S S
Steven Shell

Steven M.
Shell

Associate Professor of Biology

Research Interests

The National Cancer Institute at the National Institutes of Health estimates  >70% of all human cancers result from exposure to environmental carcinogens. Many environmental carcinogens damage DNA and cause mutation, genomic instability, and ultimately disease.  Therefore, understanding how cells respond to these environmental insults is of critical importance to developing cancer treatments and prevention policies.  Cells have developed an arsenal of biochemical pathways, collectively termed the DNA damage response, to coordinate cellular activities to repair damaged DNA.  Excision repair is a powerful strategy to identify and remove covalent chemical modifications to DNA.  In excision repair, a section of DNA containing the lesion is removed and the resulting gap re-synthesized using the unmodified strand as a template.  Cells employ two types of excision repair, nucleotide excision repair (NER) and base excision repair (BER), to remove a broad spectrum of DNA lesions.

My long-term research interests focus on determining how protein-protein and protein-DNA complexes are assembled and remodeled to repair damaged DNA.  Understanding how these molecular machines are spatially and temporally organized is critical to elucidating their functions in biochemical pathways.
Determining how DNA repair activities are coordinated will provide details of the molecular mechanisms underlying carcinogenesis in humans.  Moreover, as many current anti-cancer agents act by inducing DNA damage, knowledge of the molecular mechanisms underlying DNA repair has the potential to provide new therapeutic strategies to enhance or improve upon current chemotherapies.
In my laboratory, we employ a wide variety of technologies to answer these questions.  In order to test how molecular machines function, we isolate repair proteins for biochemical, biophysical, and ultimately structural analysis of their machines.  We then use recombinant genetic systems in human cell cultures to verify and validate the results we obtain via biochemical analysis.

I strongly support and encourage research opportunities for undergraduate students.  Research in my laboratory provides an exciting training environment for young scientists.  Students actively participate in experimental design, data acquisition and analysis.  Program objectives are planned to allow for the research to progress in stages, providing adequate time for training students in necessary skills.  In addition to technical training, students also gain experience in scientific communication.  All students are taught and required to maintain well-organized laboratory notebooks.  Scientific writing skills will be developed through preparation of written laboratory reports and contributing to manuscripts for publication.  Oral presentation skills will be honed by presenting their research in regularly scheduled laboratory meetings and at appropriate internal and external research conferences.  I maintain an open-door policy for all members of my laboratory and establish regularly scheduled meetings with each individual student to develop and assess progress towards academic, research, and career goals.

Professional Interests

I am a molecular biologist with broad training ranging from cellular biology, biochemistry, and structural biology.

My first goal as an educator is to help students develop a firm understanding of the molecular nature of living systems.  This goal is reflected in the courses I teach at UVA Wise, which includes Topics in Cellular Biology, Molecular Genetics, and Developmental Biology.  My second goal is to assist students in becoming scientific communicators.  As such, reading and critical review of primary scientific literature, preparation of mock-manuscripts, and public presentation of scientific topics play a major role in my curricula.  In addition to my classroom activities I am currently establishing an independent research laboratory to continue my investigations of the molecular mechanisms underlying DNA damage repair.  A major advantage to being a faculty member at a small liberal arts college is the ability to work directly with undergraduate students, assisting in their exploration of various scientific disciplines, and providing novel frameworks for their growth and development into the next generation of scientists.

Awards

Grant Awards

PF-11-271-01-DMC (Shell, PI)  $150,000                 September 1, 2011 – August 18, 2014
American Cancer Society Molecular Genetics and Biochemistry of Cancer Program Postdoctoral Fellowship Award

1F32GM089022-01A1 (Shell, PI)  $50,474                June 1, 2010 – May 31, 2011
NIH/NIGMS Ruth L. Kirschstein National Research Service Award for Postdoctoral Fellows

Student Research Support

2015:  The University of Virginia’s College at Wise Fellowship in the Natural Sciences (FINS).
“Biochemical Characterization of the XPA-XPC Complex”.
Student:  Isaac Holyfield.

Academic and Professional Honors

  • 2013:  Second Place, Postdoctoral/Research Associate Oral Presentation,
  • 15th Annual Midwest DNA Repair Symposium
  • 2008-2010:  Vanderbilt University Center in Molecular Toxicology T32 Training Program in Environmental Toxicology Postdoctoral Research Associate Award
  • 2006:  Graduate Student Outstanding Oral Presentation, 8th Annual Midwest DNA Repair Symposium
  • 2006:  American Society of Biochemistry and Molecular Biology Graduate Student/Postdoctoral Travel Fellowship Award, FASEB Annual
  • Experimental Biology 2006

Selected Publications

Topolska-Woś AM, Shell SM, Kilańczyk E, Szczepanowski RH, Chazin WJ, and Filipek A.  2015.  A role for dimerization of CacyBP/SIP in the control of ERK1/2 phosphatase activity and response to oxidative stress. The FASEB Journal.  29(5):  1711-1724.

Hilton B, Shkriabai N, Musich PR, Kvaratskhelia M, Shell S, and Zou Y.  2014. A new structural insight into XPA-DNA interactions.  Bioscience Reports. 34(6):  831-840.

Shuck SC, Wauchope OR, Rose KL, Kingsley PJ, Rouzer CA, Shell SM, Sugitani N, Chazin WJ, Zagol-Ikapitte I, Boutaud O, Oates JA, Galligan JJ, Beavers WN, and Marnett LJ.  2014.  Chemical Research in Toxicology.  27(10):  1732-1742.

Sugitani N*, Shell SM*, Soss SE, and Chazin WJ.  2014.  Redefining the DNA-Binding Domain of Human XPA.  Journal of the American Chemical Society. 136(31):  10830-10833.

Shell SM, Hawkins EK, Tsai M-S, Hlaing AS, Rizzo CJ, and Chazin WJ.  2013. Xeroderma pigmentosum complementation group C protein (XPC) serves as a general sensor of damaged DNA.  DNA Repair.  12(11):  947-953.

Shell SM*, Li Z*, Skhriabai N, Kvaratskhelia M, Brosey C, Serrano MA, Chazin WJ, Musich PR, and Zou Y.  2009. Checkpoint kinase ATR promotes nucleotide excision repair of UV-induced DNA damage via physical interaction with xeroderma pigmentosum group A.  Journal of Biological Chemistry.  284(36): 24213-24222.

Meneni SR, Shell SM, Gao L, Jurecka P, Lee W, Spooner J, Zou Y, Chiarelli MP, Cho BP.  2007.  Spectroscopic and Theoretical Insights into Sequence Effects of Aminofluorene-Induced Conformational Heterogeneity and Nucleotide Excision Repair.  Biochemistry.  46(40):  11263-11278.

Liu Y, Wang Y, Rusinol AE, Sinensky MS, Liu J, Shell SM, and Zou Y.  2007. Involvement of xeroderma pigmentosum group A (XPA) in progeria arising from defective maturation of prelamin A.  The FASEB Journal.  22(2):  603-611.

Meneni S*, Shell SM*, Zou Y, Cho, BP.  2007.  Conformation-Specific Recognition of Carcinogen-DNA Adduct in Escherichia coli Nucleotide Excision Repair.  Chemical Research in Toxicology.  20(1):  6-10.

Wu X*, Shell SM*, Liu Y, Zou Y.  2007.  ATR-dependent checkpoint modulates XPA nuclear import in response to UV irradiation.  Oncogene.  26:  757-764.

Yang Z, Roginskaya M, Colis LC, Basu AK, Shell SM, Liu Y, Musich PR, Harris CM, Harris TM, Zou Y.  2006.  Specific and Efficient Binding of Xeroderma Pigmentosum Complementation Group A to Double-Strand/Single-Strand DNA Junctions with 3’- and/or 5’-ssDNA Branches.  Biochemistry.  45(51): 15921-15930.

Wu X, Shell SM, Yang Z, Zou Y.  2006.  Phosphorylation of nucleotide excision repair factor xeroderma pigmentosum group A by ataxia telangiectasia mutated and Rad3-related-dependent checkpoint pathway promotes cell survival in response to UV irradiation.  Cancer Research.  66(6):  2997-3005.

Wu X, Shell SM, Zou Y.  2005.  Interaction and colocalization of Rad9/Rad1/Hus1 checkpoint complex with replication protein A in human cells. Oncogene.  24(29):  4728-4735.

Shell SM, Hess S, Kvaratskhelia M, Zou Y.  2005.  Mass spectrometric identification of lysines involved in the interaction of human replication protein A with single-stranded DNA.  Biochemistry.  44(3):  971-978.

Zou Y, Ma H, Minko IG, Shell SM, Yang Z, Qu Y, Xu Y, Geacintov NE, Lloyd RS. 2004.  DNA damage recognition of mutated forms of UvrB proteins in nucleotide excision repair.  Biochemistry.  43(14):  4196-4205.

Zou Y, Shell SM, Utzat CD, Luo C, Yang Z, Geacintov NE, Basu AK.  2004. Effects of DNA adduct structure and sequence context on strand opening of repair intermediates and incision by UvrABC nuclease.  Biochemistry.  42(43):
12654-12661.

Invited Review Papers

Shell SM and Chazin WJ.  2012.  XPF-ERCC1:  On the Bubble.  Structure. 20(4):  566-568.

Zou Y, Liu Y, Wu X, Shell SM.  2006.  Functions of human replication protein A (RPA):  from DNA replication to DNA damage and stress responses.  J. Cell Physiol. (Invited Review).  208(2):  267-273.

Book Chapters

Shell SM and Chazin WJ.  2010.  Biochemical and Structural Domain Analysis of Xeroderma Pigmentosum Complementation Group C Protein.  Structural Biology of DNA Damage and Repair.  American Chemical Society.  1041:  59-71.

Shell SM and Zou Y.  2009.  Protein-protein interactions in Ataxia telangiectasia.  Molecular Mechanisms of Ataxia Telangiectasia.  Landes Biosciences.  42-51.

Shell SM and Zou Y.  2008.  Other Proteins Interacting with XP Proteins. Advances in Experimental Medicine and Biology.  Landes Biosciences.  637: 103-112.

*Equally contributing author

Presentations

March 17, 2014:  “The Ties That Bind: Investigations Into DNA-Protein Interactions”. Guest Lecturer, The University of Virginia’s College at Wise, Wise, VA.

May 18, 2013:  “Xeroderma pigmentosum complementation group C (XPC) protein serves as a generic sensor of damaged DNA”.  15th Annual Midwest DNA Repair Symposium, Lexington, KY.

June 06, 2011:  “DNA Damage Recognition in the Nucleotide Excision Repair Pathway”. Invited Speaker, Vanderbilt University Molecular Biophysics Training Program Seminar Series, Nashville, TN

May 21, 2006:  “ATR-dependent Checkpoint Modulates Nuclear Import of Nucleotide Excision Repair Factor XPA In Response to UV Irradiation”. 8th Annual Midwest DNA Repair Symposium, Indianapolis, IN.

September 20, 2004:  “A Mass Spectrometric Study of the Interaction of Human Replication Protein A with ssDNA”.  Invited Speaker, The University of Virginia’s College at Wise, Wise, VA.

June 6, 2004:  “Footprinting of RPA-ssDNA Interaction Using Mass Spectrometry”.  6th Annual Midwest DNA Repair Symposium, Lexington, KY.

March 31, 2001:  “Utility of 18s rDNA sequences for resolving ordinal-level relationships among Myxomycetes”.  Middle Atlantic States Mycology Conference, Athens, GA.

Education
Doctor of Philosophy, East Tennessee State University, College of Medicine, Biomedical Sciences/Biochemistry, Department of Biochemistry and Molecular Biology, 2008
Bachelor of Science, The University of Virginia’s College at Wise, Biology, Department of Natural Sciences, 2001
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