Project One

Transgenerational animal models of nutritional impact on cancer predisposition

Project Leader
Dr. Kelle H. Moley, James P. Crane Professor in Obstetrics and Gynecology, Division of Reproductive Endocrinology; Professor, Cell Biology and Physiology; Vice Chair and Director, Basic Science Research in Obstetrics and Gynecology

Collaborators
Dr. Adam S. Kibel, Professor of Surgery, Harvard Medical School; Chief of Urology, Brigham and Women's Hospital; and Chief of Urology, Dana Farber Cancer Institute

Dr. Jason Weber, Associate Professor of Medicine, Section of Molecular Oncology

Project Summary
Dr. Moley is looking at the effect of maternal high-fat diet and changes in metabolic bioenergetics on prostate gland development and susceptibility to prostate cancer in male offspring. She will address epigenetic changes that arise among offspring of obese females, leading to abnormal expression of key genes involved in the development of the prostate gland, which predispose the offspring to develop cancer. Dr. Moley’s findings will be positioned to inform molding of cancer in populations as implemented in Project Four.

Project Aims

  1. Examine prostate gland development and imprinted gene expression in control versus high-fat fed offspring, from mothers given a high-fat diet one month prior to conception and throughout pregnancy.
  2. Examine the incidence and timing of tumor development in offspring of control versus high-fat fed mothers by administration of diethylstilbestrol (DES) to neonatal male mice on postnatal days 1-5.
  3. Examine the effects of a high-fat fed diet on tumor development in an established model for prostate cancers.