Kenneth H. Kraemer, M.D.
Laboratory of Cancer Biology and Genetics
Building 37, Room 4002
Bethesda, MD 20892
DNA Repair in Human Cancer-Prone Genetic Diseases
We are investigating the role of DNA repair in prevention of cancer and in human development. The approach involves integrated clinical, molecular, and translational investigations of disorders with defective DNA repair. Current studies are focusing on two rare genetic diseases: xeroderma pigmentosum (XP) a cancer-prone genetic disease with cellular hypersensitivity to ultraviolet radiation (UV) and defective DNA repair and trichothiodystrophy (TTD) a disorder with developmental abnormalities and defects in some of the same genes as XP without increased cancer risk.
The long-term goals are to: 1) define the molecular defects in these diseases, 2) characterize their clinical abnormalities and extent of phenotypic heterogeneity, 3) correlate the molecular defects with clinical abnormalities, 4) assess the altered molecular function, 5) identify and characterize the underlying mechanisms (pathophysiology) and how they lead to clinical disease, and 6) influence these processes by exploring methods of cancer prevention.
Collaborators on our research include Margaret Tucker, Human Genetics Program, Division of Cancer Epidemiology and Genetics, NCI; Brian Brooks, National Eye Institute (NEI); and Carmen Brewer, National Institute on Deafness and Other Communication Disorders (NIDCD).
Kuschal C, Botta E, Orioli D, Digiovanna JJ, Seneca S, Keymolen K, Tamura D, Heller E, Khan SG, Caligiuri G, Lanzafame M, Nardo T, Ricotti R, Peverali FA, Stephens R, Zhao Y, Lehmann AR, Baranello L, Levens D, Kraemer KH, Stefanini M. GTF2E2 Mutations Destabilize the General Transcription Factor Complex TFIIE in Individuals with DNA Repair-Proficient Trichothiodystrophy. Am J Hum Genet. 2016;98(4):627-42.
Heller ER, Khan SG, Kuschal C, Tamura D, DiGiovanna JJ, Kraemer KH. Mutations in the TTDN1 gene are associated with a distinct trichothiodystrophy phenotype. J Invest Dermatol. 2015;135(3):734-741.
Kuschal C, DiGiovanna JJ, Khan SG, Gatti RA, Kraemer KH. Repair of UV photolesions in xeroderma pigmentosum group C cells induced by translational readthrough of premature termination codons. Proc Natl Acad Sci U S A. 2013;110(48):19483-8.
Masaki T, Wang Y, DiGiovanna JJ, Khan SG, Raffeld M, Beltaifa S, Hornyak TJ, Darling TN, Lee CC, Kraemer KH. High frequency of PTEN mutations in nevi and melanomas from xeroderma pigmentosum patients. Pigment Cell Melanoma Res. 2014;27(3):454-64.
Bradford PT, Goldstein AM, Tamura D, Khan SG, Ueda T, Boyle J, Oh KS, Imoto K, Inui H, Moriwaki S, Emmert S, Pike KM, Raziuddin A, Plona TM, DiGiovanna JJ, Tucker MA, Kraemer KH. Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair. J Med Genet. 2011;48(3):168-76.
Related Scientific Focus Areas
Genetics and Genomics
Molecular Biology and Biochemistry
This page was last updated on September 12th, 2019