University of Chicago researchers receive new supplemental awards to counter gender bias in NIH-funded research

Investment sets the stage for a transformative shift in science

September 2014

Five University of Chicago research projects are receiving supplemental funding from the National Institutes of Health (NIH) as part of a $10.1 million investment to explore the effects of gender in preclinical and clinical studies. A total of 82 supplemental grants were awarded Tuesday.

This investment encourages researchers to study both females and males, and is a catalyst for considering sex as a fundamental variable in scientific and medical research. The current overreliance on male subjects in preclinical research can obscure important findings that could guide later human studies. This progressive approach will result in greater awareness of the need to study both sexes, demonstrate how research can incorporate sex and reinforce the value of taking gender into account as these studies yield results.

"This focus on sex-differences at NIH is very important as many human traits, including diseases, display sex-biased characteristics," said Barbara Stranger, PhD, assistant professor in the Department of Medicine at the University of Chicago. "It is important to characterize these differences in detail and to understand what underlies them."

The awards announced Tuesday are the latest round of funding in a program described in a May 2014 Nature commentary by NIH leaders. In the op-ed piece, NIH officials said future grant applicants will be required to address the influence gender in the design and analysis of biomedical research with animals and cells.

"Identifying sex-differences, or proving that an observation is equally valid in both males and females, is critical to understanding biological systems and will go a long way to improving our ability to translate our findings to humans," said Abraham Palmer, PhD, associate professor of human genetics at the University of Chicago.

The projects funded at the University of Chicago include:

• The Genetic Basis of Cross-Tissue Protein Expression Variability in Humans
• Principal Investigator: Barbara Stranger, PhD
• This research project studies how genetic differences between individuals affects the variability of hundreds of important proteins in human tissues. How these genetic differences contribute to variation in higher order traits, including susceptibility to disease, will be analyzed. The supplement will allow researchers to study 100 additional proteins and enables a focus on proteins that play a role in sex differences.
• Systems Genetic Analysis of Methamphetamines Motivational Effects in a Mouse Advanced Intercross Line
• Principal Investigator: Abraham Palmer, PhD
• Using behavioral models, molecular genetic techniques and statistical methods, this research project identifies genes in mice that are linked to liking or disliking the effects of certain drugs over others. The supplement will be used to increase the sample size of animals in the parent grant and follow up on data suggesting females show greater sensitivity to various aspects of methamphetamines.
• Conte Center for Computational Systems Genomics of Neuropsychiatric Phenotypes
• Principal Investigator: Andrey Rzhetsky, PhD
• Co-Investigators: Barbara Stranger, PhD, Lea Davis, PhD 
• This research project uses computational modeling to identify new ways to link genetic and environment factors with mental health conditions. The supplement will broaden modeling techniques to include those that assess sex differences in genetic risk for various neuropsychiatric conditions. Those conditions include anxiety, schizophrenia and depression.
• PAAR-Pharmacogenomics of Anticancer Agents Research Group
• Principal Investigators: Mark Ratain, MD, Nancy Cox, PhD, Eileen Dolan, MD
• Co-Investigator: Barbara Stranger, PhD
• This research project studies variability in drug response to cancer therapies by describing genetic variants involved in differences toward drug actions and side effects. The project aims to leverage genomics toward creating individualized therapies that will improve efficacy and decrease adverse reaction to cancer treatment. The supplement will characterize sex effects on these genetic variations toward drug effects.
• Harnessing GTEx to Create Transcriptome Knowledge and Inform Disease Biology
• Principal Investigators: Nancy Cox, PhD, Dan Nicolae, PhD
• Co-Investigator: Barbara Stranger, PhD
• This research project will enhance understanding of the genetic architecture of complex human traits, including that of common diseases, by studying how genetic differences affect gene expression variability within and between tissues. The supplement will fund additional analyses to uncover differences between sexes in the regulation of gene expression levels.

Two of the new University of Chicago Medicine awards, led by Stranger and Nancy Cox, PhD, Professor and Section Chief of Genetic Medicine, are supplements to existing grants from the NIH Common Fund, which identifies and funds areas of biomedical science to create new fields of research and to develop large-scale public resources that benefit the research community. Knowledge gained from these supplements is expected to impact research across a variety of scientific disciplines.

"This funding strategy demonstrates our commitment to moving the needle toward better health for all Americans, while helping grow our knowledge base for both sexes and building research infrastructure to aid future studies," said Janine Austin Clayton, MD, the NIH's associate director for women's health research. "The scientists receiving these awards have approached their research questions with fresh thinking, and are looking for innovation and discovery through a new lens."

About the Office of Research on Women's Health: The NIH Office of Research on Women's Health (ORWH) promotes research that considers sex and gender to provide critical insights essential to understanding women's health. ORWH also works to ensure that NIH clinical research takes sex/gender and race/ethnicity into account across the lifespan. ORWH establishes the NIH research agenda for women's health, co-funds research in partnership with NIH Institutes and Centers, and advances women in biomedical careers and women's health researchers. Learn more about ORWH.

About the Common Fund: The NIH Common Fund encourages collaboration and supports a series of exceptionally high-impact, trans-NIH programs. Common Fund programs are designed to pursue major opportunities and gaps in biomedical research that no single NIH Institute could tackle alone, but that the agency as a whole can address to make the biggest impact possible on the progress of medical research. Learn more about the NIH Common Fund.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. Learn more about NIH and its programs.