Miriam Sander

Xeroderma pigmentosum and other diseases of human premature aging and DNA repair: molecules to patients.

A workshop(1) to share, consider and discuss the latest developments in understanding xeroderma pigmentosum and other human diseases caused by defects in nucleotide excision repair (NER) of DNA damage was held on September 21-24, 2010 in Virginia. It was attended by approximately 100 researchers and clinicians, as well as several patients and representatives of patient support groups. This was the third in a series of workshops with similar design and goals: to emphasize discussion and interaction among participants as well as open exchange of information and ideas. The participation of patients, their parents and physicians was an important feature of this and the preceding two workshops. Topics discussed included the natural history and clinical features of the diseases, clinical and laboratory diagnosis of these rare diseases, therapeutic strategies, mouse models of neurodegeneration, molecular analysis of accelerated aging, impact of transcriptional defects and mitochondrial dysfunction on neurodegeneration, and biochemical insights into mechanisms of NER and base excision repair.

New areas of focus at workshop on human diseases involving DNA repair deficiency and premature aging.

Researchers and clinicians interested in human diseases of DNA repair deficiency and premature aging gathered at the National Conference Center in Lansdowne, Virginia on 5-8 September 2006 to attend a workshop co-organized by Vilhelm Bohr (National Institute of Aging) and Kenneth Kraemer (National Cancer Institute). An important feature of this workshop was the participation of representatives from xeroderma pigmentosum (XP), Cockayne Syndrome (CS) and trichothiodystrophy (TTD) family support groups. Studies presented at the workshop described important new insights into the phenotypic complexity of XP, CS and TTD, renewed focus on the neurological manifestations of each of these diseases, as well as keen interest in the role of oxidative stress and mitochondrial dysfunction in neurodegenerative processes and normal and/or premature aging. This workshop report summarizes some of the presentations and outcomes of the workshop.

Bloom's syndrome workshop focuses on the functional specificities of RecQ helicases.

Human cells express five DNA helicases that are paralogs of Escherichia coli RecQ and which constitute the family of human RecQ helicases. Disease-causing mutations in three of these five human DNA helicases, BLM, WRN, and RECQL4, cause rare severe human genetic diseases with distinct clinical phenotypes characterized by developmental defects, skin abnormalities, genomic instability, and cancer susceptibility. Although biochemical and genetic evidence support roles for all five human RecQ helicases in DNA replication, DNA recombination, and the biological responses to DNA damage, many questions concerning the various functions of the human RecQ helicases remain unanswered. Researchers investigating human and non-human RecQ helicases held a workshop on May 27-28, 2008, at the University of Chicago Gleacher Center, during which they shared insights, discussed recent progress in understanding the biochemistry, biology, and genetics of the RecQ helicases, and developed research strategies that might lead to therapeutic approaches to the human diseases that result from mutations in RecQ helicase genes. Some workshop sessions were held jointly with members of a recently formed advocacy and support group for persons with Blooms syndrome and their families. This report describes the outcomes and main discussion points of the workshop.

The 20th Aspen Cancer Conference: Mechanisms of Toxicity, Carcinogenesis, Cancer Prevention, and Cancer Therapy 2005.

The 20th Aspen Cancer Conference on Mechanisms of Toxicity, Carcinogenesis, Cancer Prevention, and Cancer Therapy was held from July 24 to 28, 2005 in Aspen, Colorado. Recognizing the importance of a 20-year history of excellence, the 2005 Aspen Cancer Conference included an extended scientific program as well as several special presentations and events. The scientific program, developed by a Scientific Advisory Committee co-chaired by Benjamin F. Trump (AMC Cancer Center) and Curtis C. Harris (National Cancer Institute, NIH), featured an extra day of seminars by former Aspen Cancer Conference Keynote Speakers. The returning keynote speakers included J. Michael Bishop, Douglas Hanahan, Thea Tlsty, Tony Hunter, and Scott Lowe. In a special public Conference Session held at the Aspen Institute, former NIH director Harold Varmus lectured on Oncogenes and the Future of Cancer Therapy, Ms. Karen Allred presented a piano recital, and former Ambassador to the Netherlands K. Terry Dornbush described A Survivor’s Story, cancer from the perspective of a two-time prostate cancer survivor. Other special programming in acknowledgement of the 20th year of the Aspen Cancer Conference included a whole day devoted to drug discovery with presentations from Cecil Pickett (Schering-Plough Research Institute), James Doroshow (National Cancer Institute), and Carl Barrett (Novartis) a review of the history of the Aspen Cancer Conference in the context of the history of Aspen, Colorado presented by Donald King (National Library of Medicine), and an awards ceremony honoring sustained contribution to the Aspen Cancer Conference by Theodore Puck, Benjamin J. Trump, and Donald King. The goals of the Aspen Cancer Conference are: to understand the mechanisms of toxicity and carcinogenesis, to understand and minimize cancer risk, to assess the public-health impact of cancer risk, and to develop the scientific basis for improving the diagnosis, prevention, and treatment of toxic and neoplastic disease. The Aspen Cancer Conference fosters intense interaction, discussion, and collaboration among key stakeholders in cancer research. One of the strengths of the Conference is the sustained participation in and support of the Conference by leaders in cancer research from government, academic, and industry sectors. Because of its unusual qualities, the Aspen Cancer Conference provides an environment that is uniquely conducive to generating novel insights related to current issues in cancer prevention, intervention, and therapy. The 20th Aspen Cancer Conference included seven Conference Sessions, a Poster Session by Aspen Cancer Conference Fellows and numerous informal discussions. Session topics included Progress in Drug Development, Metastasis, Inflammation and Cancer, Stress and Cancer, Risk Assessment, Technology Innovations and Apoptosis. At the close of the 2005 Conference, the Scientific Advisory Committee met to select topics for the 21st Aspen Cancer Conference which will held from July 16 to 18, 2006. This meeting summary concisely describes the content of each of the Conference Sessions and the scientific portions of the Special Sessions.

Seventeenth Aspen Cancer Conference: mechanisms of toxicity, carcinogenesis, cancer prevention, and cancer therapy†

INTRODUCTION The17 Aspen CancerConferenceon Mechanisms of Carcinogenesis, Cancer Prevention, and Cancer Therapy was held July 14–16, 2002 in Aspen, Colorado. The program of the conference was organized by a Scientific Advisory Committee cochaired by Benjamin F. Trump (AMC Cancer Center) and Curtis C. Harris (National Cancer Institute, NIH). The tradition of the Aspen Cancer Conference is to provide a forum for discussion of recent advances in understanding of fundamental mechanisms of toxicity and carcinogenesis. Representatives from government, academic, and industry research groups participate in the conference and bring their knowledge to bear on advancing the following goals: understanding the mechanisms of toxicity and carcinogenesis, understanding and minimizing cancer risk, assessing the public-health impact of cancer risk, and improving the ability of the biomedical community to diagnose, prevent, and treat toxic and neoplastic disease. The Aspen Cancer Conference fosters intense interaction, discussion, and collaboration among its participants, leading to new insights and understanding of carcinogenesis and related topics. The conference also focuses on new concepts and technologies. The 17 Aspen Cancer Conference included 10 conference sessions, a special lecture by Scott Lowe, a poster session by young investigators, and numerous informal discussions. The Scientific Advisory Committee also met to select topics for the 18 Aspen Cancer Conference, to be held in 2003. This meeting summary concisely describes the content of each of the conference sessions and the special lecture.

Great leaps forward: translesion synthesis gets unstalled

One important question facing the field of DNA repair is: how does the cell sense and respond to the presence of DNA damage? Many sessions at this meeting discussed the potential signalling cascades that might contribute to this poorly understood process. There are many possible players, including some or all of the following: the DNA lesion itself, ‘naked’ single-stranded DNA, stalled replication and transcription complexes, MMR proteins bound to DNA damage, futile DNA repair cycles, protein kinases including DNA-PK and ATM, and cell-cycle regulatory proteins including p53, p73 and p21. Modrich presented evidence that MMR proteins act at an early step in this process: both hMutSα and hMutLα are required for DNA-damage-dependent phosphorylation of p537xhMutSα- and hMutLα-dependent phosphorylation of p53 in response to DNA methylator damage. Duckett, D.R. et al. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 12384–12388Crossref | PubMed | Scopus (146)See all References7, and others have shown that hMutSα is required for the induction of apoptosis in response to certain alkylated DNA bases8xRole of DNA mismatch repair and p53 in signaling induction of apoptosis by alkylating agents. Hickman, M.J. and Samson, L.D. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 10764–10769Crossref | PubMed | Scopus (248)See all References8. Thus, eukaryotic MMR proteins might regulate directly or indirectly at least one branch of the DNA-damage-dependent signalling cascade. This is an important area for future studies and is likely to show significant progress between now and the next Mega-Meeting on DNA Repair and Mutagenesis.

The 23rd Aspen Cancer Conference: Mechanisms of Toxicity, Carcinaogenesis, Cancer Prevention and Cancer Therapy 2008

The 23rd Aspen Cancer Conference on Mechanisms of Toxicity, Carcinogenesis, Cancer Prevention and Cancer Therapy was held July 20–22, 2008 in Aspen, Colorado. The goals of the Aspen Cancer Conference are to understand the mechanisms of toxicity and carcinogenesis, to understand and minimize cancer risk, to assess the public health impact of cancer risk, and to develop the scientific basis for improving the diagnosis, prevention and treatment of toxic and neoplastic disease. The Aspen Cancer Conference fosters intense interaction, discussion and collaboration among key stakeholders in cancer research. One of the strengths of the conference is the sustained participation in and support of the conference by leaders in cancer research from government, academic and industry sectors. Because of its unusual qualities, the Aspen Cancer Conference provides an environment that is uniquely conducive to generating novel insights related to current issues in cancer prevention, intervention and therapy. The scientific program for the 23rd Aspen Cancer Conference included eight Conference Sessions, a Poster Session by Aspen Cancer Conference Fellows with presentation of the Theodore T. Puck Award, a Special Public Conference Session on Breast Cancer at the Aspen Institute, a Special Tribute to the late Benjamin F. Trump, presentation of the First Annual Benjamin F. Trump Lecture, and presentation of the First Benjamin F. Trump Fellowship Award. As a long standing tradition at the Aspen Cancer Conference, conference sessions allotted equal time for slide presentations and open discussion. Session topics in the 23rd Aspen Cancer Conference were: Metabolism and Obesity in Cancer, Personalized Oncology, Cancer Genomics, Hypoxia, Senescence and Cancer, Immunology, Companion Animals in Oncology and Centrosomes, Chromosomes and Nuclear Architecture. At the close of the Conference, the Scientific Advisory Committee, chaired by Curtis C. Harris, met to select topics for the 24th Aspen Cancer Conference. This meeting summary concisely describes the content of each of the Conference Sessions.