Harvard Catalyst Profiles

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Jill M. Goldstein, Ph.D.

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Brown University , Providence, RIA.B.05/1976Psychological Anthropology
Columbia University School of Public Health, NY, NYM.P.H05/1979Mental Health Evaluation
Columbia University Graduate School of Arts and Sciences, NY, NYPh.D.05/1985Epidemiology in Psychiatry
Harvard Medical School, Beth Israel & Massachusetts General Hospitals, Boston, MAPostdoctoral05/1994Clinical Neuroscience
Harvard University, Cambridge, MAHonorary M.A.2004In Honor of Harvard Professorship
1987 - 1989
Schizophrenia Research Program Award
1989 - 1989
NIMH Young Investigator Award
1989 - 1991
Young Investigator Award for Scientific Research
1990 - 1991
William F. Milton Fund Award for Scientific Research
1991 - 1992
NIMH Clinical Research Fellowship Award in Biological Psychiatry
2002 - 2003
Collaborative Research Award
2005 - 2005
Award for Exploratory Seminar on the “Genetics of Sex Effects in Clinical Medicine”
2007 - 2007
Selected the 2007 Spinoza Professor
2008 - 2008
Award for Exploratory Seminar on “Unexplored Sex Differences in Cardiovascular Disease”
2013 - 2013
Stuart T. Hauser Mentorship Award in Psychiatry
2015 - 2015
Distinguished Scientist Award
2015 - 2015
Award for Workshop entitled "Sex-Dependent NeuroDiscovery and CNS Therapeutics"
2018 - 2018
Award for Women, Heart and Brain Global Initiative Stakeholders Meeting
Helen T. Moerschner Endowed MGH Research Institute Chair in Women's Health
Founder and Executive Director of the Innovation Center on Sex Differences in Medicine

Introduction: I have had a long-standing interest in sex differences in the brain and the roles of steroid hormones, genes, and markers of immune function in understanding sex differences in psychiatric disorders and their comorbidity with general medicine. I believe that an understanding of these pathways will provide knowledge for the development of novel sex-dependent therapeutic discovery. For >30 years at Harvard, I have been working with colleagues that span Harvard schools and departments and other collaborative institutions that integrate fields of study, methods of analysis, and levels of study from basic to clinical to tackle issues of sex differences in medicine and women's health. Relatively little is known about how sex differences in healthy brain development may or may not deviate in producing pathology and the impact on treatment. Further, clinical decisions based on research are primarily based on data from males that are often inappropriate for females, even for disorders (like depression) in which women predominate. Given the gap between the clinical and scientific importance of studying sex effects in medicine and the relative paucity of studies on these issues, the history of my work has contributed to moving this field forward.

History of Research: My laboratory, called the Clinical Neuroscience Laboratory of Sex Differences in the Brain, has been ongoing for >25 years (http://cnl-sd.mgh.harvard.edu). Our team consists of an interdisciplinary group of investigators, integrating structural and functional MRI studies, psychophysiology, steroid hormones, markers of immune function, genetics, and collaborative efforts with preclinical investigators modeling steroid hormones, genes, immune function, and the brain. The first disorder of interest was schizophrenia, a devastating illness for which men have a higher risk than women. Although in the 1980’s, the prevailing ideology was that it was similar in men and women, my team was instrumental in demonstrating that men have a significantly higher risk than women, the causes for which begin during mid-gestation, a key period of the sexual differentiation of the brain. Our studies of sex differences in cognitive functions identified specific domains in which women compared with men had relative preservation of function, i.e. language, executive functions, verbal memory, and olfaction. Using structural and functional MRI, my team identified brain abnormalities in schizophrenia in regions associated with sex differences in cognitive and affective functions. These brain regions, rich in gonadal hormone receptors, led to studies with basic neuroscience colleagues to map out prenatal stress and immune mechanisms associated with the dysregulation of the sexual differentiation of the brain during mid-gestation. We further demonstrated similar causal pathways for understanding sex differences in the risk for major depressive disorder, but for which women have a significantly higher risk than men.

Over the last 15 years, the lab has focused on sex differences in major depression and why it is highly comorbid with cardiovascular disease and risk for Alzheimer’s disease later in life. We continue to take a lifespan approach to understanding sex differences in the shared causes of these disorders of the heart and brain. Included in this work, I oversee a unique prenatal cohort study in which subjects have prospective data from pregnancy through their 60’s, including brain imaging, allowing us to investigate in a human population the fetal programming of adult onset disorders, a topic primarily studied in animals. Our work has contributed to identifying fetal stress-immune biomarkers that disrupt the sexual differentiation of the brain and that are retained and expressed in adulthood as sex differences in deficits in stress response circuitry, major depression, and comorbid physiologic and cardiac dysfunction. In 2018, I launched the Innovation Center on Sex Differences in Medicine (ICON), a collaborative effort between Massachusetts General Hospital and the Harvard T. H. Chan School of Public Health, partnering with WomenAgainstAlzheimers (http://icon.mgh.harvard.edu). ICON consists of collaborators across departments, fields and methodologies bringing together psychiatry, OB-GYN, cardiology, neurology, and public health. ICON’s primary mission is to leverage fundamental discoveries “from cells to society” about sex differences in the brain and heart into strategies to develop sex-dependent therapeutics and target them early for prevention. In addition, we are invested in educating the next generation of scientists, clinicians, and the public about sex differences in medicine and advocating for these issues at the national and global levels. In 2020, ICON was designated an NIH Specialized Center of Research Excellence (SCORE) for Sex Differences in Medicine, one of only 8 in the country.

Finally, I have spent my career educating the next generation of scientists and clinicians to study sex differences in health and disease across disciplines and methods and providing resources for their careers in women’s health and sex differences in medicine. In the service of this for >15 years, I have been the PI of a Harvard-wide junior faculty training program (ORWH-NICHD K12 HD051959-06) called Building Interdisciplinary Careers in Women's Health (BIRCWH) with ours targeted to "Hormones and Genes in Women's Health: From Bench to Bedside". With a translational focus, BIRCWH is training the next generation to investigate sex differences in medicine, and/or women's health specifically, and incorporate the knowledge into their academic and clinical careers in medicine.

The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. RF1AG074008 (GOLDSTEIN, JILL M) Sep 30, 2021 - Aug 31, 2024
    Impact of sex differences in immune function on shared risk for cardiometabolic disorder & Alzheimer's disease
    Role: Principal Investigator
  2. U54MH118919 (GOLDSTEIN, JILL M) Feb 1, 2020 - Dec 31, 2024
    Sex Differences in Major Depression: Impact of Prenatal Stress-Immune and Autonomic Dysregulation
    Role: Principal Investigator
  3. R01AG067019 (GOLDSTEIN, JILL M) Sep 15, 2019 - May 31, 2025
    Impact of Depression on Alzheimer's disease: Prenatal Immune Origins and Shared Impact of Sex
    Role: Principal Investigator
  4. R01AG057505 (GOLDSTEIN, JILL M) Jun 15, 2018 - Feb 28, 2029
    Aging of Emotion Circuitry: Impact of Sex, Depression, and Fetal Immune Origins
    Role: Principal Investigator
  5. R56MH113217 (GOLDSTEIN, JILL M) Sep 20, 2017 - Aug 31, 2018
    Prenatal Immune Programming of Sex Differences in Dysregulation of Emotion Processing in Midlife
    Role: Principal Investigator

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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.