Dolores Lamb, PhD
Director, Developmental Biology; Co-Director, Research Learning Center; Professor of Surgery, University of Missouri-Kansas City School of Medicine
Full BiographyDolores J. Lamb, PhD, Urology, received a $2,892,915 Research Project Grant (R01) from the National Institute of Health’s National Cancer Institute (NCI).
The grant is for Dr. Lamb’s study “DNA Repair Deficiencies in Infertile Men and Cancer Risk” for a project period of Aug. 1, 2024-April 30, 2029 (Project Number: 7R01CA290670-02). The study will define the molecular links between male infertility and their increased risk of serious diseases, such as cancer.
As Dr. Lamb explains, there is a need to identify the causes of the most severe form of male infertility, non-obstructive azoospermia (NOA), where there is spermatogenic failure resulting in an ejaculate with no sperm.
“NOA men have an increased risk of serious diseases, such as cancer, when compared with fertile men or men with sperm in their ejaculates. However, the common link between their infertility and their increased disease risk has remained elusive,” explains Dr. Lamb.
The Lamb lab works on the molecular basis of NOA, specifically defects in DNA/mismatch repair proteins. She is using the results of previous research to focus her attention on defining the cancer risks of men with NOA and to look for common genetic/epigenetic links between men’s infertility and their health risk.
The study will look into the mismatch repair (MMR) proteins and MutS homolog 5 (MSH5), which are involved in DNA repair and meiotic recombination, a process that occurs during meiosis when homologous chromosomes in a cell exchange DNA segments with each other. MMR-deficient cells often have many DNA mutations that can lead to cancer.
For this study, Dr. Lamb and her team will use databases of expertly characterized NOA men from three institutions which includes ~14,200 NOA/severely oligozoospermic men (men with low sperm count) and more than 56,600 infertile men. Their profiles will be matched to the national Virtual Pooled Cancer Registry in the U.S. and the Canadian Cancer Registry.
“We will test the hypothesis that the decreased mismatch repair and/or MSH5 expression in a subset of infertile men leads not only to decreased genetic stability, impaired DNA break, and defective homologous recombination but also leads to the development of malignancies and NOA,” said Dr. Lamb.
As Dr. Lamb explains, these investigations are important because there are associated health issues for azoospermic men - those whose ejaculate contains no sperm - but frequently infertile men are never evaluated when couples are treated by in vitro fertilization and intracytoplasmic sperm injection (ICSI).
“(In the future) these men could be advised of their potential health risks associated with their infertility. They can be closely followed for cancer development,” said Dr. Lamb. “Earlier intervention may improve their outcomes.”
Co-investigators on the study include Keith Jarvi, MD, Ethan Grober, MD, Kirk Lo, MD, and Christopher Wallis, MD, all from Mount Sinai Hospital in Toronto, Mark Sigman, MD, and Gabriella Avellino, MD, from Rhode Island Hospital, Andrew Vickers, PhD (Memorial Sloan Kettering Cancer Center), Peter Schlegel, MD (New York Men’s Health Medical), James Kashanian, MD, Marc Goldstein, MD, Kevin Kensler, ScD, from Weill Cornell Medicine.
The contents are those of the investigator and do not necessarily represent the official views of, nor an endorsement, by NIH, or the U.S. Government.