• Stanford CAM Center for Chronic Back Pain
  3P01AT006651-03S1
  Principal Investigator: Sean C. Mackey, M.D., Ph.D.
  Institution: Stanford University School of Medicine
  This project uses real-time functional magnetic resonance imaging (fMRI) neurofeedback techniques to ascertain the relationship between learned control of specific neural processes and chronic pain reduction. The supplement will stratify, based on opioid use and gender, differences in brain morphology determined by fMRI.

• University of Hawaii Cancer Center Support Grant
  3P30CA071789-14S3
  Principal Investigator: Michele Carbone, M.D., Ph.D.
  Institution: University of Hawaii at Manoa
  This grant supports the University of Hawaii Cancer Center, which aims to reduce cancer burden through research, education, and service; its location in Hawaii offers access to a distinct environment in terms of ethnic diversity and health disparities. The supplement will examine disparities among women related to screening for tobacco use and nicotine dependence.
• City of Hope Comprehensive Cancer Center
  3P30CA033572-30S4
  Principal Investigator: Michael A. Friedman, M.D.
  Institution: City of Hope Beckman Research Institute
  This project is part of a larger NCI-funded Cancer Center Support Grant. The supplement will evaluate outcome differences between men and women with advanced bladder cancer who are treated with a promising new agent, the tubulin inhibitor eribulin. Bladder cancer is more common in men, but bladder-cancer mortality has been reported to be higher in women, and few prospective evaluations have studied this sex-based survival disparity.
• Molecular Biomarkers of Airway and Lung Linking COPD and Lung Cancer
  3R01CA164783-03S1
  Principal Investigator: Marc E. Lenburg, Ph.D.
  Institution: Boston University Medical Center
  This project is developing distinct airway biomarkers of chronic obstructive pulmonary disease (COPD), lung cancer, and both diseases, toward development of more effective tools for lung cancer diagnosis, screening, and targeted chemoprevention. The supplement will analyze additional samples from original cohorts to expand descriptions of sex-specific alterations of gene expression that affect disease in lung tissue and the bronchial airway epithelium.

Novel Mechanism of Action as Therapeutic Strategy for Optic Neuritis
3R01EY022774-02S1
Principal Investigator: Peter Koulin, Ph.D.
Institution: University of Missouri, Kansas City
This project is investigating a novel combination pharmacological intervention strategy to control structural and functional degeneration in autoimmune optic neuritis, a leading cause of blindness in the United States and worldwide. The supplement will add a second group of animals of the opposite sex (female) to those in the original study for comparative analyses of gender-mediated effects and treatment outcomes.

Anticipating Personalized Genomic Medicine: Impact and Implications
3R01HG005277-10S1
Principal Investigator: Eric T. Jeungst, Ph.D.
Institution: University of North Carolina, Chapel Hill
This project is studying the extent to which people who promote, implement, provide, and use "personalized genomic medicine" understand its promises and potential pitfalls. The supplement, focused on interviews with couples considering Fragile X testing, aims to identify sex/gender differences in personal health risks and reproductive genetic risks.

• Arrhythmogenic Remodeling in Human Heart Failure
  3R01HL114395-02S1
  Principal Investigator: Igor R. Efimov, Ph.D.
  Institution: Washington University in St. Louis
  This project aims to bridge the gap between fundamental discoveries in animal models of human heart failure with validation in clinical trials, using explanted hearts of transplantation patients and rejected donor hearts. The supplement will investigate three important areas of sex/gender differences in heart remodeling: activation, repolarization, and calcium handling.
• Sleep Duration Required to Restore Performance During Chronic Sleep Restriction
  3R01HL114088-02S1
  Principal Investigator: Elizabeth B. Klerman, M.D., Ph.D.
  Institution: Brigham and Women's Hospital
  This project is studying short- and long-term consequences of sleep deficiency, which can predispose an individual to attentional lapses, errors, and accidents, especially during the biological (circadian) night — an issue of concern for the 15 percent of Americans who are involved in shift work. The supplement aims to investigate and quantify sex differences in sleep-wake transitions using a large, existing sleep dataset in which sleep was recorded following varying durations of wakefulness.
• New Approaches for Empowering Studies of Asthma in Populations of African Descent
  3R01HL104608-03S1
  Principal Investigator: Kathleen C. Barnes, Ph.D.
  Institution: Johns Hopkins University School of Medicine
  Using discoveries resulting from the 1,000 Genomes Project and select genetic variants that best represent the genome of individuals of African descent, this project is developing a custom DNA-variation chip (the African Power Chip) to complement current, commercially available DNA-sequence chips to study asthma risk in 12,000 individuals. The supplement will identify and replicate genetic variants with sex-specific effects on asthma in 450 African American individuals included in the Consortium on Asthma among African-ancestry Populations in the Americas.

• Johns Hopkins Alzheimer's Disease Research Center
  3P50AG005146-30S1
  Principal Investigator: Marilyn S. Albert, Ph.D.
  Institution: Johns Hopkins University School of Medicine
  The Johns Hopkins Alzheimer's Disease Research Center is conducting dementia research, with a particular focus on the understanding the earliest phases of Alzheimer's disease (AD). Employing a female AD transgenic-mouse model, the supplement will test the hypothesis that cognitive function is more sensitive to the toxic effects of amyloid-beta protein in females than in males.
• Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA-3CT)
  3R01AG037120-03S1
  Principal Investigator: Michael L. Terrin, M.D.
  Institution: University of Maryland, Baltimore
  The N-TA-3CT study is a Phase IIb, randomized clinical trial investigating the effect of doxycycline compared to placebo on the growth of the diameter of abdominal aortic aneurysms. The supplement will enable the investigators to increase the number of women from 50 to 70 in the parent trial, to increase the statistical power to detect gender differences in clinical study outcomes and disease mechanisms.

• Integrative Neuroscience Initiative on Alcoholism: Stress and Ethanol Self-Administration in Monkeys
  3U01AA013510-13S1
  Principal Investigator: Kathleen A. Grant, Ph.D.
  Institution: Oregon Health and Science University
  This research in rhesus monkeys (nonhuman primates that are the most valid model of human alcoholics) studies the role of stress in prompting some individuals to drink alcohol excessively, toward understanding alcohol dependency and its interventions in humans. The supplement will measure biological parameters such as changes in hormones and immune-related proteins (from blood samples already collected in the parent study) that indicate the severity of damage due to heavy alcohol consumption.
• Sex Disparities in Overall Response to ART Among HIV-Infected Individuals
  3U24AA020794-02S2
  Principal Investigator: Amy C. Justice, M.D., Ph.D.
  Institution: Yale University School of Medicine
  The Veterans Aging Cohort Study (VACS) is the largest clinical cohort of HIV-infected individuals in North America and includes in-depth, longitudinal data on alcohol, multi-substance use, and outcomes. This project aims to transform VACS into a new collaboration of research experts, clinicians, patients, and policy makers: the Consortium to improve OutcoMes in HIV/AIDS (COMpAAAS). The supplement will expand investigation (beyond the VA Healthcare system cohort) of the observed sex disparities in treatment response among HIV-infected individuals that appear to be unrelated to socio-demographic characteristics, health behaviors, and access to care.

• Tissue-Specific BorreliaGene Expression
  5R37AI049200-13
  Principal Investigator: Erol Fikrig, M.D.
  Institution: Yale University School of Medicine
  This project focuses on the pathogenesis of, and immunity against, Lyme disease. Because basic immune responses between men and women are known to differ, and because women have a higher prevalence of autoimmune disorders, this supplement will compare immune responses to infection with the Lyme-inducing Borrelia burgdoferi bacterium in male and female mice.
• Estrogen Receptor a Regulation of Lupus Development and Pathogenesis
  5R01AI075167-04
  Principal Investigator: Karen A. Gould, Ph.D.
  Institution: University of Nebraska Medical Center
  This research employs mouse models to determine the mechanisms through which estrogens promote lupus, a prevalent and life-threatening autoimmune disease that affects women predominantly. The supplement aims to define cellular and molecular pathways through which estrogens enhance lupus susceptibility in women.
• Influenza A Virus Infection of Human Nasal Epithelial Cells
  5R01AI097417-02
  Principal Investigator: Andrew S. Pekosz, Ph.D.
  Institution: Johns Hopkins University School of Medicine
  This project is investigating how influenza virus and influenza vaccine strains differ in their ability to replicate in human nasal epithelial cells: In particular, there is growing evidence that females of reproductive age (18-49) are at higher risk for severe disease after influenza infection. The supplement will enable the investigators to acquire additional tissues from male and female donors to identify sex-based differences in viral replication and innate immune response.
• Tuning Fc-Effector Functions of HIV-specific antibodies
  5R01AI102660-02
  Principal Investigator: Galit Alter, Ph.D.
  Institution: Massachusetts General Hospital
  This project will define the mechanism of antibody glycosylation in immune (B) cells, toward the design of improved vaccines. Changes in antibody glycosylation can have systemic inflammatory effects, especially in women. The supplement will explore sex differences in this process, including epigenetic changes, in health and during HIV infection.

MCRC for Rheumatic Diseases in African Americans
3P60AR062755-02S1
Principal Investigator: Gary Gilkeson, M.D.
Institution: Medical University of South Carolina
Research conducted by this Center grant aims to facilitate research translation, in particular supporting genetic and environmental research studies on scleroderma and lupus, both of which disproportionately affect women and African Americans. The supplement will test the hypothesis that female sex hormones increase gut permeability, raise levels of microbial translocation and bacterial ligands, and increase monocyte activation — leading to higher susceptibility to autoimmune diseases in females compared to males.

• Patient Motion Detection and Compensation in SPECT
  3R01EB001457-09S1
  Principal Investigator: Michael A. King, Ph.D.
  Institution: University of Massachusetts Medical School, Worcester
  This project is testing a motion-correction technique to enhance the reliability and utility of single-photon emission-computed tomography (SPECT) imaging used for coronary artery disease risk assessment and stratification. The supplement will determine the clinical value of an additional respiratory-motion correction applied to data from women to increase imaging accuracy.
• Ultrasound-Induced Tissue Damage Assessment
  3R37EB002641-16S1
  Principal Investigator: William D. O'Brien, Ph.D.
  Institution: University of Illinois, Urbana-Champaign
  This project is a basic-science investigation of a potentially significant ultrasound-induced biological effect: Does the use of ultrasound contrast agents cause tissue damage in blood vessels? The supplement will conduct experiments in animals to identify possible sex-based differences, and possible sex-based risks, in the response to a new ultrasound cardiac pacing therapy.

• Integrating Contextual, Proximal, and Individual Risks for Child Conduct Problems
  3R01HD066040-04S1
  Principal Investigator: Alexandra S. Burt, Ph.D.
  Institution: Michigan State University
  Many factors influence development of conduct problems in children, and this project is investigating how neighborhood contextual risk moderates genetic risk — toward development of individually-tailored interventions. The supplement will study 2,000 twin children (aged 6-10, half girls, half boys) and their parents to examine sex differences in gene-environment interactions underlying child conduct problems.
• Host Epigenetic and Mitochondrial Function in HIV-Infected Children
  3R01HD073952-02S1
  Principal Investigator: Louise Kuhn, Ph.D.
  Institution: Columbia University Health Sciences
  This prospective study of 500 treated HIV-infected and 250 uninfected children in South Africa is investigating biological pathways for metabolic complications of HIV infection. The supplement aims to increase enrollment in a nested laboratory sub-study to evaluate sex differences in the pathobiology of these pathways that include mitochondrial dysfunction, chronic inflammation, and HIV-related immune senescence.
• Understanding the Impact of Antipsychotic Drugs on Recovery after Traumatic Brain Injury
  3R01HD069620-02S1
  Principal Investigator: Anthony E. Kline, Ph.D.
  Institution: University of Pittsburgh
  Antipsychotic drugs are commonly used to manage agitation and aggression that often follows traumatic brain injury; however, a paucity of research is available on the effect of these medications on subsequent recovery. This project compares three antipsychotic drugs to assess effects on motor and cognitive recovery after traumatic brain injury. The supplement adds a study of female animals to compare to preliminary results obtained with a male-only sample.

Vestibular Thresholds, Including Psychophysical Response Dynamics
3R01DC004158-12S1
Principal Investigator: Daniel M. Merfeld, Ph.D.
Institution: Massachusetts Eye and Ear Infirmary
The vestibular system of the inner ear detects head/body motion and tilting relative to gravity. This project measures human vestibular perceptual thresholds for tilt, linear, and rotational motion using four new precise and efficient quantitative tests. The supplement adds threshold testing for 50 male and 50 female age-matched normal subjects, paired to determine whether there is a statistically significant sex/gender difference in vestibular perception thresholds over a wide age range.

Cortico-Striatal Plasticity in the Transition to Chronic Pain
3R01DE022746-02S1
Principal Investigator: Apkar V. Apkarian, Ph.D.
Institution: Northwestern University
This project, which combines brain imaging with cellular, molecular, and electrophysiological assays in mice and rats and then in humans with back pain, is based on the idea that brain emotional and motivational learning circuitry is an integral part of the transition from acute to chronic pain. The supplement increases statistical power to test for gender dependence of both analgesic efficacy and transition from acute to chronic low back pain.

• Lactation and Incidence of Diabetes Mellitus in CARDIA Women
  3R01DK090047-03S1
  Principal Investigator: Erica P. Gunderson, Ph.D.
  Institution: Kaiser Foundation Hospitals
  As part of the larger Coronary Artery Risk Development in Young Adults Study (CARDIA) population-based study, this project investigates effects of breastfeeding on prevention of type 2 diabetes. The supplement enables contrast of biological and lifestyle effects to determine sex differences in cardiometabolic risk, in men and women, by assessing the impact of childbearing (as a "lifestyle" effect) on both sexes.
• Localization of Saturated Diacylglycerol and Insulin Sensitivity in Humans
  3R01DK089170-04S1
  Principal Investigator: Bryan C. Bergman, Ph.D.
  Institution: University of Colorado, Denver
  This project is investigating fundamental mechanisms that underlie insulin resistance, which is often less prevalent in women than men of the same age, body mass index (BMI), and ethnicity. The supplement will expand on preliminary observations showing that women have a lower saturated to unsaturated fatty acid ratio in skeletal muscle, by increasing the number of obese subjects to permit a statistically relevant gender-specific data analysis.
• Discovery and Fine Mapping of Susceptibility Loci for IgA Nephropathy
  3R01DK095510-02S1
  Principal Investigator: Ali G. Gharavi, M.D.
  Institution: Yale University School of Medicine
  This project is conducting genetic studies related to immunoglobulin A nephropathy, an understudied disease that is a major cause of kidney failure in the United States and worldwide. The supplement will analyze genome-wide association data stratified by gender to look for clues to help explain the striking gender disparity in this condition.

• Mechanisms of Nicotine Reinforcement
  3R01DA020686-07S1
  Principal Investigator: Paul J. Kenny, Ph.D.
  Institution: The Scripps Research Institute, Florida
  This project first identified nicotinic acetylcholine receptor subtypes in the midbrain and thalamus that limit nicotine consumption, and its ongoing studies are looking for other therapeutic targets for smoking cessation. The supplement will expand studies investigating sex-specific differences in nicotine consumption using transgenic rats, including follow-up analyses of a genetic variant associated with schizophrenia and results suggesting a correlation between nicotine response and sexual behavior.
• Assess the Effects of Environmental Tobacco Smoke on Neurodevelopment
  3R01DA027100-04S1
  Principal Investigator: Virginia A. Rauh, Sc.D.
  Institution: Columbia University Health Sciences
  This project is assessing the effects of environmental tobacco smoke exposure on brain development and neurobehavioral functioning in inner-city children. Toward identifying biological and behavioral trajectories associated with environmental tobacco smoke exposure, the supplement will combine male and female subjects from two ongoing prospective studies to obtain adequate statistical power for sex-specific analyses of preexisting data.
• Drug Abuse Vulnerability: Mechanisms and Manifestations
  3P50DA005605-22S1
  Principal Investigator: Duncan B. Clark, MD., Ph.D.
  Institution: Western Psychiatric Institute and Clinic, University of Pittsburgh
  This grant funds the Center for Education and Drug Abuse Research, which was established in 1989 as part of a larger research effort to understand the etiology of substance use disorder, toward development of methods and instruments to identify at-risk youth. The supplement will derive and validate six age-specific versions of a transmissible liability index for girls and young women, akin to a similar transmissible liability index developed for boys and young men.
• Neuronal Substrates of Cocaine Reward
  3R01DA004398-26S2
  Principal Investigator: George F. Koob, Ph.D.
  Institution: The Scripps Research Institute, La Jolla
  This project is studying the role of stress in the compulsivity that is associated with cocaine dependence, vulnerability, and potential treatments. Both clinical human and pre-clinical animal studies indicate that compared to males, females exhibit enhanced cocaine-seeking within all stages of addiction. The supplement will expand a male-only study by adding female rats to investigate sex differences in stress-system neuroadaptations underlying addiction.
• Development of the Basal Telencephalic Limbic System 
  3R01DA020140-09S2 
  Principal Investigator: Joshua G. Corbin, Ph.D.
  Institution: Children's National Medical Center
  This project is investigating the genetic and cellular basis of development of the amygdala, a brain region that coordinates appropriate behavioral responses to stimuli with emotional and motivational salience. The supplement will assess sex-based differences in functional and molecular properties of subsets of amygdala neurons using developmentally regulated genetic tools.
• Human Methamphetamine Vaccine: Translational Avante Garde Award
  3DP1DA033502-03S1
  Principal Investigator: Thomas R. Kosten, M.D.
  Institution: Baylor College of Medicine
  This research is a collaborative project between American and Chinese investigators and manufacturers to develop a first-, and potentially a second-, generation human methamphetamine vaccine to enter quickly into clinical development in the United States and Asia. The supplement will incorporate sex-differences analyses into efficacy tests in rats, based on known differences between men and women in immunological vaccine responses.

Mechanisms of Asthma-Dietary Interventions against Environmental Triggers
3P01ES018176-05S1
Principal Investigator: Shyam Biswal, Ph.D.
Institution: Johns Hopkins University School of Medicine
Using well-controlled mouse-model studies, this research aims to better understand the relationship between dietary intake and asthma. The supplement will allow sex differences to be examined for all parameters of the project's population-based study and will compare the effects of air pollution and diet on asthma in female and male mice.

• Receptor Selective Spinal Analgesia
  3R37GM048085-21S1
  Principal Investigator: James Eisenach, M.D.
  Institution: Wake Forest University Health Sciences
  This project explores the clinical observation that trauma during childbirth very rarely causes chronic pain, in an effort to understand this protective effect and apply it to other settings. The supplement will investigate sex differences in spinal astrocyte activation after injury, and it will assess the relevance of sex differences on spinal astrocyte activation to hypersensitivity.
• An Intercross Between the Circadian and NFkB Pathways
  3R01GM095874-03S1
  Principal Investigator: Marina Antoch, Ph.D.
  Institution: Roswell Park Cancer Institute
  This research explores how biological clocks and the immune system interact at the molecular level. The supplement will look for sex-specific differences in an organismal response (male or female mice) to acute stressors using a key immune regulatory system, the NF-?B signaling pathway.

• HIV Prevention Intervention for Young Transgender Women
  3R01MH094323-03S1
  Principal Investigator: Matthew J. Mimiaga, Sc.D.
  Institution: Ann & Robert H. Lurie Children's Hospital of Chicago
  This project tests the efficacy of a uniquely targeted HIV risk-reduction intervention for young transgender women (16-24) who are at risk for HIV acquisition or transmission. The supplement will compare sexual risk behaviors and psychosocial risk and resilience factors between transgender women and transgender men who have sex with men. This approach enables separation of sex (biological) and gender (behavioral/cultural) factors.
• Characterization of Leptins' Antidepressant Activity
  3R01MH076929-06A1S1
  Principal Investigator: Xin-Yun Lu, M.D., Ph.D.
  Institution: University of Texas Health Science Center, San Antonio
  This project aims to understand the causes and disease progression of depression-related behaviors and to explore the role of the adipocyte hormone leptin in mood regulation. Since the parent grant only employed male subjects, the supplement will add sufficient numbers of females to investigate sex differences in mood and difficulty experiencing pleasure.
• In Utero Programming of the Dopamine System: Behavior, Neuroanatomy, and Epigenetics
  3R01MH087978-04S1
  Principal Investigator: Teresa M. Reyes, Ph.D.
  Institution: University of Pennsylvania School of Medicine
  Intrauterine growth retardation can lead to neurobehavioral disabilities, including an increased risk for attention deficit hyperactivity disorder (ADHD). This project employs an animal model to explore potential causes and interventions. The supplement may shed light on gender differences in ADHD by examining the effect of restricted maternal dietary intake on behavior in male and female offspring, as well as on patterns of DNA methylation and gene expression in male and female offspring.

• Retrospective Cohort Study of Racial Disparities in HIV Survival, Florida
  3R01MD004002-05S1
  Principal Investigator: Mary Jo Trepka, M.D.
  Institution: Florida International University
  This study examines the role of various factors such as socioeconomic status, segregation, and rural residence in causing a survival disadvantage for HIV-infected African Americans, and it includes a focus on sex/gender differences in HIV morbidity and mortality. The supplement expands this focus to include transgender individuals with HIV. This approach enables a unique examination of sex (biological) and gender (behavioral/cultural) influences, providing an opportunity to disentangle biological and non-biological factors related to HIV/AIDS.
• Addressing Disparities in Chronic Disease with a Teen and Young Adult Focus
  3P60MD006902-02S1
  Principal Investigator: Kirsten Bibbins-Domingo, M.D., Ph.D.
  Institution: University of California, San Francisco
  This project funds the center for health and risk in minority youth and adults (CHARM), which is dedicated to chronic disease prevention in racial/ethnic minority communities in the San Francisco Bay Area, focusing in particular on youth and young adults. The supplement will extend a current study of childhood asthma and obesity in Latino Americans to identify sex-specific differences in the obese asthma phenotype and to uncover the contributions of genetics, socio-demographics, and early-life events in the development of these conditions in Latino and African American girls and boys.

• Estrogen-Induced Hippocampal Seizure Susceptibility
  3R01NS037324-15S1
  Principal Investigator: Catherine S. Woolley, Ph.D.
  Institution: Northwestern University
  This research is defining novel mechanisms by which estrogen affects levels of neurotransmitters and neuropeptides in the hippocampus, a key brain region involved in epilepsy. The supplement will look for sex-based effects of brain-synthesized estrogens on limbic seizures, and it will also test for sex differences in estrogen function in the hippocampus.
• MECP2 Modulation of BDNF Signaling Shared Mechanism of Rett and Autism
  3R01NS065027-04S1
  Principal Investigator: Lucas D. Pozzo-Miller, Ph.D.
  Institution: University of Alabama at Birmingham
  This project studies Rett syndrome, an X-linked neurodevelopmental disorder associated with autism and mental retardation and which is more common in girls and that is known to be caused by a genetic mutation that affects production of a neuronal growth factor. The supplement will extend the project's reach by including an analysis of hippocampal function in female transgenic mice; the original project included only male animals.
• Failure of Metabolite Clearance in a Model of Multi-Lacunar Infarcts
  3R01NS078167-02S1
  Principal Investigator: Maiken Nedergaard, M.D., Ph.D.
  Institution: University of Rochester
  This research tests the hypothesis that accumulation of metabolic waste products contributes to impairment of cognitive functions in a mouse model of multi-infarct dementia. The supplement will evaluate the effect of age and tissue injury on the clearance of waste fluid in the brains of male and female mice.
• Inflammasome Activation in Complex Regional Pain Syndrome
  3R01NS072143-02S1
  Principal Investigator: David J. Clark, M.D., Ph.D.
  Institution: Veterans Administration Palo Alto Health Care System
  This project investigates Complex Regional Pain Syndrome (CRPS), a common neurological condition causing chronic pain and disability that has been recently linked to innate-immunity triggered inflammation. Women are affected by CRPS four times more frequently than are men and may respond differently to treatment, but experiments to date have been conducted exclusively on male animals. The supplement adds a study of female animals, to ascertain the sex-dependence of CRPS severity and duration using multidimensional experimental outcomes mirroring those experienced by humans.

The Influence of Gender on Symptom Characteristics During Acute Coronary Syndrome
3R01NR012012-05S1
Principal Investigator: Holli A. Devon
Institution: University of California, Davis
This project explores gender differences in the symptoms of acute coronary syndrome. The supplement adds a sample of Mexican-American women and men to the parent study. This addition will permit subgroup analyses by gender and also includes an ethnic minority underrepresented in acute coronary syndrome research.