CENTER FOR HEALTHY AGING IN WOMEN
Our Mission
The Buck Center for Healthy Aging in Women is spearheading a paradigm shift in women's health research. While women outlive men by a few years on average, they also experience a disproportionately longer period of poor health. We're dedicated to understanding and enhancing women's health by focusing on a critical yet overlooked aspect of female physiology: ovarian function. Ovaries are the architects of health and the pacemakers for aging in female bodies. They age faster than other organs, leading to wide-ranging health implications. The consequences extend far beyond fertility and menopause, impacting women’s health through their entire adult lives. Our mission is to extend ovarian health to improve female healthspan, addressing a fundamental inequality in medical research and healthcare.
Since our inception in 2019, we pioneered a completely new area of research at the interface of longevity science and reproductive biology. Our Center is a novel innovation hub with a global anchor - the Productive Health Global Consortium - that is growing a sustainable, impactful, and diverse ecosystem to accelerate translation, raise awareness, address gaps in knowledge, develop targeted treatments, and improve health outcomes for aging women worldwide.
Our Groundbreaking Research
We're creating the first-ever comprehensive map of the ovaries across space and time – an ambitious project that will transform our understanding of women's health and aging. Here's how we're making this happen:
Seeing the Unseen: Using cutting-edge imaging technologies, we're creating detailed 3D maps of ovarian structure that reveal previously hidden features. This allows us to see how different cell types communicate and function together. We're also mapping the intricate network of blood vessels, nerves, and lymphatic vessels that support ovarian function, using advanced tissue clearing techniques that make organs transparent for detailed 3D imaging.
Pioneering New Solutions; We're developing groundbreaking biomarker and diagnostic tools, ovary tissue models, and exploring novel techniques that measure early warning sign of aging. Through this work, we're identifying specific factors produced by young, healthy ovaries that could someday be used therapeutically to extend healthy aging in females. Our research into cellular aging (senescence) is revealing how ovaries age differently from other organs. We're studying the role of NAD+, a crucial molecule that declines with age, and how it affects egg cell quality and quantity. By examining extraordinary examples from nature – like whales who can reproduce into their 90s – we're uncovering clues about what drives ovarian aging.
Understanding the Whole System: Our research reveals the complex relationships between ovarian function and whole-body health. We're mapping how ovarian hormones influence body fluid balance and studying the previously unknown role of the lymphatic system in ovarian function. Using sophisticated single-cell genetic sequencing and advanced microscopy techniques, we can now track thousands of molecular changes that occur during ovarian aging. By integrating these findings with data on how social and economic factors affect menopause experiences across different populations, we're developing a comprehensive understanding of ovarian health that will lead to more effective, personalized treatments for women worldwide.
CENTER DETAILS
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Malene Hansen, PhD Steering Committee Member -
Eric Verdin, MD Steering Committee Member -
Francesca Duncan, PhD Steering Committee Member
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Julie Andersen, PhD Professor, Buck InstituteThe Andersen lab studies sex-specific neurogenerative mechanisms. Recently, ApoE4 was identified as the strongest genetic risk factor for Lewy body dementia (LBD) in women. However, it is not yet understood how ApoE4 interacts with known environmental risk factors to contribute to the disorder. The Andersen lab seeks to determine the impact of oral iron intake mimicking that found in drinking water and diet on sex-specific progression of ApoE4-associated LBD to identify potential treatment options, including prophylactic dietary interventions or iron chelation therapies for genetically susceptible women.
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Chris Benz, PhD Professor, Buck InstituteThe Benz lab has long been at the forefront of women’s health studies. Benz was the co-founder of the Marin Women’s Study, whose molecular epidemiologic findings first identified a common IGF1R gene variant associated with later life protection from breast cancer. Since that seminal publication, the lab has been studying the molecular underpinnings of late-life cancers and cardiovascular disease in women. The lab is also investigating aging and cell senescence as it occurs in a woman’s breast across her lifespan, how that relates to her later life risk for breast cancer as well as metabolic and cardiovascular diseases.
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Francesca Duncan, PhD Assistant Professor in ResidenceThe Duncan lab is focused on understanding how the aging ovarian microenvironment changes with age and impacts egg quality and quantity and endocrine function. They made the fundamental observation that the aging ovary becomes inflammatory, fibrotic, and stiff with age, and this has significant ramifications for egg development, ovulation, and even ovarian cancer pathogenesis. Their research is now focused on translating these observations into novel biomechanical and matrix biomarkers of ovarian aging as well as therapeutic strategies preventing or reversing fibrosis to extend reproductive longevity.
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Deena Emera, PhD Senior Scientist and Writer in ResidenceThe Emera lab uses evolutionary insights to address problems in women’s health. Past work has focused on the evolution of the mammalian endometrium and implications for pregnancy and menstruation in humans. Current work is focused on the evolution of reproductive longevity in long-lived mammals such as baleen whales, in an effort to promote ovarian and overall health in humans.
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David Furman, PhD Associate Professor, Buck InstituteThe Furman lab is investigating the role of menopause and hormone replacement therapy (HRT) on health outcomes. While HRT is commonly prescribed for menopausal symptoms, its use remains controversial following studies associating HRT with elevated risk of adverse events such as breast cancer, stroke, and blood clots. The Furman lab has developed blood-based models to predict the biological age of 9 physiological systems, including circulatory, musculoskeletal, and respiratory. These models are being employed to investigate the organ specific impact of menopause, and the benefits and risks of HRT. This work allows for the possibility of a more precision-based approach to HRT use and the overall treatment of menopausal symptoms that maximizes therapeutic efficacy while minimizing poor outcomes.
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Malene Hansen, PhD Chief Scientific Officer and Professor, Buck Institute
The Hansen lab studies the cellular recycling pathway called autophagy, and how this conserved process regulates germ cell maintenance and fertility, using the short-lived and genetically tractable nematode C. elegans. They also examine how environmental stresses, such as nutrient deprivation and heat stress modulate autophagic activity in germ cells and surrounding somatic gonad cells, as well as inter-tissue connectivity. Because the core autophagy machinery is highly conserved from worms to humans, insights from C. elegans could reveal fundamental principles of reproductive health and age-related fertility decline in people.
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Pankaj Kapahi, PhD Professor, Buck InstituteThe Kapahi Lab explores how key biological processes, like puberty and pregnancy, impact aging in women. Their research also examines biological mechanisms of menopause and how cellular senescence contributes to aging in the ovaries. By studying different models, including flies, mice, and human data, they aim to uncover universal mechanisms that connect reproductive stages and aging in women, helping us better understand women’s health across their lifespan.
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Bikem Soygur Kaya, PhD Reproductive Biology Hub DirectorThe Repro Hub investigates how the lymphatic vasculature influences ovarian function and aging. The ovary’s unique physiology places exceptional demands on the lymphatic system, and aging ovaries often show increased inflammation and fibrosis—changes closely tied to impaired lymphatic function. Using advanced 3D imaging technologies, the Hub explores the structure and function of lymphatic vessels in the context of ovarian biology and reproductive aging.
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Jennifer Lovejoy, PhD Transitional and Behavioral Scientist, Phenome Health Visiting Scientist, Buck InstituteClinical research by Lovejoy and colleagues has addressed sex differences in obesity, as well as the effect of sex hormones on cardiometabolic and behavioral risks. Her group conducted a large NIH-funded longitudinal study of the menopausal transition, identifying key metabolic and behavioral risk factors that change from pre- to post-menopause in African-American and Caucasian women. More recently, Lovejoy has focused on developing intervention protocols for lifestyle management of menopausal symptoms and postmenopausal health risks based on multiomic data. With other clinical collaborators at Buck, she is developing a study using multiomic data to predict subtypes in early menopausal women to guide personalized interventions, as well as a study examining the impact of the menstrual cycle on multiomic, behavioral and environmental measures.
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Nathan Price, PhD Professor, Buck Institute; Co-Director, Center for Human HealthspanThe Price lab works to advance the frontiers of maternal health and pregnancy research. They leverage multi-omics technologies to unravel complex biological pathways that underpin healthy pregnancies and identify early indicators of potential complications. Their work has helped uncover specific biomarkers that can predict the risk of preterm birth, enabling earlier and more personalized interventions. They have also investigated the impact of maternal SARS-CoV-2 infection on birth outcomes, emphasizing the importance of monitoring and preventive care during pregnancy. By integrating molecular data from thousands of individuals, they are developing predictive models that personalize care for mothers and optimize health outcomes for both mother and child. These discoveries illuminate how maternal health sets the foundation for long-term well-being.
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Birgit Schilling, PhD Director, Proteomics Core and Professor, Buck InstituteThe Schilling lab has several ongoing projects to determine protein biomarkers for the aging human ovary, and in collaboration with the Duncan lab, has developed a human explant ovary model (growing primary human ovary tissue in the lab) to develop future therapeutic interventions. The lab is also investigating racial disparities during ovarian aging and providing analytical methods to understand underlying mechanistic differences. Recent technologies now allow for spatial mass spectrometric imaging of proteins, metabolites, lipids and glycans in the aging human ovary generating deep multi-molecular maps. Additionally, in collaboration with researchers at Johns Hopkins University, they developed the growth of human fallopian tubes in the lab as so called ‘assembloids’ where we they can simulate the different tissue compartments and complex microarchitecture of women’s fallopian tubes and even induce function of moving oocytes. Understanding molecular changes of proteins during changes in the ovary or fallopian tubes will be crucial for future therapeutic interventions to improve women’s health overall.
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Ashley Webb, PhD Associate Professor, Buck InstituteThe Webb lab is currently investigating the mechanisms of female brain aging. They recently made the intriguing discovery that genes on the X chromosome are particularly susceptible to changes with age in neurons of the female hypothalamus, a brain region critical for physiological homeostasis and women’s health. The lab’s ongoing work investigates the molecular mechanisms by which the X chromosome is impacted with age in the female brain and the implications of these changes for healthy aging and vulnerability to neurodegeneration in women.
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Eric Verdin, MD Professor, President and CEO of Buck Institute
The Verdin lab is studying the role of NAD metabolism in ovarian biology. They have established and published on a novel role of CD38 in regulating ovarian NAD+ metabolism and establishing and maintaining the ovarian reserve, a critical process that dictates female reproductive lifespan. They are also studying the role of the mitochondrial fission factor (MFF) in female fertility. MFF levels decrease in the ovary during aging and MFF knockout mice exhibit central hypogonadism. They are exploring novel therapeutic interventions targeting this pathway.
Ongoing Research in the Center to Map Ovaries Across Time and Space:
Cellular Senescence Network: NIH Common Fund’s Cellular Senescence Network (SenNet) Program was established to comprehensively identify and characterize the differences in senescent cells across the body, across various states of human health, and across the lifespan. Buck is a site for mapping the frequency of senescent cells in the cycling and post-menopausal ovary (Duncan, Melov, Schilling labs and Reproductive Biology Hub collaboration).
Delineating the role of NAD+ metabolism in establishing the ovarian reserve, a critical process that dictates a female’s reproductive lifespan (Verdin lab, Duncan lab, and Reproductive Biology Hub collaboration).
Understanding the role of mitochondrial function in female fertility (Verdin lab and Reproductive Biology Hub collaboration, supported in part by a Buck ProductiveHealth grant).
Developing a new mammalian menopause model: Pallas’s long-tongued bat (Garrison lab).
Discovery of rejuvenating factors made by human ovaries (Garrison lab).
How race, societal, and economic factors impact the severity of peri/menopause symptoms (Garrison lab).
3D analysis of the lymphatic system in the cycling and aging ovary (Soygur-Kaya and the Reproductive Biology Hub).
Targeting fibrosis and inflammation to extend ovarian function (Duncan lab through a Buck ProductiveHealth grant).
Adapting shear wave elastography ultrasound to assess ovarian stiffness across the reproductive lifespan as a non-invasive biomarker of ovarian aging (Duncan lab through a Buck ProductiveHealth grant).
Building a human explant ovary model to develop future therapeutic interventions (Duncan and Schilling lab collaboration).
Studying the genetic basis of menopause in exceptionally long-lived mammals (whales!) (Emera through a Buck ProductiveHealth grant).
Mapping peripheral nerve innervation of the ovaries to understand how the autonomic nervous system impacts ovarian aging (Haghighi lab through a Buck ProductiveHealth grant).
Impact of ovarian hormones on fluid balance, dehydration, delirium, and susceptibility to urinary tract disorders during aging (Garrison lab).
Using spatial transcriptomics and 3D tissue clearing to map the cycling and aging ovary (Garrison lab).
Understanding how CSF (cerebrospinal fluid) production in the brain may be controlled by ovaries; impact on aging and Alzheimer’s disease prevalence in females (Garrison and Lishko lab collaboration).
Between 2020 and 2023, the Global Consortium for Reproductive Longevity and Equality (GCRLE) catalyzed scientific advancement on a global scale. Administered through the Buck Institute, $14.5 million in funding supported 50 investigators around the world to fuel new discoveries in ovarian aging and longevity.
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2020 GCRLE GRANTEESHolly Ingraham, PhD, Senior Scholar Award Recipients
University of California, San Francisco
Identifying Novel Drivers in Central Control of Female ReproductionListen to Dr Ingraham discuss her research in OVA Hour | Episode 9
Listen to Dr Ingraham present her research in Making Reproductive Longevity a Reality | Episode 2 -
Coleen Murphy, PhD Senior Scholar Award RecipientPrinceton University
Defining a “Clock” for Female Reproductive DeclineListen to Dr Murphy present her research in Making Reproductive Longevity a Reality | Episode 1
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Mary Zelinski, PhD Senior Scholar Award RecipientOregon Health & Science University
Interventions for Ovarian AgingListen to Dr Zelinski present her research in Making Reproductive Longevity a Reality | Episode 9
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Bérénice Benayoun, PhD Junior Scholar Award RecipientUniversity of Southern California
Establishing new age-relevant mouse models of menopauseListen to Dr Benayoun present her research in Making Reproductive Longevity a Reality | Episode 4
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Lynae Brayboy, MD Junior Scholar Award RecipientCharité – Universitätsmedizin, Berlin
Dysfunctional MDR-1 disrupts mitochondrial homeostasis in the oocyteListen to Dr Brayboy present her research in Making Reproductive Longevity a Reality | Episode 7
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Ingrid Fetter-Pruneda, PhD Junior Scholar Award RecipientUniversidad Nacional Autónoma de México
The molecular and cellular basis of high fecundity in social insectsListen to Dr Fetter-Pruneda present her research in Making Reproductive Longevity a Reality | Episode 4
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Amanda Kallen, MD Junior Scholar Award RecipientYale University
Ovarian Senescence as a Novel Driver of Female Reproductive AgingListen to Dr Kallen present her research in Making Reproductive Longevity a Reality | Episode 5
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Ivana Celic, PhD Pilot Award RecipientTulane University
LINE1 Retrotransposons in Female Reproductive AgingListen to Dr Celic present her research in Making Reproductive Longevity a Reality | Episode 3
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Iain Cheeseman, PhD Pilot Award RecipientWhitehead Institute, MIT
Analyzing centromere rejuvenation during female reproductive agingListen to Dr Cheeseman present his research in Making Reproductive Longevity a Reality | Episode 6
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Marco Conti, MD Pilot Award RecipientUniversity of California, San Francisco
mRNA translation program and oocyte agingListen to Dr Conti present his research in Making Reproductive Longevity a Reality | Episode 8
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Arjumand Ghazi, PhD Pilot Award RecipientUniversity of Pittsburgh
Genetic & Chemical Modulation of Splicing to Combat Reproductive SenescenceListen to Dr Ghazi present her research in Making Reproductive Longevity a Reality | Episode 5
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Polina Lishko, PhD Pilot Award RecipientUniversity of California, Berkeley
Endocannabinoid signaling in the mammalian ovary and reproductive longevityListen to Dr Lishko present her research in Making Reproductive Longevity a Reality | Episode 2
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Zita Santos, PhD, Carlos Ribeiro, PhD Pilot Award RecipientsFundação D. Anna de Sommer Champalimaud e Dr. Carlos Montez Champalimaud
Metabolic reprogramming, dietary nutrients and food cravings in ovary agingListen to Dr Ribeiro and Dr Santos present their research in Making Reproductive Longevity a Reality | Episode 3 and Episode 8
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Yousin Suh, PhD Pilot Award RecipientColumbia University
Genetic Control of Ovarian Aging in Humans -
Cristina Quesada Candela, PhD Postdoctoral Scholar Award RecipientMagee-Women’s Research Institute and Foundation
University of Pittsburgh
Proteasomal Targets Driving Meiotic Failure During Reproductive Aging -
Ana Milunovic Jevtic, PhD, DVM Postdoctoral Scholar Award RecipientUniversity of California, Berkeley
The role of endocannabinoid hydrolase ABHD2 in the ovarian aging -
Bikem Soygur, PhD Postdoctoral Scholar Award RecipientUniversity of California, San Francisco
How duration of meiotic prophase affects development and aging of oocytesListen to Dr Gul Soygur Kaya present her research in Making Reproductive Longevity a Reality | Episode 6
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Min Hoo Kim, PhD Postdoctoral Scholar Award RecipientUniversity of Southern California
Elucidating causal effects of the microbiome on reproductive agingListen to Dr Kim present her research in Making Reproductive Longevity a Reality | Episode 7
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Seungsoo Kim, PhD Postdoctoral Scholar Award RecipientColumbia University
Integrative bioinformatic analysis of human ovarian aging and healthspan -
Olfat Malak, PhD Postdoctoral Scholar Award RecipientBuck Institute for Research on Aging
Role of sympathetic transmission in the regulation of ovarian aging -
Farners Amargant i Riera, PhD Postdoctoral Scholar Award RecipientNorthwestern University
Targeting fibrosis and inflammation to extend reproductive longevityListen to Dr Amargant present her research in Making Reproductive Longevity a Reality | Episode 9
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Zijing Zhang, PhD Postdoctoral Scholar Award RecipientUniversity of Arkansas for Medical Sciences
The impact of ovarian macrophage population on mouse ovarian aging -
2023 GCRLE GRANTEES Junior Scholar Award RecipientMiguel Angel Brieño- Enríquez, MD, PhD
University of Pittsburgh
Natural partial reprograming in the naked mole-rat ovary leads to ovarian rejuvenation and protracted fertility -
Longhua Guo, PhD Junior Scholar Award RecipientUniversity of Michigan
Molecular and genetic drivers of female reproductive aging and rejuvenation -
Sarah Ocanas, PhD Junior Scholar Award RecipientOklahoma Medical Research Foundation
Comparison of macrophage activational response to immunomodulatory and hormonal signaling in the female mouse brain and ovary with reproductive aging. -
Diana Laird, PhD Senior Scholar Award RecipientUniversity of California, San Francisco
The aging of human follicles: a molecular portrait and 3D landscape -
Michael Stout, PhD Senior Scholar Award RecipientOklahoma Medical Research Foundation
Unraveling how mTORC1 activity in stromal fibroblasts contributes to ovarian inflammation, cellular senescence, fibrosis, & follicular exhaustion -
Elvan Böke, PhD Pilot Award RecipientCentre for Genomic Regulation
Deciphering cell-intrinsic and cell-extrinsic mechanisms of oocyte ageing -
Iain Cheeseman, PhD Pilot Award Recipient
Whitehead Institute for Biomedical Research
Analyzing mRNA splicing as a source of reduced oocyte quality during female reproductive aging -
Hattie Chung, PhD Pilot Award RecipientBroad Institute of MIT and Harvard
Profiling the spatiotemporal dynamics of cellular diversity during ovarian aging -
Aubrey Converse, PhD, Michele Pritchard, PhD Pilot Award RecipientNorthwestern University
Macrophage-derived multinucleated giant cells as drivers of aging in the mammalian ovary -
Francesca Duncan, PhD Pilot Award RecipientNorthwestern University
Shear wave elastography (SWE) in assessment of human ovarian stiffness and reproductive longevity -
Deena Emera, PhD Pilot Award RecipientBuck Institute for Research on Aging
The genetic basis of reproductive longevity in exceptionally long-lived mammals -
Michael Garratt, PhD, Rebecca Campbell, PhD, and Greg Anderson, PhD Pilot Award RecipientUniversity of Otago
Uncoupling nutrition from reproduction to extend female fertility -
Arjumand Ghazi, PhD Pilot Award RecipientUniversity of Pittsburgh
Defining a Molecular Signature of Aging Induced by Gonadal Dysfunction -
Kathryn Grive, PhD Pilot Award RecipientWomen’s and Infants Hospital of Rhode Island
Revealing the Role of Ubiquitin C-Terminal Hydrolase L1 and the Ovarian Proteasome Pathway in Female Reproductive Aging -
Zachary Knight, PhD Pilot Award RecipientUniversity of California, San Francisco
Effect of reproductive aging on the gut-brain axis -
T Rajendra Kumar, PhD Pilot Award RecipientUniversity of Colorado
Re-routed FSH Secretion and Female Reproductive Longevity -
Lena Pernas, PhD Pilot Award RecipientUniversity of California, Los Angeles
Identification of novel regulators of steroidogenesis -
Augusto Schneider, PhD Pilot Award RecipientUniversidade Federal de Pelotas
BCAAs regulate ovarian aging in response to diet composition and exercise -
Olga Bielska, PhD Postdoctoral Scholar Award RecipientBuck Institute for Research on Aging
Uncovering a new gene linking aging, mitochondria, and infertility -
Hannes Campo, PhD Postdoctoral Scholar Award RecipientNorthwestern University
Development of a vascularized microfluidic ovarian senescence model for senolytic drug screening. -
Haiyuan Mu, PhD Postdoctoral Scholar Award RecipientUC Berkeley
Regulation and functional roles of retrotransposon in ovarian aging -
Yasuhisa Munakata, PhD Postdoctoral Scholar Award RecipientUniversity of California, Davis
Chromatin regulatory mechanisms of ovarian reserve underlying disrupted gene expression in aged oocytes -
Periklis Paganos, PhD Postdoctoral Scholar Award RecipientMarine Biological Laboratory
Gene regulatory networks controlling sea star reproductive longevity and aging -
Na-Young Rho, PhD Postdoctoral Scholar Award RecipientYale University
Determining Molecular Pathways in Human Ovarian Aging -
Laura Wester, PhD Postdoctoral Scholar Award RecipientMax Planck Institute for Biology of Ageing
Translating the translatome: How reproductive quiescence and activation are regulated by mRNA translation-based mechanisms in Caenorhabditis elegans
IN THE NEWS
Beyond fertility and menopause: See why the ovary is central to women’s health and longevity
Reproductive revolution
Buck Institute in Novato gets $6 million grant to study negative health effects from menopause
