The Specialized Centers of Research Excellence (SCORE) on Sex Differences program is one of two signature, multi-component programs of the Office of Research on Women’s Health.

Each SCORE program serves as a national resource for translational research, at multiple levels of analysis, to identify the role of biological sex differences on the health of women. Centers of Excellence are vital hubs for research on sex and gender that also provide pilot funding, training, and education. SCORE investigators provide leadership in the development and promotion of standards and policies for the consideration of sex as a biological variable (SABV) and sex differences in biomedical research. Identifying the contributions of biological sex can assist in understanding the diversity of health outcomes, and how this knowledge can be applied to the development of the next generation of interventions and medical treatments leading to improvements in women's health. 

The current SCORE U54 program leverages over 15 years of our prior investment to create a disease-agnostic, research program focused on sex differences and major medical conditions affecting women in the US. With support from our NIH IC partners, the P50 Centers program funded established scientists at centers across the country integrating basic, clinical, and behavioral research approaches to incorporate sex differences, leading to seminal contributions to the study of sex differences that affect women’s health. The current ORWH SCORE program remains the only NIH cooperative program supporting disease-agnostic research on sex differences.

ORWH published the Specialized Centers of Research Excellence (SCORE) on Sex Differences (U54 Clinical Trial Optional) RFA in FY 2018, funding 6 new awards. A second RFA, RFA-OD-19-013, was released in November 2018 to support additional programs. Each SCORE program has three highly integrated, synergistic research projects, and an administrative core.  The Career Enhancement Core is a new feature of the program whose goal is to support pilot research and training projects and ensure the next generation of leadership in the development and promotion of standards and policy for the consideration of sex differences in biomedical research.

For more information about the SCORE program please contact SCOREU54@od.nih.gov.

SCORE Directors: Drs. Igho Ofotokun and Lisa B. Haddad 
Grant: U54AG062334
Title: Emory Specialized Center of Research Excellence (SCORE) on Sex Differences

OVERVIEW:
The Emory SCORE is focused on the influence of biological sex on microbial–host–pathogen interactions, using HIV as a model for probing the nature of these interactions. The working hypothesis is that HIV-induced inflammation co-acts with that induced by estrogen insufficiency to heighten the inflammatory state among women living with HIV, thereby worsening age-related comorbidities in this population. The long-term goal of the Emory SCORE is to develop a program to serve as a regional hub for studying the influence of biological sex on the outcomes of infectious diseases and for promoting the normalization of sex as a biological variable (SABV) in research.

RESEARCH PROJECTS: 
Three cross-cutting research projects will explore the synergy between HIV-induced immune activation and chronic inflammation and that induced by estrogen insensitivity observed in women aging with HIV infection.

  • Research Project 1: Neuro  hypothalamic–pituitary–adrenal axis 
    MPIs: Gretchen Neigh, Ph.D., and Vasiliki Michopoulos, Ph.D.

    The goal of the project is to identify factors contributing to HIV-associated chronic inflammation in women. These studies are critical for providing the framework needed to design therapeutic strategies aimed at resolution of the chronic inflammation in women living with HIV.
     
  • Research Project 2: Musculoskeletal 
    MPIs: M. Neale Weitzmann, Ph.D., and Igho Ofotokun, M.D. 

    The project will test the hypothesis that enhanced fracture risk observed in women living with HIV is caused by the collision between HIV/antiretroviral therapy–induced inflammation and that induced by estrogen insufficiency as women living with HIV age.
     
  • Research Project 3: Cardiovascular 
    MPIs: Arshed Quyyumi, M.D., and Leslee J. Shaw, Ph.D.

    The goal of the project is to assess the combined immune effects of HIV and estrogen status described in Project 1 and Project 2 on cardiovascular health as assessed by endogenous reparative/regenerative capacity (circulating progenitor cells) and the development/progression of subclinical coronary (CT angiography) and carotid artery (MRI) atherosclerosis in women living with HIV compared with HIV-negative controls. 
     

CAREER ENHANCEMENT CORE:

Co-Directors: Marcia Holstad, Ph.D., and Kelli Stidham Hall, Ph.D.

The role of the Career Enhancement Core (CEC) is to prepare the next generation of women’s health researchers to capitalize on Emory’s considerable strengths in prevention science, infectious disease research, clinical and translational research, basic immunology, and antiviral drug development within the context of the National Institutes of Health’s (NIH) recently outlined steps to promote sex considerations in the design and conduct of all research, including the basic sciences.
The CEC will accomplish this through three specific aims:

  • Aim 1.  Administer individual-level career enhancement services that: 
    • Fund meritorious pilot projects of new and early established investigators whose careers are focusing on women’s health research and sex/gender science;
    • Provide support services for the development and maintenance of productive mentor/mentee relationships among investigators conducting women’s health research and sex/gender science; and
    • Integrate CEC participants into training and educational activities that are relevant to the SCORE mission and sponsored by the Emory SCORE, SCORE partners, or other Emory-based organizations. 
  • Aim 2.  Develop and lead collective-level career enhancement services that will train, build, and support a community of science for investigators who are focusing on women’s health research or are engaged in studies that are affected by sex/gender science techniques and findings.
  • Aim 3.  Enable global-level career enhancement through the development and deployment of a massive open online course (MOOC) on sex/gender science.

SCORE Director: Dr. Sabra L. Klein 
Grant: U54AG062333
Title: Sex and Age Differences in Immunity to Influenza (SADII)

OVERVIEW:
The Sex and Age Differences in Immunity to Influenza (SADII) SCORE is positioned to transform our understanding of the role of biological sex, gender, and aging on immune responses to influenza vaccination, which has global public health implications, affecting millions of people worldwide. The overarching hypothesis: Female-biased vaccine-induced immunity to influenza viruses is age-dependent and reflects both hormonal and genetic differences between the sexes that impact immune responses (i.e., both effector and memory)  to influenza vaccine antigens. The SADII SCORE brings together investigators focused on 1) seasonal influenza vaccination in an existing age and sex-stratified human population; 2) animal models that can test hypotheses and mechanisms of action that are inferred from studies in human populations; and 3) the contributions of age, frailty, sex, and gender to vaccine outcomes using quantitative and qualitative statistical models.

RESEARCH PROJECTS:

  • Research Project 1: Sex differences in longitudinal humoral immunity against influenza in the frail elderly

    This research project is led by Dr. Sean Leng, in collaboration with the Johns Hopkins University Older Americans Independence Center. The goal of this project is to provide a detailed analysis of sex and gender differences in humoral immunity and adverse reactions to seasonal influenza vaccines in combination with age and frailty in an existing longitudinal cohort of older individuals. 
     
  • Research Project 2: Sex differences in immune responses to vaccine and circulating strains of influenza in health care workers

    This research project is led by Dr. Andrew Pekosz, in collaboration with the Johns Hopkins Center of Excellence in Influenza Research and Surveillance (JH-CEIRS). The study will characterize the number and transcriptional activity of B cells, as well as humoral immune responses and adverse reactions, following receipt of seasonal influenza vaccines. The study will be focused on men and women between the ages of 18 and 45, to provide an age- and sex-stratified cohort to assess sex differences in vaccine responses among adults. 
     
  • Research Project 3: Genetic and hormonal mechanisms of sex differences in immune responses and influenza vaccine efficacy in young and aged mice

    This research project is led by Dr. Sabra Klein. The goal of the project is to uncover the genetic, hormonal, and age-associated changes in B cells that mediate sex and age differences in vaccine-induced immunity to influenza. This will be accomplished by a systematic evaluation of the effects sex hormones and genes encoded by sex chromosomes have on the antibody response to influenza vaccination.
     

CAREER ENHANCEMENT CORE:
CEC Director:
Wendy Bennett, M.D.

The SADII Career Enhancement Core (CEC) is led by Dr. Wendy Bennett, in collaboration with the Johns Hopkins Center for Women’s Health, Sex, and Gender Research. Aims include: 

  • Providing collaboration, networking, dissemination, and mentoring opportunities; 
  • Providing pilot grant funding for early-stage investigators (i.e., investigators at the level of Assistant Professor or below), with emphasis on diversity of candidates, interested in incorporating sex differences into their clinical, translational, or basic science research in the broad area of immunology (e.g., asthma and allergy, autoimmunity, cancer, infectious diseases, inflammation, microbiome, and vaccines); 
  • Integrating educational opportunities focused on teaching skills and methods for incorporating sex as a biological variable and gender considerations when planning, analyzing, and reporting data, as well as research dissemination activities in regard to a broad range of existing training programs (e.g., KL2 and BIRCWH programs); and 
  • Evaluating the effectiveness of the SADII CEC in expanding learning opportunities, dissemination of sex and gender research, mentorship, and funded research. 

SCORE Directors: Michelle M. Mielke, Ph.D., and Virginia M. Miller, Ph.D.
Grant: U54AG044170-06    
Title: Sex-Specific Effects of Endocrine Disruption on Aging and Alzheimer’s Disease 

OVERVIEW:
The Mayo Clinic Specialized Center of Research Excellence (SCORE) on Sex Differences promotes interdisciplinary approaches to advance translational research on sex differences in health and disease. Research bridges results from basic science projects to clinical studies. The goal of the Mayo Clinic SCORE on Sex Differences is to understand how female-specific conditions associated with major hormonal shifts (e.g., menarche, pregnancy, and menopause) affect physical and cognitive decline in women as they age. During the first funding period (2012–2018), the Mayo Clinic SCORE’s research focused on how the sex-specific conditions of hypertensive pregnancy disorders and natural menopause, with and without menopausal hormone therapy, affected the risk of cardiovascular disease and cognitive decline. In this renewal application, the Mayo Clinic SCORE will extend these investigations to an extreme model of endocrine disruption: premenopausal bilateral salpingo-oophorectomy (BSO). About 1 in 8 women in the United States undergo BSO before reaching natural menopause. Although premenopausal BSO confers protection against ovarian cancer, it is associated with increased all-cause mortality, dementia, Alzheimer’s disease (AD) pathology, cardiovascular disease, skin aging, and sexual dysfunction. Given the large number of aging women with a history of premenopausal BSO, there is an urgent need to understand the long-term physical and cognitive outcomes to empower women considering prophylactic BSO to make more informed decisions. The central hypothesis of the Mayo Clinic’s SCORE renewal is that the abrupt endocrine disruption caused by premenopausal BSO will accelerate pathological aging processes that manifest as reductions in physical and cognitive function and in AD. This hypothesis will be tested through three interrelated translational projects, which are supported by three interdependent cores. 
 

RESEARCH PROJECTS: 

  • Research Project 1: Effects of bilateral salpingo-oophorectomy on physical and cognitive aging
    PI: Michelle M. Mielke, Ph.D.
    Co-Investigators: Walter A. Rocca, M.D., Julie A. Fields, Ph.D., and Nathan K. LeBrasseur, Ph.D.

    The primary objective of Project 1 is to determine whether premenopausal bilateral salpingo-oophorectomy (BSO) is associated with accelerated aging as measured by a higher frailty score, a greater decline in physical and cognitive function, and higher plasma levels of senescence-associated secretory phenotype (SASP) proteins compared with referents. The SASP proteins are also used as the primary aging biomarker in Project 3.
     
  • Research Project 2: Effects of bilateral salpingo-oophorectomy on imaging biomarkers of Alzheimer’s disease and cerebrovascular diseases 
    PI: Kejal Kantarci, M.D.
    Co-Investigator: Kent R. Bailey, Ph.D.

    The primary objective of Project 2 is to assess the effects of premenopausal bilateral salpingo-oophorectomy (BSO) on neuroimaging measures of Alzheimer’s disease and cerebrovascular pathology and to determine whether APOE-ε4 modifies these effects. In addition, the relationship between the neuroimaging biomarkers and the cognitive outcomes measured in Project 1 will be determined.
     
  • Research Project 3: Effects of bilateral ovariectomy on the biology of physical and cognitive aging in mice
    PI: Nathan K. LeBrasseur, Ph.D.
    Co-Investigators: Marissa J. Schafer, Ph.D., and Sundeep Khosla, M.D.

    As a mechanistic complement to the human projects, Project 3 will use mice, with the primary objective of determining the effects of ovariectomy (OVX) on cellular senescence, senescence-associated secretory phenotype (SASP), and measures of physical and cognitive function that parallel those in Projects 1 and 2. In addition, the temporal sequence and tissue-specific effects of estrogen replacement therapy on cellular senescence will be determined.
     

CAREER ENHANCEMENT CORE:
CEC Director:
Virginia M. Miller, Ph.D.

The Career Enhancement Core (CEC) will provide career enrichment, leadership training, and funds to support ancillary studies of the main projects to stimulate new interest in sex differences and women’s health. The Mayo Clinic SCORE will serve as a vital hub for education and dissemination of innovative sex-based translational research methods, results, and best practices. The Mayo Clinic SCORE’s integrated approach for research, training, and education is consistent with the goals of the SCORE on Sex Differences program and ensures continuing research in areas of women’s health and sex differences by training the workforce of the future. 
 

RESOURCE SUPPORT CORE – CLINICAL:
Core Director:
Ekta Kapoor, M.B.B.S.

The Resource Support Core – Clinical will provide centralized, coordinated support, management, and oversight for the human studies of the SCORE (Projects 1 and 2). Specific functions include recruiting, screening, consenting, and enrolling study participants; coordinating and completing clinical and neuroimaging visits; and maintaining and managing a shared database.

SCORE Directors:  Drs. Aimee L. McRae-Clark and Kathleen T. Brady
Grant: U54DA016511
Title: MUSC Specialized Center of Research Excellence on Sex Differences

OVERVIEW:
The MUSC SCORE is an interdisciplinary research center focused on how sex and gender influence addiction and stress-related disorders. It serves as a focal point for women’s health research at MUSC and comprises three core research components—a leadership administrative core, a career enhancement core, and a biostatistics support core—and a pilot project program. The MUSC SCORE’s core scientific projects focus on sex and gender differences in the relationship between addiction and stress response using emerging technology in closely aligned clinical and basic science projects. The overarching goals of the center are to support and improve the translational scientific collaborations of the core and pilot research projects, catalyze further growth of interdisciplinary sex- and gender-based research on the MUSC campus, and create strategic partnerships to enhance the translation and dissemination of SCORE findings and other relevant research to improve the health of women and girls.
 

RESEARCH PROJECTS: 
The three well-integrated translational research projects will investigate sex differences in cannabis and opioid use disorders and directly inform addiction treatment development.

  • Research Project 1: Impact of progesterone on stress reactivity and cannabis use
    MPIs: Aimee McRae-Clark, Pharm.D., and Michael Saladin, Ph.D.
    Co-Investigators: Kevin Gray, M.D., Brian Sherman, Ph.D., and Rachel Tomko, Ph.D.

    The goal of Project 1 is to extend previous findings to assess the efficacy of exogenous progesterone administration for reduction in stress cue reactivity among male and female cannabis users.
     
  • Research Project 2: Impact of lofexidine on anxiety, craving, and opioid use in men and women with opioid use disorder

    MPIs: Kathleen Brady, M.D., Ph.D., and Connie Guille, M.D.
    Co-Investigators: Kelly Barth, D.O., and Jenna McCauley, Ph.D.

    Project 2 will explore gender differences in the impact of an alpha-2 adrenergic agonist (lofexidine) on the relationships among stress, craving, and drug use in individuals with opioid use disorders (OUDs).

  • Research Project 3: Sex differences in the impact of conditioned stress on heroin and cannabis use and seeking

    MPIs: Peter Kalivas, Ph.D., and Carmela Reichel, Ph.D.
    Co-Investigator: Constanza Keller, Ph.D.

    The goal of Project 3 is to test the hypothesis that sex differences in the effects of stress on heroin and cannabis use are related to differences of synaptic plasticity and that pharmacological interventions targeting this plasticity will effectively diminish heroin and cannabis self-administration. 
     

CAREER ENHANCEMENT CORE:
CEC Director:
Virginia M. Miller, Ph.D.

The Career Enhancement Core (CEC) will provide career enrichment, leadership training, and funds to support ancillary studies of the main projects to stimulate new interest in sex differences and women’s health. The Mayo Clinic SCORE will serve as a vital hub for education and dissemination of innovative sex-based translational research methods, results, and best practices. The Mayo Clinic SCORE’s integrated approach for research, training, and education is consistent with the goals of the SCORE on Sex Differences program and ensures continuing research in areas of women’s health and sex differences by training the workforce of the future. 
 

BIOSTATISTICAL RESOURCE CORE:
MPIs:
Viswanathan Ramakrishnan, Ph.D., and Nathaniel Baker, M.S.

The Biostatistical Resource Core provides centralized support to the entire MUSC SCORE team of investigators and strives to promote synergy in terms of study design and analyses across projects and other shared resources. It also contributes to the career enhancement mission of the MUSC SCORE.

SCORE Director: Dr. Karen Reue 
Grant: U54DK120342-01
Title: Sex Differences in the Metabolic Syndrome     

OVERVIEW:
The objective of the UCLA SCORE is to elucidate sex differences in risk factors and treatments for metabolic syndrome (MetSyn) components, such as obesity, insulin resistance/diabetes, dyslipidemia, and fatty liver. Differences between men and women in susceptibility to cardiometabolic disease are well known, but the underlying genetic and physiological mechanisms remain poorly defined. Our goal is to identify factors that determine sex-specific MetSyn risk, which may lead to better diagnosis and treatment for both sexes. A unique feature of the UCLA SCORE is the investigation of sex differences in MetSyn from multiple perspectives, including the impact of having an XX versus an XY sex chromosome complement, interactions between sex and genetic variation, and estrogen effects. This triad converges in the study of how each of these components influences metabolism at the genetic and epigenetic levels. 


RESEARCH PROJECTS: 
The UCLA SCORE consists of three cross-cutting research projects and three cores and will use preclinical models and human tissue samples. 

  • Research Project 1: Sex chromosome effects on metabolic syndrome risk and treatment
    Lead: Karen Reue, Ph.D.

    This project will build on the finding that the presence of XX compared with XY chromosomes increases susceptibility to obesity and related traits. Much of the XX effect is attributable to a specific X chromosome gene that escapes X chromosome inactivation and acts at higher levels in female (XX) compared with male (XY) cells. The effects of this gene dosage on the epigenetic regulation of gene expression, energy balance, and adipose tissue remodeling during obesity will be defined. Also, the XX chromosome effect on increased female risk for diabetes secondary to statin drug therapy will be elucidated, and a dietary co-therapy that may alleviate this sex-biased adverse drug response will be tested. 
     
  • Research Project 2: Gene-by-sex interactions in mitochondrial functions and metabolic syndrome traits
    Lead: Jake Lusis, Ph.D.

    This project seeks to understand the roles of both genetics and sex in metabolic syndrome (MetSyn) traits. Results of a systems genetics approach have implicated sex- and tissue-specific action of specific genes on MetSyn traits. The project will elucidate sex effects on mitochondrial functions in insulin resistance, as well as sex-specific effects of genes that have been implicated in insulin resistance and hepatic steatosis. The gene-by-sex interactions discovered in mice will be tested in tissues from human cohorts. 
     
  • Research Project 3: The impact of estrogen receptor (ER) in metabolic health
    Lead: Andrea Hevener, Ph.D.

    This project will test the hypothesis that muscle estrogen receptor (ER) protects against metabolic dysfunction in mice and women, identify ER regulatory sites across the genome in females and males, and elucidate the effect of ER on the regulation of mitochondrial function. Results may provide proof-of-concept evidence that skeletal muscle ER is an effective therapeutic target to combat metabolic dysfunction and type 2 diabetes. 
     

CAREER ENHANCEMENT CORE:

Lead: Arthur P. Arnold, Ph.D.

The Career Enhancement Core (CEC) proposes an integrated set of educational and research support activities to foster development of research at UCLA in women’s health and sex as a biological variable (SABV) in disease, especially related to sex differences in metabolic syndrome. The aim is to spread the word about when and how sex has an important effect on physiology and disease and to teach best practices for investigating sex-biasing factors (e.g., gonadal hormones and sex chromosomes) that affect disease. The CEC intends to seed and incubate fledgling research projects and build an interactive community of investigators at UCLA and nationally that consider women’s health and sex differences in their research. Key activities include workshops on clinical and experimental approaches to study SABV, a Pilot and Feasibility grant program to enhance the ability of investigators to perform SABV-relevant research, and lectures by invited speakers who study women’s health and SABV, in coordination with UCLA undergraduate programs and courses. Involvement of underrepresented minority students in exciting research on women’s health and SABV will be emphasized.
 

GENOMIC TECHNOLOGIES CORE:

Lead: Matteo Pellegrini, Ph.D.

The Genomic Technologies Core provides next-generation sequencing and bioinformatic analysis of transcriptomic RNA sequencing, ATAC-seq, and ChIP-seq data to enhance understanding of molecular mechanisms underlying sex differences in metabolic syndrome. 

Additional information is available at https://sexdifferencesinmetabolism.ucla.edu.

SCORE Director: Dr. Wendy M. Kohrt 
Grant: U54AG062319
Title: Bioenergetic and Metabolic Consequences of the Loss of Gonadal Function

OVERVIEW: The University of Colorado Specialized Center of Research Excellence on Sex Differences (CO-SCORE) is thematically focused on bioenergetic and metabolic consequences of the loss of gonadal function. The overarching scientific objective of the CO-SCORE is to advance knowledge of the impact of gonadal aging on the regulation of bioenergetics, abdominal adiposity, and metabolism by conducting mechanistically driven research across the basic-to-clinical translational spectrum. The scientific premise is that gonadal failure mediates biological changes that increase risk for chronic disease. The most well-studied example of this is the accelerated decline in bone mineral density at menopause and the associated osteoporosis risk. However, the extent to which gonadal failure increases risk for chronic diseases other than osteoporosis is poorly understood. The three research projects (basic, preclinical, and clinical) will advance cutting-edge, paradigm-challenging translational research on novel mechanisms postulated to contribute to the increased abdominal adiposity and associated metabolic dysfunction that occur in the estrogen-deficient state. 
 

RESEARCH PROJECTS:

  • Research Project 1: Bioenergetic and metabolic consequences of the loss of gonadal function in women
    PI: Wendy M. Kohrt, Ph.D.
    Co-Investigators: Daniel H. Bessesen, M.D., Edward L. Melanson, Ph.D., Kerrie L. Moreau, Ph.D., and Margaret E. Wierman, M.D.

    Project 1 is based on the overarching hypothesis that the loss of gonadal function increases risk for chronic disease. This is particularly relevant to women’s health because gonadal failure is inevitable in women in midlife but rare in men until much later in life. Aim 1 in the current award period is to determine whether adipose tissue and systemic glucocorticoid metabolism are regulated by E2 in women. Because a goal of the CO-SCORE is to advance paradigm-challenging research on sex differences, Aim 2 will investigate follicle-stimulating hormone (FSH) as a mediator of energy homeostasis and cardiometabolic function. Projects 1, 2 (preclinical), and 3 (basic) will all address gaps in knowledge on whether the effects of estradiol (E2) deficiency to increase abdominal adiposity are  mediated by altered glucocorticoid metabolism and/or increased FSH. Adipose tissue samples from women in Project 1 and from animals in Projects 2 and 3 will be interrogated using similar approaches to accelerate the translational relevance of these areas of research. Finally, because blood and tissue samples from experiments in which we control E2 status are of great value across many disciplines, we will bank specimens from women in Project 1 so they can be used to support external collaborations with SCORE (and other) investigators across the country.
     
  • Research Project 2: Mediators of metabolic decline with the loss of gonadal function
    PI: Paul S. MacLean, Ph.D.
    Co-Investigators: Matthew R. Jackman, Ph.D., Michael C. Rudolph, Ph.D., and Elizabeth A. Wellberg, Ph.D.

    The overarching scientific objective of the CO-SCORE is to advance our understanding of how gonadal aging affects bioenergetics, abdominal adiposity, metabolism, and disease risk by conducting mechanistically driven research across the basic-to-clinical translational spectrum. CO-SCORE Project 2 will leverage preclinical models and interventions to provide a bidirectional, basic-to-clinical translational bridge between the clinically relevant studies of Project 1 and the basic discovery studies in Project 3. The long-term objective of Project 2 is to work collaboratively with CO-SCORE investigators to develop better strategies for treating and preventing the pathological consequences of gonadal aging, which disproportionately afflict women. 
     
  • Research Project 3: Sex hormones differentially regulate production of a distinct adipocyte population
    PI: Dwight J. Klemm, Ph.D.
    Co-Investigators: Kathleen M. Gavin, Ph.D., and T. Rajendra Kumar, Ph.D.

    The menopausal transition, an unavoidable aging-related phenomenon in women, is accompanied by increased abdominal adiposity and the concomitant incidence of adipose-related comorbidities. We have generated evidence that the cellular composition of adipose tissue (AT) defines the phenotype of each individual depot, determining its overall influence on metabolic health. The premise is that the loss of gonadal hormones alters the cellularity of AT, leading to changes in body fat distribution and worsening metabolic health. We previously discovered a novel lineage of adipocytes in the major white adipose depots of mice and humans generated from bone marrow–derived cells of the hematopoietic lineage rather than conventional mesenchymal precursors. In mice, bone marrow–derived adipocytes (BMDAs) were detected in greater numbers in abdominal fat depots and displayed increased inflammatory cytokine but decreased leptin and mitochondrial lipid oxidation gene expression, suggesting a critical role in influencing metabolic health. Furthermore, ovariectomy (OVX) significantly increased BMDA production, which was attenuated by estradiol (E2) replacement. In addition to declines in E2, menopause and OVX are also characterized by rising follicle-stimulating hormone (FSH) levels. Recent research questions whether the consequences of menopause traditionally attributed to the specific loss of ovarian E≠  may instead be caused by the previously unappreciated rise in FSH. Here we test the central hypothesis that E2 and FSH differentially regulate the production of BMDAs, altering the cellular composition of adipose tissue and resulting in significant changes in metabolic and inflammatory phenotype. Successful completion of these studies will define the roles of E2 and FSH in controlling the production of BMDAs, which may contribute to postmenopausal metabolic pathology. These data have the tremendous potential to highlight BMDA production as a new therapeutic target and provide novel strategies for the prevention of menopausal and aging-related chronic disease risk.

 

CAREER ENHANCEMENT CORE:
CEC Director:
Judith G. Regensteiner, Ph.D.  

 

The objectives of the CO-SCORE CEC are to develop and support a cadre of accomplished junior researchers in the thematic focus of the CO-SCORE, “Bioenergetic and Metabolic Consequences of the Loss of Gonadal Function,” and to provide a curriculum that meets the career enhancement needs of postdoctoral research fellows and junior faculty scientists focused on translational science in the study of women’s health and sex differences. The SCORE scholars will receive salary support to protect time for research and funds for research project support. In addition, meritorious pilot projects, selected through peer review, will be awarded to three promising scientists each year. SCORE scholars and pilot awardees will participate in an innovative career enhancement program, including team mentoring, hands-on research experience, and curricular training to cultivate academic skills and career development skills. Trainees will also participate in a summer course featuring relevant topics in endocrinology and receive training in methods and strategies for studying sex as a biological variable (SABV), which is being developed  by the SCORE faculty. SCORE scholars and pilot awardees will undergo training with the trainees in the Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) K12, the Colorado Clinical and Translational Sciences Institute (CCTSI) KL2 program, and the Center for Women’s Health Research (CWHR). The mentoring, research experience, and curricular training provided by this program will provide pivotal support for the SCORE scholars and pilot awardees as they develop careers in women’s health and sex differences research. Expanding the workforce in this area is critical to the field’s becoming fully realized. Success in this endeavor means that health and disease in women and men will be optimally studied so that medical research benefits everyone to the highest level possible.