Twenty-Ninth AACR Award for Outstanding Achievement in Cancer Research
Victor E. Velculescu, M.D., Ph.D.
Associate Professor of Oncology and Co-Director of Cancer Biology
The Sidney Kimmel Comprehensive
Cancer Center at Johns Hopkins
Baltimore, MD
Through the generous contribution of an anonymous donor, the AACR established this Award in 1979 to recognize a young investigator for meritorious achievement in cancer research. In accordance with the wishes of the donor, the recipient must be no more than 40 years of age by the time the Award is received.
Dr. Victor E. Velculescu is recognized for his fundamental impact on the field of cancer genetics by pioneering a series of cutting edge technologies that have removed the usual impediments to genetic analysis of human disease. He has applied these approaches to make critical discoveries that have major implications for the understanding and clinical management of cancer.
Dr. Velculescu is responsible for developing Serial Analysis of Gene Expression (SAGE), a gene expression technology that allows for measurements of quantitative gene activity without prior knowledge of the genome sequence. Consequently, it is the method of choice for characterizing any genome in an unbiased manner, and is particularly useful for those genomes which are highly rearranged, including cancer cells or the genomes of a species with no sequence information. Dr. Velculescu has applied this approach to obtain the first "transcriptome" of a eukaryotic cell and to provide the first insights into gene expression patterns of human cancer cells.
His second innovation is the development of Digital Karyotyping which allows for quantitatively characterizing amplification/loss of genes at the DNA levels in an unbiased manner and at high resolution. Dr. Velculescu has used this technology to identify copy number alterations that underlie chemotherapy-resistant metastatic colorectal cancer.
Finally, through his work in large-scale sequencing of cancer genomes, he identified alterations in the PIK3CA gene in a large fraction of colorectal, breast, brain, and stomach cancers, making this one of the most highly mutated genes ever identified in human cancer. He showed that mutations in this gene are crucial for tumor growth and invasion and that cancers with such mutations are especially sensitive to PI3K inhibitors.
These results have spurred the interest of pharmaceutical companies and he has worked several academic and industrial groups to develop novel PI3K pathway inhibitors for clinical use. His recent publications describing a genome-wide sequencing approach to breast, colorectal, and pancreatic cancers and glioblastoma multiforme have been landmarks in the field, identifying a treasure trove of new therapeutic and diagnostic targets. The integration of multiple genome-wide mutational data sets has now become the standard of genetic analyses in human cancer and has provided insights about important mechanistic features and pathways that underlie these tumors. Importantly, this work is spurring on similar studies nationally and internationally in the Cancer Genome Atlas Project (TCGA) and the International Cancer Genome Consortium (ICGC).
Third Annual AACR Award for Outstanding Achievement in Chemistry in Cancer Research
F. Peter Guengerich, Ph.D.
Harry Pearson Broquist Professor of Biochemistry and
Director of the Center in Molecular Toxicology
Vanderbilt University School of Medicine
Nashville, TN
The AACR and its Chemistry in Cancer Research Working Group established this Award in 2007 to recognize the importance of chemistry to advancements in cancer research. The Award will be given for outstanding, novel, and significant chemistry research, which has led to important contributions to the fields of basic cancer research, translational cancer research, cancer diagnosis, the prevention of cancer, or the treatment of patients with cancer.
Dr. Guengerich is honored for his seminal studies on the role of individual human cytochrome P450 in the metabolic activation of carcinogens to intermediates that mutate genes, which stand as a landmark in research on mechanisms and prevention of cancer.
His prolific contributions to the literature, with over 550 original refereed contributions in top journals, particularly in the area of cytochrome P450 enzymes, stand as a monumental body of superb work forming the basis for much of our understanding of how carcinogens are metabolized to intermediates that cause cancer through DNA interactions. This work began with the first isolations of human cytochrome P450 in the 1970s and has proceeded unabated through detailed mechanistic studies of carcinogen and drug metabolism.
In addition to these seminal studies, Dr. Guengerich has also made major advances in the understanding of the reactions of metabolically activated carcinogens with DNA to form adducts, defining the details of mechanisms of several classes of carcinogens including the arylamines, vinyl halides, and dihaloalkanes. These studies take advantage of ingenuous labeling schemes and other novel tools to define these chemical mechanisms.
His studies on carcinogen metabolic activation and DNA adduct chemistry naturally lead to the question of the mechanisms by which DNA adducts produce mutations, the subject of his award lecture. Approaches to this problem clearly demonstrate Professor Guengerich's superb ability to apply a wide variety of chemical and physical methods including oligonucleotide synthesis, rapid kinetics methods, X-ray crystallography, and mass spectrometry.
Eighteenth Annual AACR-American Cancer Society Award for Research Excellence in Cancer Epidemiology and Prevention
John D. Potter, M.D., Ph.D.
Member and Senior Advisor
Fred Hutchinson Cancer Research Center
and Professor of Epidemiology
University of Washington
Seattle, WA
The AACR and the American Cancer Society established this Award in 1992 to honor outstanding research accomplishments in the fields of cancer epidemiology, biomarkers, and prevention.
Dr. John D. Potter is honored for contributing in a visionary and major way to current understanding of the epidemiology and prevention of colorectal cancer. He has elucidated aspects of the roles of diet, exercise, hormones, and genetics in the etiology of this disease, with pioneering work in hormonal aspects and in the use of molecular biologic tools. His leadership of interdisciplinary collaborations has contributed to important progress in our understanding of the interplay between molecular and epidemiologic factors in the causation and prevention of this important disease.
Dr. Potter has significantly contributed to many topics related to cancer occurrence over the past 25 years, as evidenced by his extensive bibliography. His focus has been on the etiology and prevention of colorectal cancer, a disease that continues to be the source of substantial morbidity and mortality worldwide, especially in Western countries. As early as 1980 he proposed a role for sex hormones in the etiology of colorectal cancer, based on age and sex-specific incidence patterns. This was followed by more specific analytic epidemiology studies of reproductive and hormonal factors during the mid-1980s.
A major focus early in his career was on dietary factors in relation to cancers of the colon and rectum. This involved state-of-the-art case-control studies, and later, human feeding studies with biomarker outcomes. He is widely recognized from this work for establishing the consistency of evidence supporting a lower risk for colorectal and several other cancers with plant food consumption.
Dr. Potter and his colleague Marty Slattery were also leaders in a new research direction that is now a major aspect of molecular epidemiology: genetic susceptibility factors and colorectal cancer risk, as well as on the interaction of genetics (and epigenetics) with dietary and other exposures. Examples include the role of the NAT2 phenotype, smoking, and colorectal adenoma, and DNA methylation and repair abnormalities, folate consumption, and colorectal adenoma, to name just a few. His vision has provided leadership in the area of molecular epidemiology, using novel biologic tools to elucidate disease pathways, molecular classification of tumors and a transdisciplinary approach to cancer prevention.
Twelfth Annual AACR-Women in Cancer Research Charlotte Friend Memorial Lectureship
Jessica K. Tyler, Ph.D.
Associate Professor
Department of Biochemistry and Molecular Genetics
University of Colorado School of Medicine
Denver, CO
In 1998, the Charlotte Friend Memorial Lectureship was instituted in honor of Dr. Charlotte Friend with the intent to recognize an outstanding scientist who has not only made meritorious contributions in the field of cancer research but has also, either through leadership or by example, furthered the advancement of women in science.
Dr. Jessica K. Tyler has made fundamental contributions to our mechanistic understanding of how chromatin regulates gene expression, DNA repair and replication. These contributions include her demonstration that the removal of histones from regulatory regions of genes is essential for transcriptional activation while depositing histones onto these DNA regions is essential for transcriptional repression. This work also revealed that the only function of transcriptional activators in cells is to overcome the repressive effect of chromatin. As a postdoctoral fellow, Dr. Tyler discovered the highly conserved and most prominent histone chaperone, Asf1. Her subsequent high resolution crystal structure of Asf1 bound to histones H3/H4 was the first time that the histone units of chromatin had ever been seen in a structure outside of the nucleosome, and provided paradigm-shifting insight into how chromatin is formed and taken apart in the cell. Her studies of double-strand DNA repair have led to the demonstration that chromatin is dismantled to allow DNA to be repaired, while chromatin is rebuilt after repair.
Strikingly, this study found that repair of DNA per se is not sufficient for turning off the DNA damage cell cycle checkpoint, but instead that packaging the repaired DNA into chromatin is the elusive signal that indicates that DNA repair is complete. Dr. Tyler has recently discovered a new aging pathway and a novel approach to extend lifespans that is due to a specific epigenetic mark on the chromatin, and has revealed the mechanistic basis for the influence of this epigenetic mark on aging. She has also discovered that this epigenetic mark is present in human cells, and has identified the enzyme responsible for creating this mark as p300/CBP. Furthermore, this epigenetic mark is induced by DNA damage and is present at elevated levels in most types of tumors, where increased levels correlates with increasing tumor grade. In summary, Dr. Tyler's research has greatly advanced our understanding of some of the fundamental cellular processes that are central to cancer progression.
In addition, Dr. Tyler is an excellent role model for women scientists, particular those early-career investigators who are entering the field. Her rapid rise through the academic ranks serves as an example of the success that can be attained by all scientists, but particularly women who balance careers with family. She is the mother of four-year old triplets. Her generosity in mentoring is further evident through her organization of an event for female scientists to address challenges facing women scientists today.
Fourth Annual AACR-Minorities in Cancer Research Jane Cooke Wright Lectureship
Otis Webb Brawley, M.D.
Chief Medical Officer
Executive Vice President
American Cancer Society
Atlanta, GA
The AACR-Minorities in Cancer Research Jane Cooke Wright Lectureship was established in 2006 to give recognition to an outstanding scientist who has made meritorious contributions to the field of cancer research and who has, through leadership or by example, furthered the advancement of minority investigators in cancer research.
Dr. Otis W. Brawley is honored for his contributions to the field of cancer in the area of health disparities including screening, epidemiology, diagnosis, and treatment of hormonal cancers.
Dr. Brawley has been a strong advocate of "equal treatment yields equal outcome among equal patients." His work on the availability of the state-of-art health treatment to socioeconomically disadvantaged groups has changed attitudes of doctors treating these individuals. In addition, his commitment to health disparities has contributed to the development of numerous young scientists conducting research in this area. He has mentored many pre- and post doctoral fellows, as well as medical fellows in cancer research.
His initial suggestions of potential dietary agents for prostate cancer chemoprevention have led to clinical trials involving these agents. In addition, Dr. Brawley led the National Cancer Institute Prostate Cancer Prevention program.
Dr. Brawley's research was instrumental in establishing the importance of hormonal prevention strategies for prostate cancer. The results of the Finasteride Chemoprevention Trial, which he played an important role, demonstrated that inhibition of 5- alpha reductase was a important and valid target for prostate cancer risk reduction and treatment strategies.