Kenneth H. Kraemer, M.D.

Kenneth H. Kraemer received his M.D. degree from Tufts Medical School and is Board Certified in Dermatology and in Internal Medicine. He has a long-standing 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. Dr. Kraemer is co-organizer of the NIH DNA Repair Interest Group.

RESEARCH

DNA Repair in Human Diseases:

Human cancer prone genetic diseases are being studied to identify groups of people with an increased susceptibility to environmental agents. Present emphasis is on the skin cancer-prone disease, xeroderma pigmentosum (XP) and on dysplastic nevus syndrome (DNS) of familial melanoma. We are attempting to: 1) understand the molecular basis of the cellular hypersensitivity of these diseases, 2) correlate cellular hypersensitivity with clinical abnormalities, 3) determine the degree of genetic heterogeneity within such groups, and 4) explore methods of cancer prevention.

We developed plasmid assays to measure DNA repair and mutagenesis at the molecular level in human cells. We found that introduction of cloned DNA repair genes substantially corrected the UV mutagenic defect in XP-D and XP-A cells.  We are currently identifying mutations in the DNA repair genes of XP patients and attempting to correlate the molecular defects with their clinical features. Studies of lymphoblastoid cells from normal donors showed increased plasmid UV mutability with increasing donor age suggesting that aging is associated with decreasing ability to repair DNA damage. Lymphoblastoid cell lines from DNS patients with melanoma were found to have abnormally elevated mutability of UV-treated plasmids, a possible cellular marker for this genetic disorder.

Clinical studies of carcinogenesis and chemporevention: Chemoprevention of skin cancer in XP with oral 13-cis retinoic acid (RA) was studied. High dose (2 mg/kg/da) 13-cis RA was effective in preventing skin cancers but very toxic, and low dose (0.5 mg/kg/da) drug gave variable response in different patients ranging from almost complete tumor prevention to no beneficial effect. Despite extensive sun protection, XP patients had normal levels of serum vitamin D indicating an adequate dietary intake of vitamin D. Therapeutic injection of intralesional interferon resulted in marked clearing of multiple melanoma in-situ lesions in one XP patient. The anatomic location of skin cancers in XP patients indicates that although UV exposure causes both melanoma and non-melanoma cancer, the mechanism of skin cancer induction is different for each type of cancer.

1. Moriwaki, S-I, Ray, S., Tarone, R.E., Kraemer, K.H, and Grossman, L.: The effect of donor age on the processing of UV- damaged DNA by cultured human cells: Reduced DNA repair capacity and increased DNA mutability. Mutat Res DNA Repair 364: 117-123, 1996
2. Moriwaki, S-I., Stefanini, M., Lehmann, A.R., Hoeijmakers, J.H.J., Robbins,J.H., Rapin, I., Botta, E., Tanganelli, B.,Vermeulen, W., Broughton, B.C., and Kraemer, K.H.: DNA repair and ultraviolet mutagenesis in cells from a new patient with xeroderma pigmentosum group G and Cockayne syndrome resemble xeroderma pigmentosum cells. J Invest Dermatol 107: 647-653, 1996.
3. Kraemer, K.H.: Sunlight and skin cancer: Another link revealed. Proc Natl Acad Sci USA 94: 11-14, 1997.
4. Bootsma, D., Kraemer, K.H., Cleaver, J.E., and Hoeijmakers, J.H.J.: Nucleotide excision repair syndromes: xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy.  In Vogelstein, B. and Kinzler, K.  Eds, The Genetic Basis of Human Cancer,  1997, McGraw Hill pp 245-274.
5. Sollitto, R.B., Kraemer, K.H., DiGiovanna, J.J.: Normal vitamin D levels can be maintained despite rigorous photoprotection: six years experience with xeroderma pigmentosum. J Am Acad Dermatol 37: 942-947, 1997.
6. Okinaka, R.T., Perez-Castro, A.V., Sena, A., Laubscher, K., Strniste, G.F., Park, M.S., Hernandea, R., MacInnes, M.A., and Kraemer, K.H.: Heritable genetic alterations in a xeroderma pigmentosum group G/Cockayne syndrome pedigree. Mut Res 385: 107-114, 1997.
7. Moriwaki, S-I., Tarone, R.E. , Tucker, M.A., Goldstein, A.M. and Kraemer, K.H.: Hypermutability of ultraviolet treated plasmids in dysplastic nevus/ familial melanoma cell lines Cancer Res 57: 4637-4641, 1997.
8. DiGiovanna, J.J., Patronis, N., Katz, D., Abangan, D., and Kraemer, K.H.: Spinal cord astrocytoma in a patient with xeroderma pigmentosum: 9-year survival with radiation and isotretinoin therapy. J Cut Med Surg 2:153-158, 1998.

 

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