virology

2003-2005:WFU Dept. of Microbiology and Immunology Ruth L. Kirschstein National Research Service Award

1998-Present:Golden Key National Honor Society

1998-1999:Gamma Sigma Delta Sophomore Scholarship

Current Research Support

09/1/2007-Present

3-2007-728 (Gaddy, PI)

Juvenile Diabetes Research Foundation

A Gene Therapy-based Approach for Abrogation of Autoimmunity in Diabetes

Role: Postdoctoral Fellow

Goal: To enhance local delivery specifically to pancreatic b cells in mouse and non-human primate models of Type 1 Diabetes (T1D). Furthermore, experiments proposed in this grant will utilize rAAV vectors for the delivery of therapeutic transgenes encoding GLP-1 and HGF. These proteins have been shown to have a variety of anti-diabetic properties, including the promotion of b cell growth and insulin secretion. Therefore, delivery of these genes to bcells via rAAV vectors has the potential to prevent T1D progression when administered early. Moreover, rAAV delivery of these therapeutic genes, in combination with immunomodulatory therapy, has the potential to promote regression of T1D when administered after T1D onset by promoting b cell regeneration. The successful completion of the proposed studies should result in the development of rAAV-based therapies for T1D.

Major areas of expertise

Molecular biology, cell biology, virology, gene therapy, virus vectors, autoimmunity, oncolytic viruses, host-pathogen interactions, small animal models

Professional Memberships

American Association for the Advancement of Science

American Society of Gene and Cell Therapy

American Society for Microbiology

American Society for Virology