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Transcript
CURRICULUM VITAE
Name:
DEBORAH JULIE PHIPPARD
Nationality:
British with permanent US resident status
Education:
Ph.D. University of London (1991-1994)
Molecular & Cell Biology, Developmental Biology & Genetics
Thesis title: Homeobox gene expression during mouse mammary
gland development
BSc. (Hons). South Bank University, London (1983-1987)
Biotechnology & Industrial Biology
Research Experience:
2009- Present
Executive Director, Biomarker & Discovery Research, Immune Tolerance Network.
Responsible for running a department comprised of 35 scientists, biostatisticians,
programmers/data managers and operations experts, with myriad external contracts
dedicated to leading mechanistic research for each of the clinical trials of the ITN.
The ITN is a NIH-funded initiative to facilitate the advancement of immune
tolerance-inducing procedures in human clinical practice, towards the development of
new and improved treatment and monitoring protocols in kidney, liver and islet
transplantation, autoimmune, asthma & allergic diseases.
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Responsible for designing and implementing a comprehensive mechanistic assay
and statistical analysis plan for every ITN clinical trial.
Identifies and manages a network of core laboratories in industry (contract
research organizations) and academia which run all ITN mechanistic assays.
Includes ensuring technical excellence, tracking productivity, setting and
managing budgets.
Manages the team responsible for building, maintaining and running the databases
that receive, clean and house all the ITN mechanistic data.
Manages a team of biostatisticians that analyze all ITN mechanistic data in
conjunction with clinical information.
Responsible for building and implementing a web portal with the architecture
behind it to merge clinical and mechanistic data in real time and allow interactive
querying, sorting and graphing as well as more complex visualization tools. This
is a large collaborative project with multiple 3rd party vendors. Deborah’s team is
responsible for the overall design, identification of appropriate vendors, timeline
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and implementation of this project. Vendor contracts were estimated to be $9.8
million over 4 years
Liases with Trial Principal Investigators to interpret clinical/mechanistic data and
present it to the scientific community including the ITN Network Steering
Committee
2005- 2009
Group Leader, Inflammation Discovery, Roche Palo Alto, LLC.
Responsible for leading a group of 5 scientists accountable for Pharmacodynamic
(PD) Biomarker Discovery and Novel Drug Discovery.
1. PD Biomarker Discovery to support multiple inflammatory programs.
 Biomarker discovery for a Phase II oral agent for the treatment of rheumatoid
arthritis and other inflammatory diseases
 PD biomarker representative on 3 late-stage pre-clinical projects consisting of
scientists & clinicians representing Discovery Research, PK/PD and Pre-clinical
functions.
 Discovered and developed a PD assay in support of a novel oral agent for the
treatment of rheumatoid arthritis and currently managing it’s transition to a
clinical CRO to support first-in-man studies.
 Championed the development of new technologies to measure cytokine release in
whole blood assays in a clinical setting.
2. Drug discovery focusing on novel therapies for rheumatoid arthritis &
asthma.
 Championed and co-led a novel drug discovery project targeting a purinergic
receptor and key regulator of inflammatory cytokine production. Project accepted
into Roche drug discovery portfolio in 2005 and a compound selected for entry
into man in Sep 2009.
 Proposed a new drug discovery project targeting a novel protein kinase and key
regulator of T cell and myeloid function for the treatment of rheumatoid arthritis
& asthma. Project accepted into the Roche research portfolio in 2007. Currently
serving as Project Team Leader, and have coordinated the successful completion
of a high throughput screen and the identification of novel chemical scaffolds for
the initiation of medicinal chemistry activities.
 Evaluated multiple RNAi techniques for utility in primary immune cells, both to
validate targets and as potential therapeutics
 Developed multiple in vitro assays of innate and adaptive immunity to assess the
relative potential of novel drugs to modulate the immune system. Coordinated a
matrix group of 17 biologists to support these assays as part of on-going drug
discovery activities.
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Roche Palo Alto representative to the Roche Functional Genomics Network, a
global team focused on implementing novel genomic technologies in drug
discovery.
Member of Roche Palo Alto Discovery Sciences and Technologies Management
Team, a cross-functional leadership team responsible for delivering drug
discovery support services to all Roche Palo Alto projects.
2002-2005
Research Scientist II, Genetics & Genomics,
Roche Palo Alto, LLC.
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Led a group of 3 scientists supporting target identification and validation in the
area of inflammation and autoimmunity.
Implemented siRNA and shRNA technologies in the Genetics & Genomics
Group. Numerous genes (e.g. JNK, p38, CD19) were successfully targeted in
multiple cell lines and primary human cells.
Hired 2 new scientists to build a functional genomics group with the expertise
required to carry out in vivo lentiviral shRNA experiments.
Team successfully introduced screened shRNAs against CD19 into murine single
cell embryos and recovered viable pups.
Applied genomic profiling technologies to support the differentiation of novel
drug candidates.
Used gene microarray profiling, rat genetics and rheumatoid arthritis disease
models to identify candidate genes for arthritis susceptibility and severity. This
project required extensive liaison with outside collaborators.
Member Institutional Animal Care and Use Committee(IACUC) responsible for
overseeing all experimental animal protocols and implementing US Federal
animal care regulations at Roche Palo Alto.
Member of the CNS Therapy Area Management Team, and the Discovery &
Sciences Technologies Management Team. Role on these teams was to ensure
that the Therapy Areas were aware of, understood and had full access to the
technologies within Genetics & Genomics and that they were utilized effectively.
One of only 3 people within the Genetics & Genomics organization chosen to
participate in the Roche Global Mobilizing Leaders initiative. This initiative was
aimed at supporting the development of high-potential leaders in Roche Research.
Led the entire Functional Biology Group of 8 FTEs whilst the other team leader
was on an extended maternity leave.
1998-2002
Project Leader – OATS (Osteoarthritis Target Search)
Department of Arthritis & Inflammation Genomics, Pharmacia Corp.
The goals of the OATS project were:
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Identify specific OA disease progression biomarkers for the clinical evaluation of
DMOADS, in particular inhibitors of inducible nitric oxide synthase (iNOS) and
matrix metalloproteases (MMPs).
Develop the next generation of DMOAD (disease modifying osteoarthritis drugs)
targets by identifying the genes/proteins that contribute to the pathogenesis of OA.
Accomplishments:
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Implemented spontaneous and surgical animal models of OA in-house. Namely,
the Hartley Guinea pig spontaneous model and a partial meniscal tear surgical
model in the rat.
Evaluated novel gene profiling technologies e.g. RADE (rapid analysis of
differential gene expression).
Successful transfer of genomic technology from external partners e.g Laser
Capture Micro-dissection.
Optimized technologies for transcriptional profiling, in particular, effective RNA
extraction from cartilage and bone, RNA amplification and probe preparation for
Incyte microarrays.
In collaboration with a Bioinformatician analyzed extensive microarray data and
developed comprehensive differential gene expression profiles for the rat surgical
and guinea pig spontaneous models of OA. Preliminary lists were also compiled
for a surgical canine OA model.
Mined commercial human databases for genes that are differentially regulated
during OA disease and filed provisional patents.
Initiated central tissue banking effort to obtain human joint tissues to support
multiple target validation and drug discovery projects.
Recruited international Consultants to aid in OA Biomarker validation and
discovery.
Participated in reviews of licensing opportunities related to new target
identification
Member of Arthritis & Inflammation Leadership Team. The function of this team
included the setting of strategic direction for the therapeutic area.
Scientific supervision of 4 scientists on the OATs project team as well as line
management for 1 other.
Additional Contributions
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Conducted gene expression studies in animal models of rheumatoid arthritis,
osteoarthritis and bone disease in support COX-2 and DMOAD drug discovery
projects. Developed species-specific reagents to assess the expression of diseaselinked genes in these model systems.
Completed Microsoft project training and implemented GANTT charts for OATs
project management.
Completed Incyte database technology training.
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Represented Pharmacia Discovery on Project Eagle, a cross-functional initiative
to optimize the early drug discovery process. Contributed on a committee of
representatives from all business units to design how Pharmacia can best discover,
develop and utilize biomarkers.
1995-1998
Postdoctoral Research Fellow
Dept. of Neuroscience
UPENN School of Medicine, Philadelphia. PA 19104
Principal Investigator: Professor E. Bryan Crenshaw III
Responsible for the derivation and characterization of transgenic and knockout
mice. One of the knockouts in particular (Brn-4 null mice) had a subtle and
unexpected phenotype that was only discovered through vigilant observation of
the mice. The predicted neural phenotype was not observed, but the mice showed
a 10 decibel reduction in hearing acuity and “head bobbing” that was found to be
coincident with changes in the morphology of the inner and middle ear.
Ultimately, demonstrated that Brn-4 null mice were phenotypically identical to Slf
mice (sex linked fidget mice – a result of X-ray mutagenesis) due to Slf mice
having a disrupted optic specific enhancer region for the Brn-4 gene. This
investigation involved considerable histology, immunohistochemistry, in situ
hybridization, promoter analysis as well as gross pathology.
1994-1995
Postdoctoral Research Fellow
Dept. of Craniofacial Development
Guy’s and St Thomas’s United Medical and Dental Schools. London, UK
Principal Investigator: Professor Paul Sharpe
Responsible for the design, construction and use of vectors to analyze the role of
Msx (homeobox) genes in the specification of tooth initiation and development
using both ectopic expression and targeted gene disruption in mice
1991-1994
Ph.D Graduate Student
Dept. of Cell Biology and Experimental Pathology
Institute of Cancer Research, London, UK.
Advisor: Dr. Trevor Dale
Used Northern analysis to demonstrate that some members of the Hox and Msx
class homeobox gene families are regulated across developmental boundaries in
the mouse mammary gland and in response to hormonal changes. This work
involved considerable handling of animals. Tissue culture techniques were used to
study gene regulation in vitro. Additionally, cDNA libraries were constructed for
differential screening.
Further techniques used included: in situ hybridization (both sections and whole
mounts), immunohistochemistry and RNase protection assays.
1987-1991
Scientific Officer, Wellcome Diagnostics
Dept. Of Molecular Biology
Beckenham, Kent. UK
Main responsibilities included the cloning and bacterial expression of HIV and
Hepatitis C proteins for use in diagnostic assays. This involved establishing new
ELISAs for the analysis of the recombinant proteins together with confirmatory
Western blot assays. In addition to devising fermentation conditions to maximize
the yield of protein for production purposes. Other responsibilities included the
training and supervision of junior staff.
Professional Activities:
Session Chair, Bone and Cartilage Genetics Meeting, Davos, Switzerland, March
2003.
Session Chair, Drug Discovery for Inflammatory Diseases, July 2003, Vienna VA.
Society Memberships:
2000- 2005 Osteoarthritis Research Society International (OARSI)
Publications:
Emerson R, Sherwood A, Desmarais C, Malhotra S, Phippard D, Robins H. (2013).
Estimating the ratio of CD4+ to CD8+ T cells using high-throughput sequence data. J
Immunol Methods. 2013 Feb 18.
Du Toit G, Roberts G, Sayre PH, Plaut M, Bahnson HT, Mitchell H, Radulovic S, Chan
S, Fox A, Turcanu V, Lack G, Learning Early About Peanut Allergy (LEAP) Study
Team. (2013) Identifying infants at high risk of peanut allergy: the Learning Early About
Peanut Allergy (LEAP) screening study. J Allergy Clin Immunol. 2013 Jan;131(1):13543.
Scadding GW, Calderon MA, Bellido V, Koed GK, Nielsen NC, Lund K, Togias A,
Phippard D, Turka LA, Hansel TT, Durham SR, Wurtzen PA. (2012) Optimisation of
grass pollen nasal allergen challenge for assessment of clinical and immunological
outcomes. J Immunol Methods. 2012 Oct 31;384(1-2):25-32.
Long SA, Rieck M, Sanda S, Bollyky JB, Samuels PL, Goland R, Ahmann A,
Rabinovitch A, Aggarwal S, Phippard D, Turka LA, Ehlers MR, Bianchine PJ, Boyle
KD, Adah SA, Bluestone JA, Buckner JH, Greenbaum CJ (2012) Rapamycin/IL-2
combination therapy in patients with type 1 diabetes augments Tregs yet transiently
impairs β-cell function. Diabetes. 61(9):2340-8.
Waubant E, Pelletier D, Mass M, Cohen JA, Kita M, Cross A, Bar-Or A, Vollmer T,
Racke M, Stüve O, Schwid S, Goodman A, Kachuck N, Preiningerova J, WeinstockGuttman B, Calabresi PA, Miller A, Mokhtarani M, Iklé D, Murphy S, Kopetskie H, Ding
L, Rosenberg E, Spencer C, Zamvil SS; ITN STAyCIS Study Group; ITN020AI Study
Management Team (2012) Randomized controlled trial of atorvastatin in clinically
isolated syndrome: the STAyCIS study. Neurology. Apr 10;78(15):1171-8.
Maecker HT, McCoy JP Jr; FOCIS Human Immunophenotyping Consortium, Amos M,
Elliott J, Gaigalas A, Wang L, Aranda R, Banchereau J, Boshoff C, Braun J, Korin Y,
Reed E, Cho J, Hafler D, Davis M, Fathman CG, Robinson W, Denny T, Weinhold K,
Desai B, Diamond B, Gregersen P, Di Meglio P, Nestle FO, Peakman M, Villanova F,
Ferbas J, Field E, Kantor A, Kawabata T, Komocsar W, Lotze M, Nepom J, Ochs H,
O'Lone R, Phippard D, Plevy S, Rich S, Roederer M, Rotrosen D, Yeh JH. (2010). A
model for harmonizing flow cytometry in clinical trials. Nat. Immunol. Nov;11(11):9758. Erratum in: Nat Immunol. 2010 Nov;11(11):979
Newell KA, Phippard D, Turka LA.(2011). Regulatory cells and cell signatures in
clinical transplantation tolerance. Curr Opin Immunol. 2011 Oct;23(5):655-9.
Hill, R.J., Dabbagh, K., Phippard, D. Li, C., Suttman, R.T., Welch, M., Papp, E., Song,
K.W., Chang, K.C., Leaffer, D., Kim, Y. N., Roberts, R.T., Zabka, T. S., Aud, D., Dal
Porto, J., Manning, A. M., Peng, S. L., Goldstein, D.M. & Wong, B. (2008) Pamapimod,
a novel p38 mitogen-activated protein kinase inhibitor: preclinical analysis of efficacy
and selectivity. J. Pharmacol. Exp. Ther. 327(3):610-9.
Phippard, D. & Manning A.M. Screening for inhibitors of transcription factors using
luciferase reporter genes in transfected cells. Chp 3 in: Methods Mol Biol, (2003) 225:
19-23
Gerstenfeld, L.C., Theide, M., Seibert, K., Mielke, C., Phippard, D. Tewari, S., Svagar,
B., Cullinane, D and Einhorn, T.A. (2003) Differential Inhibition of Fracture Healing By
Non-Selective and Cyclo-oxygenase-2-selective Non-Steroidal Anti-inflammatory Drugs.
Journal of Orthopeadics Research. 21(4):670-5.
Phippard, D., Boyd, Y., Reed V., Fisher, G., Masson, W.K, Evans, E.P., Saunders, J.C.
and Crenshaw III, E.B. (2000). The sex-linked fidget mutation abolishes Brn4/Pou3f4
gene expression in the embryonic inner ear. Human Molecular Genetics 9(1):79-85.
Phippard, D., Lu, L., Lee, D., Saunders, J.C. and Crenshaw III, E.B. (1999). Targeted
mutagenesis of the POU-domain gene Brn4/Pou3f4 causes developmental defects in the
inner ear. Journal of Neuroscience 19 (14):5980-9.
Phippard, D., Heydemann, A., Lechner, M., Lu, L., Lee, D., Kyin, T. and Crenshaw III,
E.B. (1998). Changes in the subcellular localization of the Brn4 gene product precede
mesenchymal remodeling of the otic capsule. Hearing Research 120(1-2):77-85.
Phippard, D.J., Weber-Hall, S.J., Sharpe, P.T., Naylor, M.S., Jayatalake, H., Maas, R.,
Woo, I., Roberts-Clark, D., Francis-West, P.H., Liu, Y.H., Maxson, R., Hill, R.E. and
Dale, T.C. (1996). Regulation of Msx-1, Msx-2, Bmp-2 and Bmp-4 during foetal and
postnatal mammary gland development. Development 122(9):2729-37.
Niranjan, B., Buluwela, L., Yant, J., Perusinghe, N., Atherton, A., Phippard, D., Dale,
T., Gusterson, B. and Kamalati, T. (1995). HGF/SF: a potent cytokine for mammary
growth, morphogenesis and development. Development 121(9):2897-908.
Barker, K.T., Martindale, J.E., Mitchell, P.J., Kamalati, T., Page, M.J., Phippard, D.J.,
Dale, T.C., Gusterson, B.A. and Crompton, M.R. (1995). Expression patterns of the novel
receptor-like tyrosine kinase, DDR, in human breast tumours. Oncogene 10(3):569-75.
Weber-Hall, S.J., Phippard, D.J., Niemeyer, C.C. and Dale, T.C. (1994). Developmental
and hormonal regulation of Wnt gene expression in the mouse mammary gland.
Differentiation 57(3):205-14.
Phippard, D., Sharpe, P. and Dale, T.C. (1994). Msx gene regulation during mouse
mammary gland development. In 1994 Hannah Symposium: Intercellular signaling in the
mammary gland. Edited by Wilde, C. J., Peaker, M. and Knight, C. H. Plenum Press
Riezu-Boj, J.I., Parker, D., Civeira, M.P., Phippard, D., Corbishley, T.P., Camps, J.,
Castilla, A. and Prieto, J. (1992). Detection of hepatitis C virus antibodies with new
recombinant antigens: assessment in chronic liver diseases. Journal of Hepatology
15(3):309-13.
Presentations/Abstracts:
M.H Shamji, J. A Layhadi, D.K.M Cheung, S.Q Khan, D. Phippard and S.R Durham
(2011) Grass Pollen Allergen-induced Surface Expression of CD203c, CD63 and
CD107a on CRTH2+ Basophils: Novel Biomarkers for Monitoring Efficacy of Allergenspecific Immunotherapy. World Allergy Congress
Accepted 2011 ACR
Immunoglobulin Concentrations and Infection Risk Among Patients with ANCAAssociated Vasculitis Treated with Rituximab or Cyclophosphamide. ACR/ARHP
Annual Scientific Meeting
Stone J, Merkel P, Seo P, Spiera R, Langford C, Hoffman G, Kallenberg C,
St. Clair EW, Fessler B, Tchao N, Webber L, Ding L, Sejismundo L, Mieras
K, Ikle D, Phippard D, Jepson B, Lail A, Asare A, Lim N, Mueller M, Brunetta P, Allen
N, Fervenza F, Geetha D, Keogh K, Kissin E, Monach P, Peikert T, Stegeman C,
Ytterberg S, and Specks U for the RAVE-ITN Research Group. Long-term results of the
RAVE Trial: Which disease subsets are at greatest risk for disease flare?
(2011 ACR abstract selected for oral presentation)
S. Alice Long, Srinath Sanda, Jane Buckner, Jennifer Bollyky, Robin Goland, Peter
Bianchine, Deborah Phippard, Mario Ehlers and Carla Greenbaum (2011). Rapamycin
plus IL-2 combination therapy in subjects with T1D results in a sustained increase in IL-2
responsiveness and a transient decrease in c-peptide levels. Federation of Clinical
Immunology Societies (FOCIS)
S Feng, J Punch, J Reyes, J Levitsky, G B Klintmalm, M Zimmerman, M Philogene, D
Phippard, P Sayre, M DesMarais, H Kopetskie, N Bridges, A Shaked, (2011). Evolution
of donor specific alloantibodies (DSA) with immunosuppression (IS) withdrawal among
adult liver transplant recipients in ITN030ST. The 2011 Joint International Congress of
ILTS, ELITA, & LICAGE
S Feng, U Ekong, S Lobritto, A Demetris, P Rosenthal, E Alonso, D Ikle, M Philogene, D
Phippard, and N Tchao. (2011) Clinical and Histological Predictors of Operational
Tolerance in Pediatric Liver Transplant Recipients. American Transplant Congress
(ATC)
Noha Lim, Sai Kanaparthi, Suzanne Mertens, Nishant Gopalakrishnan, Zhong Gao,
Zhugong Liu, Katarzyna Bourcier, Deborah Phippard, Adam Asare (2010) Automated
quality assessments of un-gated flow cytometry FCS files in a clinical trial setting.
International Society for the Advancement of Cytometry (ISAC)
Mary Carmelle Philogene, Hodan Ali, Adam Asare, Noha Lim, Smita Asare, Kasia
Bourcier, Deborah Phippard (2010). Banking RNA for Biomarker Discovery: Assessing
RNA Quality and Yield for Long Term Use. Federation of Clinical Immunology Societies
(FOCIS)
Zhong Gao, Adam Asare, Deborah Phippard, Vincent Carey (2010).Experimental
design and quality assurance of high-throughput clinical transplantomics studies: A
crucial step toward robust biomarker discovery. International Conference on
Transplantomics and Biomarker in organ transplantation
Scientific Advisory Board for Conference“Drug Discovery for Inflammatory
Diseases” June 2003, Vienna, VA. Chaired workshop “Gene Expression and Proteomic
Profiling for Inflammation Research
Phippard, D., Sharpe, P. and Dale, T. (1994). Developmental regulation of homeobox
genes in the mouse mammary gland.
Corbishley, T., Phippard, D., Mason, R., O’Callaghan, S., Doyle, D., Jeffrey, D. and
Rodgers, B. (1991). The use of structural antigens and PCR to resolve doubtful anti-HCV
antibody results.
Phippard, D., Glazebrook, J., Rodgers, B., Garson, J. A., Briggs, M. and Parker, D.
(1990). Recombinant ELISA and PCR analysis of PT-NANBH serum samples.
Skidmore, S., Elias, E., Neuberger, J., Corbishley, T. and Phippard, D. (1990).
Confirmatory testing for anti-hepatitis C.
References: Available upon request