Kenneth H. Kraemer, M.D.
We are investigating the role of DNA repair in prevention of cancer and in human development. We perform clinical, molecular, and translational investigations of two rare genetic disorders with defective DNA repair: xeroderma pigmentosum (XP) with clinical and cellular hypersensitivity to ultraviolet radiation and a 10,000-fold increased risk of skin cancer and trichothiodystrophy, a disorder with developmental abnormalities and defects in some of the same genes as XP without increased cancer risk. We recently found that the molecular changes in skin melanomas from the XP patients were closely related to sun exposure and different from the general population.
DNA repair, UV damage, skin cancer, primary melanoma, xeroderma pigmentosum, trichothiodystrophy
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).
Selected Recent Publications
GTF2E2 mutations destabilizing the general transcription factor complex TFIIE in two individuals with DNA repair proficient trichothiodystrophy.American Journal of Human Genetics. 98: 627-642, 2016. [ Journal Article ]
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. 110: 19483-8, 2013. [ Journal Article ]
- Journal of Investigative Dermatology . 136: 734 - 741, 2015. [ Journal Article ]
- Pigment Cell and Melanoma Research . 27: 454-464, 2014. [ Journal Article ]
Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair.J. Med. Genet. 48: 168-76, 2011. [ Journal Article ]
Dr. Kraemer received his M.D. from Tufts Medical School and is board certified in dermatology and internal medicine. He has a longstanding interest in human cancer-prone genetic diseases and DNA repair. His studies focus on molecular, cellular, and clinical features of diseases including xeroderma pigmentosum and familial melanoma. He is a member of the American Society for Clinical Investigation and has received awards from the Society for Investigative Dermatology and the U.S. Public Health Service.
|Laila Al-Eryani Ph.D.||Postdoctoral Fellow (Visiting)|
|John J. DiGiovanna M.D.||Senior Research Physician|
|Sikandar G. Khan, Ph.D.||Staff Scientist|
|Melissa Levoska||Special Volunteer|
|Nathaniel Patel||Special Volunteer|
|Jennifer M. Pugh||Postbaccalaureate Fellow|
|Grant Randall||MRSP Fellow|
|Deborah E. Tamura R.N., M.S.||Senior Clinical Research Nurse|
|Xiaoling (Charlene) Zhou Ph.D.||Biologist|