Paul N. Hengen, Ph.D.
hengen@[EMAIL PROTECTED]
Summary:
Analytical Molecular Geneticist with extensive experience
in the following:
+ Genomic DNA analysis
+ Bioinformatics
+ Genotyping and data formatting
+ Genetic Engineering
+ Mathematical modeling
+ Algorithm development
+ PERL programming
WORK EXPERIENCE:
2006-Present, Staff Scientist, Institute for Genetic
Medicine, USC - Keck School of Medicine, Los Angeles, CA
-> As part of a team worked in collaboration with wet bench
scientists to identify molecular markers of prostate cancer
progression and metastasis to bone. Using a combination of
chromatin immunoprecipitation methods (ChIp-chip) and
bioinformatic techniques, we were able to identify human
genes associated with prostate cancer and understand the
control of these genes through specific transcription factor
binding sites.
2000-Aug 2005, R&D Scientist / Senior Software Engineer,
Applied Biosystems, Foster City, CA -> For this biotech
instrument company, personally designed the genetics object
model for ABI's instrumentation and data analysis software.
This object-oriented domain model, based on fundamental
principles of Mendelian characterization, was designed to be
independent of instrumentation. The design allows for
genetic data to be gathered from phenotype, genotype, and
gene expression information sources and then combined for
the purpose of association studies, mathematical modeling,
and data-mining. The genetics object model was specifically
designed to aid the discovery of new predictors of genetic
processes (biomarkers) and for applications in molecular
medicine.
Designed a genotype quality control system that enables one
to detect genotyping errors in datasets by creating unique
consensus allele calls per test subject. Genotype data can
then be passed directly into pedigree checking programs and
other error-trapping algorithms for further refinement and
analysis, with a turnaround time of minutes as compared with
weeks or months of data preparation. Accomplishment: The
genetics object model and genotype quality control mechanism
were implemented in a genotype management software
application named BioTrekker.
1999-2000, NIH National Research Service Award (NRSA) Fellow
in Human Genetics, Department of Neurology, Gallo Clinic and
Research Center - UCSF, Emeryville, CA -> As part of a team
developed and implemented a relational database to track the
flow of genetic information from the clinic through the
laboratory. Personally wrote in PERL an automated high-
throughput system for gathering genotype data of PCR
amplified DNA fragments from family members of patients
undergoing addiction treatment. Accomplishment: Using a
variety of linkage analysis techniques, the team was able to
map human genes associated with alcoholism and addiction.
1998-1999, Independent Consultant for Database Development
and Maintenance -> As an independent consultant, helped
several companies develop databases for Internet access.
This included database structure development for indexing
molecular biology citation abstracts, database management
for on-line molecular biology catalogs, programming for
database management in Pascal (~ 70 programs; ~10,000 lines)
and PERL (~ 110 programs; ~29,000 lines), and data entry
using Microsoft Excel and Microsoft Access. Also designed
several Internet pages using HTML.
1992-1998, NIH Intramural Research Trainee Award (IRTA)
Fellow, Senior Staff Fellow, and Consultant at the National
Cancer Institute Laboratory of Experimental and
Computational Biology, National Cancer Institute, Frederick,
MD -> As part of a team used information theory techniques
to create mathematical models of DNA binding sites. By
comparing the models to natural binding sites, made
predictions about the properties of DNA-protein
interactions concerning transcriptional regulation (gene
expression) and other molecular recognition. Showed the
feasibility of using such a method for scanning DNA
sequences to predict sites bound by the Factor for Inversion
Stimulation (Fis), a pleiotropic protein that enhances site-
specific recombination, controls DNA replication, and
regulates transcription of a number of genes in Escherichia
coli and Salmonella typhimurium.
As part of a team developed a general sequence analysis
program that can be used to investigate the effects of
particular mutations. With this new tool, one can
interactively alter the DNA sequence to quantitatively
engineer binding sites to one's own specifications, predict
whether a change is likely to be a polymorphism or a
mutation, and detect anomalies in sequence databases. These
techniques were applied to engineer gene regulatory systems
de novo and design experiments to prove theoretical concepts
with customized DNA binding assays.
Accomplishments: Provided proof of concept with laboratory
bench experiments. Identified new biologically im****tant DNA
binding sites. Authored over 45 articles published as a
`Methods and Reagents' monthly series within Trends in
Biochemical Sciences from 1993 through 1997. Co-inventor of
a component for a molecular computing device: US Patent
6,774,222 and European Patent 1057118.
1991-1992, Post-doctoral Fellow in Molecular Genetics,
Carleton University, Ottawa, Canada -> Previously cloned the
kikA region of the multiple antibiotic resistance plasmid
pCU1 isolated from a hospital burn patient. The expression
of kikA in K. oxytoca under control of the strong inducible
E. coli tac promoter results in loss of cell viability. Two
open reading frames (ORFs) were identified within the kikA
region of pCU1 that may contribute to the killing of
Klebsiella oxytoca by conjugation. The first ORF codes for a
putative polypeptide of 104 amino acids. The second ORF
codes for a 70 amino acid polypeptide. Personally extended
Ph.D. studies on the kikA region by over expressing the kikA
gene through translational gene fusions and site-specific
mutagenesis utilizing a phagemid technique.
1985-1991, Ph.D. in Molecular Genetics, Carleton University,
Ottawa, Canada -> Transfer of the IncN group plasmid pCU1
from Escherichia coli to Klebsiella oxytoca by conjugation
kills a large pro****tion (90-95%) of the recipients of
plasmid DNA whereas transfer to E. coli does not. Two
regions, kikA and kikB, were identified on pCU1 that
contribute to the Kik (killing in Klebsiella) phenotype.
Personally cloned, sequenced, and characterized kikA, a
genetic region of IncN group plasmid pCU1 required for
killing of Klebsiella oxytoca.
1983-1985, M.S. in Microbiology , University of Vermont,
Burlington, VT -> The Gram-negative bacterium Rhizobium loti
symbiotically fixes atmospheric nitrogen with Lotus
corniculatus (birdsfoot trefoil), a highly nutritive
leguminous plant commonly found in grazing pastures. Used
Transposon Tn5 for mutagenesis in R. loti in order to
isolate auxotrophic and symbiotic mutants, facilitating
agricultural studies of symbiotic nitrogen fixation.
1978-1983, B.S. in Microbiology, University of Maryland,
College Park, MD
ADDITIONAL COURSES AND ACTIVITIES:
* Bioinformatics and Data-Mining at University of California
at Berkeley
* Statistical Learning and Data-Mining at Stanford
University
* Object-Oriented Analysis and Design Advanced Technology
Training at Valtech
* Requirements Elicitation and Facilitation at IconMediaLab
* PCR and Molecular Hybridization Technology sponsored by
the Foundation for Advanced Education in the Sciences
(FAES) at NIH
* Cellular and Molecular Approaches to the Study of Cancer
and Genetic Diseases sponsored by the FAES at NIH
* DNA binding proteins and Homeoboxes sponsored by the FAES
at NIH
* Advanced Immunology in the Biomedical Science Program at
Hood College
COMPUTER SKILLS:
Windows95/98/NT/2000/XP, UNIX, Linux, DOS, Mac,
Object-Oriented design using UML, Rational Rose, Fortran,
Pascal, PERL, some C and Java experience, MS Excel, MS
Access, XML, WordPerfect, MS Word, LaTeX, HTML, PostScript,
CorelDraw, Delila (DNA Library Language), PCR primer design
using Primer3 and Primer Express, Phred/Phrap, Consed
PUBLICATIONS AND PRESENTATIONS:
Hengen, P. N., Lyakhov, I. G., Stewart, L. E. and T. D.
Schneider. 2003. Molecular flip-flops formed by overlapping
Fis sites. Nucleic Acids Research. 31(22):6663-6673.
Lyakhov, I. G., Hengen, P. N., Rubens, D. and T. D.
Schneider. 2001. The P1 phage replication protein RepA
contacts an otherwise inaccessible thymine N3 proton by DNA
distortion or base flipping. Nucleic Acids Research.
29(23):4892-4900. *Note: We also ma
Hengen, P. N., Bartram, S., Stewart, L., and T. D.
Schneider. 1997. Information Analysis of Fis Binding Sites.
Nucleic Acids Research. 25(24):4994-5002.
Hengen, P. N. and T. D. Schneider. 1997. Scanning Genomes
for Binding Sites: Sequence "Walkers" Display the
Information Content of Individual Sites. Presented at "The
Fourth Annual Human Genome Project: Commercial Implications"
San Francisco, CA, USA Febr
Hengen, P. N. 1995. Mini-prep plasmid DNA isolation and
purification using silica-based resins. In: A. M. Griffin
and H. G. Griffin (eds.) "Molecular Biology: Current
Innovations and Future Trends" Horizon Scientific Press,
Wymondham, Norfolk, UK pp. 39-4
Hengen, P. N. and V. N. Iyer. 1992. DNA cassettes containing
the origin of transfer (oriT) of two broad-host-range
transfer systems. Biotechniques 13:56-62. * Note: The DNA
cassette containing plasmids pUC1813-NoriT (ATCC No. 77276)
and pNH-Kan/oriT (ATCC
Hengen, P. N., D. Denicourt, and V. N. Iyer. 1992. Isolation
and characterization of kikA, a region on IncN group
plasmids that determines killing of Klebsiella oxytoca. J.
Bacteriol. 174:3070-3077.
Kuykendall, L. D. and P. N. Hengen. 1988. Microbial Genetics
of Legume Root Nodulation and Nitrogen Fixation. pp.71-111.
In: Biological Nitrogen Fixation: Recent Developments. N. S.
Subba Rao (ed.). Oxford and IBH Publi****ng Company, New
Delhi, India.
Hengen, P. N. and W. W. Currier. 1986. Mutants of Rhizobium
loti induced by transposon Tn5 . Presented at "The Third
International Symposium on the Molecular Genetics of
Plant-Microbe Interactions" Montreal, Canada. July 1986.
Hengen, P. N. and W. W. Currier. 1985. Transposon Tn5
mutagenesis in Rhizobium loti. Presented at "Beltsville
Symposium X: Biotechnology for Solving Agricultural
Problems" Beltsville, Maryland. May 1985.
References available upon request
-Paul.
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