Lisa Smith Webb

Assistant Professor of Biology
Christopher Newport University
1 University Place, Newport News, VA  23606
Office: (757) 594-7056         Fax: (757) 594-7209
E-Mail: lwebb@cnu.edu


EDUCATIONAL BACKGROUND

Postdoctoral Fellow - The Jackson Laboratory (Bar Harbor, ME)

Ph.D. The University of Tennessee (Knoxville, TN)
Major:  Biomedical Sciences
Dissertation:  Positional Cloning of the psrt Mutations on Mouse Chromosome 7
M.Ed. The University of Georgia (Athens, GA)
Major:  Science Education
B.A.  Maryville College (Maryville, TN)
Major:   Chemistry
Senior Thesis: The a-Chymotrypsin Catalyzed Hydrolysis of p-Nitrophenyl Acetate
Distinguished Achievement in Chemistry Award


TEACHING EXPERIENCE

8/04 – present  Assistant Professor of Biology (Cell Biology, Biochemistry)
Christopher Newport University (Newport News, VA)
8/88 – 8/95  Science Teacher (Chemistry, Physics, Physical Science)
Shiloh High School (Gwinnett County, GA)
8/87 – 8/88  Collegiate and Secondary Level Tutor
Maryville College Learning Center (Maryville, TN)
8/85 – 8/87 Graduate Teaching Assistant
The University of Tennessee
Chemistry Department


RESEARCH EXPERIENCE

Current Research Projects (at Christopher Newport University):

Postdoctoral Projects (Mentor - Dr. Luanne L. Peters at The Jackson Laboratory)

1. The overall objective of my primary postdoctoral research project was to identify interacting cellular and biochemical pathways critical to the biogenesis and function of lysosome-related organelles and to define their roles in the pathogenesis of Hermansky-Pudlak Syndrome (HPS). HPS is a human disease characterized by defects in lysosome-related organelles (lysosomes, melanosomes, and platelet dense bodies).  These defects lead to prolonged bleeding, varying degrees of oculocutaneous albinism, and the accumulation of ceroid pigment in lysosomes. I utilized a combination of cellular, molecular, genetic, and biochemical techniques to identify the functions of a putative HPS-related gene called Lrod (Lysosome-related organelle development), including immunoprecipitation/recapture experiments, a yeast two-hybrid screen, targeted mutagenesis in embryonic stem cells, and classical genetic crosses.
 
2.  As part of The Jackson Laboratory’s Heart, Lung, Blood, and Sleep Disorders mutagenesis program, I designed and initiated a sensitized mutagenesis screen to identify genes and gene products interacting in the BLOC-2 biochemical pathway. I utilize ENU (N-ethyl-N-nitrosourea) mutagenesis in ruby-eye males to look for non-allelic noncomplementation as well as dominant and semidominant effectors (enhancers and suppressors). 
 
3.  I worked with Dr. Jane Barker to positionally clone a mutation called scat, short for “severe combined anemia and thrombocytopenia.”  scat is a juvenile lethal mutation showing non-Mendelian inheritance.  I refined the map position of the mutation using interspecific genetic crosses, tested candidate genes within the interval, and conducted experiments to better define the epigenetic effects influencing the scat phenotype.
 
4.  In collaboration with Dr. Kenneth Johnson’s laboratory, I set up an interspecific intercross to map deaf circler 2 Jackson (dfcr-2J), a hearing and balance defect mutation that spontaneously arose in our breeding colony.  I conducted a phenotypic analysis of the mutants and mapped the mutation to a small interval in the distal portion of Mouse Chromosome 7. The gene responsible for this mutation is Ush1c, the murine ortholog of the gene responsible for both human Usher Syndrome type IC and the nonsyndromic deafness disorder DFNB18.   This mutant represents the first mouse model of these diseases.

Dissertation Projects (Mentor: Dr. Dabney K. Johnson at the Oak Ridge National Laboratory)

1.  Dysmyelination Project.  I conducted a biochemical analysis of two strains of mutant mice and positionally cloned the mutation responsible for this neurological phenotype.  The psrt (for “profound seizure and runting”) locus is situated within the p-deletion complex in the proximal region of Mouse Chromosome 7.  I positionally cloned this locus by producing and assembling physical and transcriptional maps of the region and determining the temporal and tissue-specific expression patterns of the resulting candidate genes.  Sequence analysis and temperature gradient capillary electrophoresis experiments indicate mutations are present in the protein arginine methyltransferase 3 (prmt3) gene in the mutants.  Using bioanalytical techniques, I was able to show a lack of methylation of the single methylarginine residue of the myelin basic protein in the mutants.  These results lead to the conclusion that mutations in murine prmt3 cause dysmyelination in the mouse, which leads to the psrt phenotype.  This work, when completed, will further elucidate the complex process of myelination at the cellular, biochemical, and developmental levels.
 
2.  Obesity Project.  Using positional cloning techniques, we identified plo1 (renamed pfatp), a gene responsible for an obesity phenotype mapping to the distal end of the p-deletion complex in Mouse Chromosome 7 and exhibiting non-mendelian inheritance.  To initially narrow the genomic interval, we performed a biochemical analysis of mice carrying p-region chromosomal deletions of varying lengths to determine body fat, adiposity index, blood glucose levels and other indicators of altered metabolism.
 

Selected Awards and Honors

1997-2003 International Mammalian Genome Society Travel Awards (6 awards)
1998-2000 University of Tennessee Travel Awards (3 awards)
1995 Tandy Technology Scholars Award (National Finalist)
1994, ’92 Teacher of the Year Finalist (Shiloh High School; Gwinnett County, GA)
1985  American Institute of Chemists’ Student Recognition Award
1985  Distinguished Achievement in Chemistry Award (Maryville College)


Competitive Fellowships and Grants Awarded

2003-2004  Ruth L. Kirschstein National Research Service Award (NRSA)
National Institutes of Health
Award #1F32HL072254-01A1
“Genetic Analysis of Vesicle Trafficking Pathways”
2002-2003  Judith Graham Pool Postdoctoral Fellowship
National Hemophilia Foundation (1 of 4 national awards)
“Exploiting mouse models to elucidate the cellular and molecular mechanisms involved in the pathogenesis of platelet storage pool deficiencies”
1994   NSF Travel Grant to attend “Working Conference on Science for Students with Disabilities”
1994  AT&T Mini-Grant
To fund “Student Demonstrations: A Non-Traditional Approach to Science Learning” at Shiloh High School in Gwinnett County, GA
1992  U.S. Department of Energy TRAC Fellowship
For summer work at The Oak Ridge National Laboratory/Oak Ridge Institute for Science and Education


Professional Affiliations/Memberships


The National Science Teachers Association
The International Mammalian Genome Society
The Hermansky-Pudlak Syndrome Network
American Association for People with Disabilities
 

Advanced Coursework (Postdoctoral)

 
Short Course on Genome Sequence Analysis -- The Jackson Laboratory; June 16-22, 2004.
 
Experimental Genetics of the Laboratory Mouse in Cancer Research -- The Jackson Laboratory; August 17-27, 2003.
 

Publications

 
Gwynn, B., Martina, J.A., Bonifacino, J.S., Sviderskaya, E.V., Lamoreux, M.L., Bennett, D.C., Moriyama, K., Huizing, M., Helip-Wooley, A., Gahl, W.A., Webb, L.S., Lambert, A.J., Peters, L.L.  Reduced pigmentation (rp), a mouse model of Hermansky-Pudlak Syndrome, encodes a novel component of the BLOC-1 Complex.  Accepted for publication in Blood
 
Johnson, K.R., Gagnon, L.H., Webb, L.S., Peters, L.L., Hawes, N.L., Chang, B., and Zheng, Q.Y.  Mouse models of USH1C and DFNB18: phenotypic and molecular analyses of two new spontaneous mutations of the Ush1c gene. Human Molecular Genetics 2003; 12(23): 3075-86.
 
Dhar, M.S., Webb, L.S., Hauser, L., Johnson, D. and West, D.R. A novel ATPase on mouse chromosome 7 is a candidate gene for increased body fat.  Physiol Genomics. 2000; Nov 9; 4(1): 93-100.


Invited Seminars

 
Webb, L.S.  Diluted Coat Colors and Aberrant Platelets: What’s the Link? Immunology and Hematology Interest Group. February 17, 2004; The Jackson Laboratory; Bar Harbor, ME.
 
Webb, L.S. Of Mice and Men: Using Mouse Models to Dissect a Complex Human Disease.  Maryville College Alumni Science Symposium.  October 18-19, 2002; Maryville, TN.
 
Webb, L.S.  Genetic Analysis of Vesicle Trafficking Pathways Involved in the Pathogenesis of Hermansky-Pudlak Syndrome. Immunology and Hematology Interest Group. April 30, 2002; The Jackson Laboratory; Bar Harbor, ME.
 
Webb, L.S.  “The Psrt Mutations on Mouse Chromosome 7: Physical Mapping and Biochemical Analysis.” April, 1998; J.C. Self Research Institute/Greenwood Genetics Center; Greenwood, S.C.
 

Presentations

 
Webb, L.S., Gwynn, B., Ciciotte, S.L., Smith, R.S. and Peters, L.L.  ruby eye Acts Semidominantly to Affect HPS Pathways. 17th International Mouse Genome Conference. November 9-12, 2003; Braunschweig, Germany.  Abstract 125.
 
Webb, L.S., Gwynn, B., Ciciotte, S.L., and Peters, L.L. Genetic analysis of Hermansky-Pudlak syndrome mutants. Mouse Initiatives V: Genomics of Complex Systems in Biomedical Research.  July 30 – August 2, 2003; The Jackson Laboratory, Bar Harbor, ME.
 
Johnson, K.R., Gagnon, L.H., Webb, L.S., Peters, L.L., Hawes, N.L., Chang, B., and Zheng, Q.Y. Two New Mouse Mutations Provide Models of USH1C and DFNB18. The 44th Annual Short Course in Medical and Experimental Mammalian Genetics.  July 13-25, 2003; The Jackson Laboratory, Bar Harbor, ME.
 
Webb, L.S., Gwynn, B., Ciciotte, S.L., and Peters, L.L. Genetic analysis of Hermansky-Pudlak syndrome mutants. The Jackson Laboratory Scientific Staff Retreat.  June 3, 2003; The Bar Harbor Regency Hotel, Bar Harbor, ME.
 
Webb, L.S., Gwynn, B., Ciciotte, S.L., and Peters, L.L. Genetic Analysis of Hermansky-Pudlak Syndrome Mutants.  16th International Mouse Genome Conference. November 17–20, 2002; San Antonio, TX. Abstract 159.
 
Webb, L.S., Dhar, M.S., Hauser, L.J., Culiat, C.T., and Johnson, D.K. Identification and Mapping of Prmt3 and Tip30, Two Genes on Proximal Mouse Chromosome 7. 15th International Mouse Genome Conference.  October 21–24, 2001; Edinburgh, Scotland, U.K. Abstract 183.
 
Dhar, M.S., Webb, L.S., Hauser, L., West, D., and Johnson, D.K.  A Putative Aminophospholipid Transporter is Linked to the p Locus on Mouse Chromosome 7. 14th International Mouse Genome Conference.  November 6-9, 2000; Narita, Japan. Abstract A9. 
 
Webb, L.S., Dhar, M.S. and Johnson, D.K. Physical Mapping in the psr Region of Mouse Chromosome 7.  Tennessee 2000 Biomedical Engineering Conference. March 29-April 1, 2000; Knoxville, TN.
 
Webb, L.S., Sega, G.A. McNeilly, M.S. and Johnson, D.K. Analysis of Myelin Basic Protein in the Mouse Using GC-MS.  Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy. March12-17, 2000; New Orleans, LA.  Paper #1097.
 
Sega, G.A., Webb, L.S., Goss, K.C., Schryver, J.C. and Johnson, D.K. Determination of Serotonin in Blood and Brain Extracts of Normal and Mutant Mice Using HPLC Analysis with Fluorescence Detection.  Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy. March12-17, 2000; New Orleans, LA. Paper #1046.
 
Dhar, M., Webb, L., Smith, L., West, D. and Johnson, D.  Altered Body Fat Content in Mice Carrying Deletions Near the p Region on Mouse Chromosome 7.   North American Association for the Study of Obesity Annual Meeting. November 14-18, 1999; Charleston, SC.
 
Webb, L.S., Dhar, M.S. and Johnson, D.K.  Physical Mapping in the psr Region of Mouse Chromosome 7. 13th International Mouse Genome Conference. October 31-November 3, 1999; Philadelphia, PA. Abstract E57.
 
Dhar, M., Webb, L., Smith, L., West, D. and Johnson, D.  Evidence of a Paternally Imprinted Gene Affecting Body Weight in Mice on Mouse Chromosome 7.  13th International Mouse Genome Conference. October 31-November 3, 1999; Philadelphia, PA. Abstract A10. 
 
Webb, L.S., Sega, G.A. and Johnson, D.K.  Analysis of Fatty and Organic Acids in the Mouse Using GC-MS. Southeast Regional Meeting of the American Chemical Society. October 17-20, 1999; Knoxville, TN. Paper #174.
 
Sega, G.A., Webb, L.S., Goss, K.C., Schryver, J.C. and Johnson, D.K.  HPLC Analysis Used to Identify a Mouse Mutant Deficient in Plasma Serotonin. Southeast Regional Meeting of the American Chemical Society. October 17-20, 1999; Knoxville, TN. Paper #553.
 
Webb, L.S., Sega, G.A. and Johnson, D.K.  Analysis of Fatty Acids in Mice Using GC-MS.  UT/ORNL Joint Institute for Biological Sciences/Genome Science and Technology Colloquium. May 27, 1999; Knoxville, TN.
 
Webb, L.S., Sega, G.A. and Johnson, D.K.  Analysis of Fatty and Organic Acids in the Mouse Using GC-MS.  Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy. March 7-12, 1999; Orlando, FL.  Paper #927.
 
Webb, L.S., Sega, G.A. and Johnson, D.K.  Analysis of Fatty Acids in the Mouse Using GC-MS.  12th International Mouse Genome Conference. September 30-October 3, 1998; Garmisch-Partenkirchen, Bavaria, Germany.  Abstract G13.
 
Dhar, M., Webb, L., York, B., West, D. and Johnson, D.  Physical Mapping of the Region on Mouse Chromosome 7 Homologous to Human Chromosome 15q11-q13. 12th International Mouse Genome Conference. September 30-October 3, 1998; Garmisch-Partenkirchen, Bavaria, Germany. Abstract A20.
 
Johnson, D.K., Goss, K.C., Sega, G.A., Schryver, J.C., Paulus, M.J., Ericson, M.N. and Webb, L.S.  ORNL’s Phenotype Screening Center. Mouse Molecular Genetics. Cold Spring Harbor Laboratory.  September 2-6, 1998; Cold Spring Harbor, NY.
 
Rinchik, E.M., Carpenter, D.A., Webb, L.S., Ji, Y., Nicholls, R.D. and Johnson, D.K.  Regional Mutagenesis with Hemizygosity Screening and N-Ethyl-N-Nitrosourea (ENU): New Data on the Pink-Eyed Dilution (p) Region of Mouse Chromosome 7. Mouse Molecular Genetics. Cold Spring Harbor Laboratory.  September 2-6, 1998; Cold Spring Harbor, NY.
 
Webb, L.S., Sega, G.A. and Johnson, D.K.  Analysis of Fatty Acids in Plasma Using GC-MS: An Integral Part of an Applied Cloning Strategy. Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy.  March 1-6, 1998; New Orleans, LA.  Paper #632.
 
Webb, L.S..  “Psr:  A Profound Seizure Phenotype Mapping Near the Mouse p Locus.” Greenwood Genetics Center & Oak Ridge National Laboratory Workshop.  November, 1997; Oak Ridge, TN.
 
Webb, L.S., Carpenter, D.A., Rinchik, E.M. and Johnson, D.K.  A Profound Seizure Phenotype Maps Near the Mouse p Locus. 11th International Mouse Genome Conference.  October 12-16, 1997; St. Petersburg Beach, FL.


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