RAising the Investment in Sex and gender Evidence (RAISE) is a partnership of FOCUS and Penn PROMOTES.
RAISE is a structural intervention that aims to 1) advance scientists working to close the sex and gender data gap, 2) achieve gender equity in the scientific workforce, and 3) incorporate the analysis of sex and gender differences into research programs throughout the University of Pennsylvania's biomedical schools. RAISE will award grant funding to biomedical school faculty to pursue new research or revisit earlier research findings, applying sex and gender-disaggregated data analysis.
NOW ACCEPTING PROPOSALS FOR THE 2025-26 RAISE GRANT CYCLE
Important Dates
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Applications Due: Saturday, March 1, 2025 by 11:59 PM
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Notice of Award: Tuesday, April 1, 2025
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RAISE Symposium (grantees present their proposals): Thursday, May 1, 2025
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Grant Start Date: Tuesday, July 1, 2025
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Grant End Date: Tuesday, June 30, 2026
This year, we are awarding two grants of up to $20,000.
The full RAISE grant guide is available below.
Please reach out to Bridget Dougherty (bridget.dougherty2@pennmedicine.upenn.edu) with any questions.
RAISE Research Directory
This directory houses PSOM research that addresses sex and/or gender differences and women's health across all scientific methods. Our goal is to capture a comprehensive catalog of the sex and gender research landscape at our institution and create a helpful reference and build community. If you would like to join the directory, please complete this brief form.
2024 RAISE Pilot Grant Recipients
Improving cardiovascular clinical trial representativeness among women
PIs: Rachel Kohn, MD, MSCE; Scott D. Halpern, MD, PhD
Women experience suboptimal treatment for, and greater mortality from cardiovascular diseases. This stems in part from underrepresentation of women in cardiovascular trials, limiting the generalizability of advancements to women. Stakeholders identified communication as a key factor for mitigating trial enrollment discomfort, and financial incentives reduce racial gaps in trial accrual. Key unanswered questions include (1) which behavioral economic (BE)-informed communication strategies reduce participation gaps, (2) whether these strategies produce adverse ethical effects, and (3) whether communication strategies and incentives work synergistically to promote RCT enrollment. Therefore, we propose tests of these key questions to improve cardiovascular RCT representativeness among women. In Aim 1, we will evaluate combinations of messaging frameworks and financial incentives to maximize cardiovascular trial enrollment among women. In Aim 2, we will evaluate undue (i.e., decreasing participants’ sensitivity to risk) and unjust inducements (i.e., more influence among poorer patients) for BE strategies among women. Using Amazon mechanical turk, we will recruit 250 participants. Participants will receive 10 of 48 possible versions containing a hypothetical cardiovascular trial prompt that only varies in messaging framework, financial incentive, and risk. Participants will provide their willingness to participate (WTP) in each scenario on a five-point Likert scale. We will test associations of BE strategy combinations with WTP. We will test associations of interaction terms between the risk variable and BE combinations with WTP (testing for undue inducement), and between annual income and financial incentive with WTP (testing for unjust inducement). We will use multivariable ordinal logistic regression for all analyses.
X-chromosome mediated mechanisms mediating sex-specific differences in Neonatal Lung Injury
PIs: Krithika Lingappan, MD, PhD, MS; Montserrat Anguera, PhD
Despite improved neonatal care and increased overall survival of preterm neonates, the male sex has been identified as a risk factor for the development of many prematurity-related morbidities. Bronchopulmonary Dysplasia (BPD) is the leading cause of morbidity affecting premature babies, and survivors of BPD have long-standing deficits in lung function and may be at risk for the development of additional lung diseases as adults. The increasing evidence of the role of sex as a biological variable in disease outcome, pathophysiology, and response to therapy has highlighted the gap in neonatal basic, clinical, and translational studies. We were the first lab to highlight the crucial role of sex-specific differences in neonatal hyperoxic lung injury in a murine model and have continued to elucidate molecular mechanisms contributing to sexual dimorphism in the neonatal lung. Fundamental questions remain about the mechanisms by which sex as a biological variable modulates lung injury, repair, and recovery. The scientific premise is based on our recent work that shows that sex chromosomes and not sex hormones mediate the differences in the neonatal lung phenotype following injury. The research proposal addresses these gaps by extending our work in elucidating X-chromosome-mediated epigenetic mechanisms mediating sex-specific differences in neonatal lung injury. This paradigm-shifting work is necessary to identify the sex-biased molecular forces that modify disease in the neonatal period and to explain the resilience and/or susceptibility based on biological sex in human BPD.
A deep reinforcement learning-based system to guide treatment regimens for osteoporosis based on sex and sex hormone dependencies
PI: Xiaowei Liu, PhD
Osteoporosis is a disease characterized by significant reductions in overall bone density and structural integrity, causing skeletal fragility and an increased risk of bone fractures. Current treatments for osteoporosis focus on either inhibiting bone resorption using anti-catabolic agents, such as bisphosphonates, or promoting bone formation using anabolic agents, such as intermittent parathyroid hormone (PTH). However, a therapeutic pause after 3-5 years of bisphosphonate use is recommended. Moreover, there is a limit of 18-24 months on the use of anabolic treatments, and their treatment benefit can be reversed upon discontinuation. Nevertheless, osteoporosis is a life-long chronic condition and there is a pressing need for novel therapeutic regimens to provide continuous osteoporosis management and maintain treatment benefit. Our recent investigation unexpectedly discovered that skeletal responses to the anabolic treatment and discontinuation is sex- and gonadal function-dependent. However, osteoporosis not only affects postmenopausal women, but also aged men. Moreover, though rare, young adults may also suffer from osteoporosis and require treatments. Therefore, inspired by recent successes of machine learning in healthcare, in this pilot grant, we propose to develop a deep reinforcement learning (DRL)-based treatment decision making system to (1) elucidate the influence of sex and gonadal function on skeletal responses to sequential treatment regimens combining anabolic and anti-resorptive agents (2) validate a proof-of-concept framework for personalized treatment regimens to achieve the highest treatment benefit and extend treatment duration by considering subjects’ sex and gonadal functions.
2023 RAISE Pilot Grant Recipients
Changes in contraception and sterilization use patterns among reproductive-age males and females in Pennsylvania following constrained abortion access.
PIs: Paula Chatterjee, MD, MPH; Alice Abernathy, MD, MSHP
Background: Access to effective contraception is essential to sex equity. The US Supreme Court decision Dobbs v. Jackson Women’s Health (Dobbs) reshaped access to abortion and may have produced changes in contraception and sterilization uptake.
Objective: Evaluate changes in contraception use and sterilization procedures for males and females, before and after the Dobbs decision in Pennsylvania, where abortion policy is subject to intense debate, and demographic characteristics permit comparisons of subpopulations of interest.
Hypothesis: Following the Dobbs decision, females shifted contraception use to favor more efficacious methods, and sterilization procedures rose among both males and females, narrowing extant gender gaps in sterilization.
Methods: The exposures include the Dobbs decision 1) leak and 2) final decision. The primary outcomes of interest, contraception use and sterilization, will be identified from claims data from the Pennsylvania Health Care Cost Containment Council. Descriptive statistics will be used to characterize patients seeking contraception and sterilization procedures (age, race, ethnicity, insurance, income, educational attainment, urban vs rural residence, zip code, proximity to abortion clinic). We will plot the unadjusted utilization rates of contraception and sterilization per population per year, before and after the exposures, stratified by sex. We will use an interrupted time series to establish the underlying trend in Pennsylvania which was “interrupted” by Dobbs which will allow us to deduce the impact of Dobbs on contraception use and sterilization procedures among males and females in Pennsylvania.
Brain growth charts for delineating sex and pubertal effects in human neuroanatomy
PIs: Aaron Alexander-Bloch, MD, PhD; Margaret Gardner, PhD; Sheila Shanmugan, MD, PhD;
Russell T. Shinohara, PhD
Sex differences in neuroanatomy must be thoroughly understood if we are to identify and treat the effects of disease or aging in either female or male brains. Yet, sex biases in brain structure remain hotly debated. Previous neuroimaging studies identified widespread sex differences in brain morphology above and beyond sex-differences in total brain size or height, but replicability has been hampered by underpowered samples and lack of rigor in statistical modeling. Sex effects on neuroanatomy are further complicated by puberty, a multiscale developmental process that is strongly correlated with—yet systematically independent from— chronological age. Sex and puberty have interactive, nonlinear, and age-varying effects on brain structure. However, we lack a comprehensive, well-powered quantification of these effects. Here, we will generate sex-informed growth charts of brain development and aging, using a recently validated statistical modeling approach based on consortium-level data comprising over 100,000 MRI scans from 0-100 years (Aim 1). Using validated measures of pubertal stage coupled with over 15,000 MRI scans in participants under age 25, we will then investigate specific contributions of puberty to structural brain development (Aim 2). We propose to demonstrate that accurate, sex-informed brain growth charts improve sensitivity to disease effects in neuropsychiatric disorders, which often have sex differences in symptomatology, prevalence, and age of onset. The results of this project will enable our team to pursue NIH funding for translational studies that deploy sex-specific brain growth charts to analyze clinically-acquired MRIs in a treatment setting and to develop personalized imaging-genetic markers for neuropsychiatric disorders.
Sex Hormones and Inflammatory Biomarkers in Females with Sickle Cell Disease
PIs: Andrea Roe, MD, MPH; Kandace Gollomp, MD
Sickle cell disease (SCD) is characterized by debilitating pain episodes, known as vaso-occlusive crisis (VOC), and there is a significant sex disparity in VOC in SCD: females experience more frequent and more severe VOC than males. Females with SCD also often experience VOC pain, distinct from dysmenorrhea, during the week prior to and during menses. This sex disparity and cyclic pattern raise the possibility of a sex-specific pathophysiology to VOC in SCD. Markers of inflammation are elevated during VOC compared to baseline in SCD, and they also vary across the menstrual cycle in healthy females. We recently analyzed samples from the Penn Medicine BioBank (PMBB) to measure CRP and markers of inflammation and discovered that females with SCD had significantly higher C-reactive protein levels during the follicular phase of the menstrual cycle compared with the luteal phase, which could be linked to the cyclic pattern of VOC. We will use separate funding to recruit 40 patients with SCD during hospitalization for VOC, with repeat assessment after VOC resolution. With the proposed RAISE funding, we seek to characterize classic and novel biomarkers of inflammation, as well as cellular adhesion and clot formation, in what will be the largest cohort of SCD patients assessed at baseline and during VOC. We will stratify this cohort by sex to prospectively validate our preliminary data from the PMBB samples, explore associations with these novel measures, and potentially support our hypothesis that cyclic variation in inflammation across the menstrual cycle predisposes females with SCD to VOC.
What is the difference between sex and gender?
Sex is a multidimensional biological construct based on anatomy, physiology, genetics, and hormones. All animals (including humans) have a sex. As is common across health research communities, NIH usually categorizes sex as male or female, although variations do occur. These variations are called differences in sex development (DSD) or intersex conditions1.
Gender is relevant only for research with humans (not other animals). Gender can be broadly defined as a multidimensional construct that encompasses gender identity and expression, as well as social and cultural expectations about status, characteristics, and behavior as they are associated with certain sex traits1.
Figure. Dimensions of Sex (Biological Variable) & Gender (Social and Cultural Variable)
What is the sex and gender data gap?
The medical sex and gender data gap is well-established2. Despite this fact, and efforts by the NIH including the Sex as a Biological Variable (SABV) policy, the assertion that sex and gender do not matter or are too complex to incorporate, perpetuates the male default bias at every stage of research, from preclinical mice models to clinical trial recruitment 3-5. The lack of sex and gender-disaggregated data has led to an intrinsically biased medical system that is guided by a spurious understanding of disease processes as they present in women. Sex and gender-disaggregated data is also critical to achieving gender equity in academic medicine6.
“What clinicians know about the diagnosis, treatment, and prevention of disease originates from studies mostly done on male cells, male mice, and men”
Figure. Inter-relation between sex and gender in health, diseases, and medicine
References
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National Institutes of Health. Office of Research on Women's Health. What are Sex and Gender? https://orwh.od.nih.gov/sex-gender
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Caroline Criado Perez, Criado Perez. Invisible Women: Data Bias in a World Designed for Men. New York: Abrams Press, 2019.
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National Institutes of Health. Consideration of Sex as a Biological Variable in NIH-funded Research <https://orwh.od.nih.gov/sites/orwh/files/docs/NOT-OD-15-102%20Guidance.pdf>. 2016.
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Zucker I, Beery AK. Males still dominate animal studies. Nature (London). 2010; 465:690.
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Marts SA, Keitt S. Foreword: a historical overview of advocacy for research in sex-based biology. In: Advances in Molecular and Cell Biology. Elsevier B.V, 2004:v-xiii.
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Raj A, Kumra T, Darmstadt G, Freund K. Achieving gender and social equality: More than gender parity is needed. Academic medicine. 2019; 94:1658-1664.
