Northwestern University Feinberg School of Medicine

Duncan Lab

Research

We are grateful to the sponsors of our research. Funded research projects in the Duncan Lab include:

Current Projects

Homeostatic to reactive hyaluronan matrices in ovarian reproductive aging

The female reproductive system ages decades prior to other organs and results in infertility, miscarriages, and birth defects - with such adverse consequences of particular concern as women worldwide are delaying childbearing. We recently identified fibrosis and inflammation as a hallmark of the aging ovarian microenvironment in which eggs grow and develop, and in this project we seek to investigate the underlying mechanism to ultimately counteract this phenomenon and improve reproductive longevity and outcomes. We will test the hypothesis that age-associated loss and fragmentation of a key extracellular matrix molecule (hyaluronan) in the mammalian ovary converts the microenvironment into a reactive matrix that drives fibrosis and inflammation. This is a joint project with Dr. Michele Pritchard and Dr. Mary Ellen Pavone (R01HD093726).

Radiation therapy-induced cellular senescence and extra-follicular ovarian environment

Radiation is one of the most effective therapies to eliminate unwanted cells, such as cancer cells, but it can simultaneously damage non-targeted tissues resulting in medically-induced complications. The ovary – and particularly the gametes within it - is highly radiosensitive, and thus, premature reproductive aging due to follicle loss is a potential unintended and devastating outcome of radiation treatment. Here we will investigate how radiation therapy affects the extra-follicular ovarian microenvironment, testing the novel hypothesis that radiation-driven cellular senescence in the stroma is a prime mechanism underlying compromised reproductive function. This work is a pilot project within the Center for Reproductive Health After Disease (P50 HD076188, Center Director: T.K. Woodruff).

Inflammatory Biomarkers of Female Reproductive Aging and Potential

In this project, we are validating whether a conserved inflammatory cytokine profile increases with age in human cumulus cells and whether it directly correlates with embryo outcomes in ART procedures. If successful, these studies will define a non-invasive reproductive aging signature that could provide a clinically relevant non-invasive readout of embryo potential. Such knowledge will thus have the dual benefit of improving reproductive health and offspring outcomes in women of advanced reproductive age. This work is a joint project with Dr. Mary Ellen Pavone and is funded through a Friends of Prentice grant through the Northwestern Memorial Foundation.

Sperm Safes: Maximizing the preservation and recovery of limited numbers of male germ cells

The goal of this work is to use a mouse model to test the efficacy and safety of using novel biological platforms to cryopreserve and recover small numbers of mammalian sperm to restore fertility. This work is funded by a Daniel Manela Research Grant through the Pediatric Oncofertility Research Foundation. The goal of this work is to use a mouse model to test the efficacy and safety of using novel biological platforms to cryopreserve and recover small numbers of mammalian sperm to restore fertility. This work is funded by a Daniel Manela Research Grant through the Pediatric Oncofertility Research Foundation.

Collaborators

Jennifer Gerton, PhD (Stowers Institute for Medical Research)

Jessica Hornick, PhD (Northwestern University)

Bruce Kimler, PhD (University of Kansas Medical Center)

T. Rajendra Kumar, PhD (University of Colorado Denver)

Mary Ellen Pavone, MD, MSCI (Northwestern University)

Michele Pritchard, PhD (University of Kansas Medical Center)

Jeffrey Savas, PhD (Northwestern University)

Chad Slawson, PhD (University of Kansas Medical Center)

Sadie Wignall, PhD (Northwestern University)

Teresa Woodruff, PhD (Northwestern University)

Publications

For a list of publications from this lab, see: