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Neil F. Box, Ph.D.

Assistant Professor


Departmental Associations:

Department of Dermatology
The Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology
University of Colorado Cancer Center
     Preceptor Topic:
Oncology
Colorado Clinical and Translational Sciences Institute (CCTSI)

 

Previous Faculty Appointments:

Department of Dermatology, Baylor College of Medicine, Houston, Texas

Current Laboratory Member:

Nema Sobhani

Research Assistant

Education: University of Colorado at Denver, Class of 2013
BS in Biology with Minors in Philosophy and Ethics

Bio:  I am a Dermatology Research Assistant in the Box Lab, under the supervision of Drs. Neil Box and Tamara Terzian since May of 2012, and I am currently a medical school candidate.  My research interests are in Melanoma and the tanning response governed by the p53 gene and other relevant biochemical pathways. I am also interested in the connection between the biological mechanisms of the tanning response and how they relate to public health with regard to preventing skin diseases in adolescents, who may be prone to later life susceptibility. 

I am passionate about connecting the music and arts community in Colorado to charities in order to help aim charitable interests of local artists, which led to my co-founding and chair position with Helping Hands, a local non-profit organization that strives to meet that exact objective.  Two of my favorite hobbies include playing guitar for two progressive rock bands, and audio engineering/producing in my DIY home recording setup.

​Education

     Ph.D., University of Queensland, Australia, Department of Biochemistry, 1998
     B.Sc. (Honors), University of Queensland, Australia, Department of Biochemistry, 1998  

Postdoctoral Training

Postdoctoral Fellow, Institute for Molecular Bioscience, University of Queensland, Australia, 1999 - 2001

Postdoctoral Fellow, Departments of Molecular and Human Genetics and Dermatology, Baylor College of Medicine, Houston, Texas, 2001 - 2004

 
The mouse as a model for human melanocyte and melanoma development

Melanocytes are the pigment producing cells within the skin. Melanocytes give rise to melanoma, a particularly invasive and deadly tumor type. In order to better understand genes that are important in melanoma risk and progression, we are interested in the important pathways that regulate development of melanoblasts, or melanocyte stem cells. Historically, many of the pathways that regulate melanocyte development, pigment production and propensity to transform to melanoma were discovered with investigation of mouse pigmentation mutations. We have assembled a number of mouse pigmentation mutations, identified through random insertional mutagenesis screens or mouse chemical mutagenesis screens that are involved in regulating melanocyte numbers within the skin. Investigation of the molecular basis of these mouse pigmentation phenotypes identifies new candidates genes and pathways that may control normal human pigmentation phenotypes. In order to test for the role of these genes in human pigmentation we have isolated DNA from a large collection of Colorado children who are part of a longitudinal study of melanocytic nevus development. Some of these children have been followed since 3 years of age with annual skin exams that have kept track of pigmentation phenotypes such as skin, hair and eye color, and numbers and size of incident and pre-existing melanocytic nevi. The majority of children are now 9 years of age. We are examining genetic polymorphisms in a number of important mouse melanocyte development pathways that may play a role in determining normal human pigmentation phenotypes and in melanoma risk. Our interests also include characterisation of the major gene expression differences between human melanoblasts isolated from foreskin, and differentiated melanocytes. We are comparing these gene expression profiles with those from malignant melanoma in order to investigate putative "melanoma stem cell" markers that may have therapeutic significance.
 
Image: E10.5 DCT-LacZ mouse embryo. β-Gal stain (blue) identifies individual melanoblasts in addition to neural and craniofacial sructures.  

Funding: 

  • NIH/NCI R01 Research Grant, PI: Crane  (4/1/10 - 01/31/15)
  • NIH/NCRR Research Grant, PI: Sokol, Pilot Grant, PI: Box   (5/01/13 – 4/30/18)
  • Colorado Cancer Fund, Community Engagement Pilot Project   (01/01/14 – 06-30-14)

​Selected Publications:

  1. N.F. Box, J.R. Wyeth, L.E. O’Gorman, N.G. Martin and R.A. Sturm. (1997) Characterisation of melanocyte-stimulating hormone receptor variant alleles in twins with red hair. Human Molecular Genetics, 6(11): 1891-1897.
  2. Richard A. Sturm, Neil F. Box, and Michele Ramsay. (1998) Human pigmentation genetics: the difference is only skin deep.  Bioessays, 20(9): 712-721.
  3. Palmer J.S.*, Duffy D.L.*, Box N.F.*, Aitken J.F., O'Gorman L.E., Green A.C., Hayward N.K., Martin N.G., Sturm R.A. (2000) Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype? American Journal of Human Genetics 66(1):176-186.
    *Equal contributions were made towards this work by the first 3 authors.
  4. Box N.F., Duffy D.L., Irving R.E., Russell A., Chen W., Griffyths L.R., Parsons P.G., Green A.C., Sturm R.A. (2001) Melanocortin-1 receptor genotype is a risk factor for basal and squamous cell carcinoma.  Journal of Investigative Dermatology 116(2):224-229.
  5. Box N.F., Duffy D.L., Chen W., Stark M., Martin N.G., Sturm R.A., Hayward N.K. (2001) MC1R genotype modifies risk of melanoma in families segregating CDKN2A mutations. American Journal of Human Genetics 69: 765-773.
  6. Voisey J., Box N.F., van Daal A. (2001) A Polymorphism Study of the Human Agouti Gene and Its Association with MC1R. Pigment Cell Research 14:264-267.
  7. Sturm R.A., Teasdale R.D., Box N.F., (2001) Human pigmentation genes: identification, structure and consequences of polymorphic variation. Gene 281(1-2):81-94.
  8. Box N.F. and Sturm R.A. (2001) Skin colour and skin cancer - the genetic link, Todays Life Sciences 15: 79-84.
  9. A.G. Smith*, N.F. Box*, L.H. Marks, W. Chen, D.J. Smit, J.R. Wyeth, G.A. Huttley, S. Easteal and R.A. Sturm (2001) The human melanocortin-1 receptor locus: analysis of transcription unit, locus polymorphism and haplotype evolution. Gene 281:81-94.*Equal contributions were made towards this work by the first 2 authors.
  10. Sturm R.A., Duffy D.L., Box N.F., Newton R.A., Shepherd A.G., Chen W., Marks L.H., Leonard H.J. and Martin N.G. (2003) Genetic association and cellular function of MC1R variant alleles in human pigmentation.  Annals of the New York Academy of Science 994: 348-358.
  11. Sturm R.A., Duffy D.L., Box N.F., Chen W., Smit D.J., Brown D.L., Stow J.L., Leonard H.J. and Martin N.G. (2003) The role of melanocortin-1 receptor polymorphism in skin cancer risk phenotypes.  Pigment Cell Research 16:266-272.
  12. Kile B.T., Hentges K., Clark A.T., Salinger A.P., Box N.F., Johnson R.L., Behringer R., Bradley A., Justice M.J. (2003) Functional genetic analysis of mouse Chromosome 11 by the large-scale isolation of recessive mutations using a balancer chromosome. Nature 425(6935):81-86.
  13. Duffy D.L., Box N.F., Chen W., Palmer J.S., Montgomery G., Green A.C., Martin N.G., and Sturm R.A. (2004) Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. Human Molecular Genetics 13(4):447-461.
  14. Terzian T., Wang Y., Box N.F., Van Pelt C.S., Lozano G. (2007) Haploinsufficiency of MDM2 and MDM4 in tumorigenesis and development. Molecular and Cellular Biology, 27(15):5479-5485.
  15. Liu G., Terzian T., Xiong S., Van Pelt C.S., Audiffred A., Box N.F., and Lozano G. (2007) The p53-Mdm2 network in progenitor cell expansion during mouse postnatal development Journal of Pathology 213(4):360-368.
  16. Box N.F. and Terzian T. (2008) The role of p53 in pigmentation, tanning and melanoma. Pigment Cell Melanoma Res. 21(5):525-533.
  17. Walker G. and Box N.F. (2008) Ribosomal stress, p53 activation and the tanning response. Expert Review of Dermatology, 3(6):649-656.
  18. Valentin-Vega YA, Box N., Terzian T, Lozano G. (2009) Mdm4 loss in the intestinal epithelium leads to compartmentalized cell death but no tissue abnormalities. Differentiation. 77(5):442-449.
  19. Aalborg J., Morelli JG., Mokrohisky ST., Asdigian N., Byers TE., Dellavalle RP., Box N.F., Crane LA. (2009) Tanning increases nevus development in light-skinned children without red hair. Archives of Dermatology 145(9):1-8.
  20. Chen D., Lin Q., Box N., Roop D., Ishii S., Matsuzaki K., Fang T., Hornyak T., Reed J., Stavnezer E., Timchenko N., Medrano E. (2009) SKI deficiency inhibits human melanoma tumor growth in vivo. Pigment Cell and Melanoma Research 22(6):761-772.
  21. Box N.F., Torchia EC, Roop DR. (2010) Are stem cell niches shared for skin cancers? Pigment Cell and Melanoma Research 23(4):517-520.
  22. Terzian T, Torchia EC, Dai D, Robinson SE, Murao K, Stiegmann RA, Gonzalez V, Boyle GM, Powell MB, Pollock PM, Lozano G, Robinson WA, Roop DR, Box N.F. (2010) p53 prevents progression of nevi to melanoma predominantly through cell cycle regulation. Pigment Cell and Melanoma Research 23(6):781-794.
  23. Walker G., Soyer H.P., Handoko H., Ferguson B., Kunisada T., Khosrotehrani K., Box N.F., Muller H.K. (2011) Superficial spreading-like melanoma in Arf-/-::Tyr-NrasQ61K::K14-Kitlg mice – Keratinocyte Kitl is sufficient to “translocate” melanomas from the dermis to the epidermis. Journal of Investigative Dermatology 131(6):1384-1387.
  24. Terzian T., Dumble M., Arbab F., Thaller C., Donehower L.A., Justice M.J., Roop D.R., Box N.F. (2011) Rpl27a mutation in the Sooty Foot Ataxia mouse phenocopies high p53 mouse models. Journal of Pathology (10-652), 224(4):540-552.
  25. Torchia E.C., Caulin C., Acin S., Terzian T., Kubick B.J., Box N.F., Roop D.R. (2011) Unraveling the pathways mediating the gain of function properties of mutant p53R172H in a mouse model of skin cancer. Oncogene. Epub ahead of print, October 3.
  26. Walker G.J., Soyer H.P., Terzian T., and Box N.F. (2011) Modeling melanoma subtypes in mice. Pigment Cell and Melanoma Research. 24(6):1158-1176.
  27. Gamble R.G., Asdigian N.L., Aalborg J., Gonzalez V., Box N.F., Huff L.S., Baron A.E., Morelli J.G., Mokrohisky S., Baron A., Crane L.A., Dellavalle R.P. (2012) Sun damage in ultraviolet photographs correlates with phenotypic melanoma risk factors in 12-year-old children. Journal of the American Academy of Dermatology 67(4):587-597.
  28. Tran A.D., Asdigian N.A., Aalborg J., Morelli J.G., Mokrohisky S., Box N.F., Dellavalle R., Berwick M., Crane L.A. (2012) Skin Cancer Perceptions, Sun Protection Behaviors, and Physical Activity. Preventing Chronic Diseases. Online Aug:9:E143.
  29. Handoko H., Box N.F. and Walker G.J. (2012) Modeling epidermal melanoma in mice: moving into new realms but with unexpected complexities. Journal of Investigative Dermatology 132(9):2299-2302.
  30. Terzian T. and Box N.F. (2013) Genetics of ribosomal proteins: “curiouser and curiouser”. PLOS Genetics epub January 31, 2013.
  31. Box, N.F., Vukmer, T.O., Terzian, T. (2013) Targeting p53 in melanoma. Pigment Cell and Melanoma Research, Accepted July 28th.
  32. Zeron-Medina, J., Wang, X., Repapi, E., Campbell, M.R., Su, D., Castro-Giner, F.C., Davies, B. Peterse, E.F.P., Sacilotto, N., Walker, G.J., Terzian, T., Tomlinson, I.P., Box, N.F., Meinshausen, N., De Val, S. Bell, D.A. and Bond G. (2013) A Polymorphic p53 Enhancer in the KIT Ligand Oncogene Influences Cancer Risk and Has Undergone Natural Selection. Cell Publication date: October 10th.
  33. Wallace, M., Box N.F., Bond G. (2014) A regulatory SNP links IRF4 to MITF and pigmentation. Pigment Cell and Melanoma Research, Accepted.