There is a lack of funding for sex- and gender-based research due, in part, to insufficient awareness that conducting sexually dimorphic studies is critical to advancing knowledge that can lead to breakthrough discoveries effecting changes and improvements in clinical care across every medical discipline. To encourage more sex-based research, the Institute developed its Pioneer Awards program to provide investigators with seed funding ($25,000 each) who either currently study, or would like to initiate new research focusing on, the sex and gender determinants of health and disease. This cultivates a community of fellows and scholars invested in the study of sex-based research and medicine.
Specifically, this program:
- Enables early career investigators to conduct pilot studies that will help build their portfolio, thereby enhancing their ability to compete for large federal grants.
- Permits a senior investigator to explore a new and innovative research direction.
- Provides a mechanism for senior investigators to mentor young scientists who are interested in sex- based research that will support these young investigators to work in their clinic or lab.
- Advances our knowledge of women’s health through innovative research and a collaborative spirit that allows researchers to “think outside the box”.
Between 2007 and 2009, we supported 11 projects that have demonstrated the potential of this program to meet our original expectation and their results, as of October 2012, are impressive and listed below. Currently, we are not able to fund new Pioneer Grants but continue to search for funding opportunities. When they become available we will post a notice on this site.
Sleep in Women
Fred Turek, PhD, “The role of sex and aging in sleep-wake regulation and chronic partial sleep loss”
Dr. Turek’s lab discovered that hormone replacement restores sex differences in sleep observed in mice, in addition to demonstrating that the hormonal state of animals is critical to the sex differences observed in the responses to challenges such as stress or sleep deprivation. He also went on to find that disrupting the circadian rhythms has serious adverse pregnancy outcomes in mice that may have important implications for women with disrupted sleep rhythms who are trying to have a successful pregnancy. This funding trained several early investigators, one moved onto a career as Program Director at NIH, another is now professor at Morehouse School of Medicine. This work has generated pilot data for a larger proposal to the NIH, March of Dimes and Burroughs-Wellcome. (R03, RC1, March of Dimes and Burroughs Wellcome) and 2 fellowship proposals.
Publications generated by this project:
Paul KN, Losee-Olson S, Pinckney L, Turek FW. The Ability of stress to alter sleep in mice is sensitive to reproductive hormones. Brain Research. 19 Sept 2009.
Paul KN, Laposky AD, Turek FW. Reproductive hormone replacement alters sleep in mice. Neuroscience Letters. 463 (2009).
Summa KD, Vitaterna MH, Turek FW. Environmental Perturbation of the Circadian Clock Disrupts Pregnancy in the Mouse. PLoS ONE: Research Article, published 23 May 2012 10.1371/journal.pone.0037668
Peripheral Vascular Disease in Women
Melina Kibbe, MD, “The vasoprotective role of estrogen against cardiovascular disease”
Melissa Hogg, MD, “Women and the vasculature: Sex differences in vascular injury”
Demonstrated in rodents that sex and hormone status are important factors in evaluating vascular injury, neointimal hyperplasia, and the benefits of nitric oxide (NO)-based therapies. Male and female animals require different dosing of NO in order to inhibit neointimal hyperplasia, and this is likely attributable to differences between males and females at the cellular level This funding has changed the direction of Dr. Kibbe’s research, as her laboratory is now routinely studying the role of potential vascular therapies in both sexes. Dr. Kibbe was recently awarded a US Presidential Early Career Award for Scientists and Engineers.
Publications as a result or related to this research:
Hogg ME, , Vavra AK, Popowich DA, Banerjee MN, Martinez J. Jiang Q, Saavedra JE, Keefer LK, Kibbe MR. Effect of Nitric Oxide on neointimal hyperplasia based on sex and hormone status. Free Radic Biol Med. 2011 Jan 20.
Hogg ME, Vavra AK, Banerjee MN, Martinez J, Jiang Q, Keefer LK, Chambon P, Kebbe MR. The role of estrogen receptor a and b in regulating vascular smooth muscle cell proliferation is based on sex. J Surg Res. 2012 Mar. Epub 2011 Oct 8.
Infectious Disease in Women
Kimberly Scarsi, PharmD, MS, BCPS, “A population-based pharmacokinetic model of lopinavir/ritonavir concentrations in HIV-infected pregnant women”
The WHRI pioneer award was the first support used to develop a population based pharmacokinetic model in HIV-infected pregnant women, thus furthering our pharmacologic management of HIV-infected women. The pilot data generated is being combined with other institutions to build a robust model and drug assay and data analysis are ongoing. This award also substantially contributed to the PI’s growth as an investigator, providing a foundation for ongoing work in women’s health related to HIV pharmacology. Dr. Scarsi is currently co-chairing a multicenter trial through the AIDS Clinical Trials Group and recently received funding from the NICHD; both projects focus on women’s reproductive health choices by evaluating novel hormonal contraception in combination with antiretroviral therapy.
Minh Dinh, MD, “Evaluation of factors affecting HIV sexual transmission in men and women”
The vast majority of new HIV infections worldwide are a result of heterosexual transmission. Dr. Thomas Hope’s lab at Northwestern is known for a novel method of visualizing fluorescently labeled viral particles using epifluorescent microscopy. Dr. Dinh is using this technology to visualize individual HIV particles. Similarly, we are also developing an HIV transmission model in the male genital tract. Studies of both the female and male genital tract have demonstrated many similarities and differences between the various types of genital mucosal tissue. One of our aims is to evaluate the expression of various structural proteins in the genital tract mucosa. Characterizing the expression of these proteins in male and female genital epithelia will better outline the structural differences in the genital tissue.
These studies will be important for our understanding of how HIV is transmitted in the female genital tract and how certain women are at increased risk for HIV acquisition.
Publication as a result of this research:
Dinh MH, Ococha EA, Koons A, Veazey RS, Hope RJ. Espression of structural proteins in human female and male genital epithelia and implications for sexually transmitted infections. Biol Reprod. 2012 Feb 9.
Mental Health
Jackie Gollan, PhD, “Women’s mental health in pregnancy and the postpartum period: Creating a predictive index for postpartum depression”
Dr. Gollan wrote and issued a clinical protocol entitled “Standard of Care for Detection of Perinatal Depression” that serves as a guide for all Northwestern University-affiliated OB/GYN physicians in the Prentice Ambulatory Clinic, Northwestern Memorial Faculty Foundation, and Northwestern Memorial Physician’s Group to screen and triage patients who report perinatal depression.She also created a new clinic offering pharmacotherapy and psychotherapy for women who are pregnant or postpartum. She is developing the first model to examine the cognitive, affective, clinical and biological variables that contribute to the onset of depressive symptoms during the postpartum phase.
Publication Status:
Gollan JK, Hoxha D, Getch S, Sankin L, Michon R. Affective processing in pregnancy and postpartum with and without major depression. Psychiatry Research. Revise and resubmitted 10/1/12.
Gollan JK, Hoxha D, Sankin L, Getch S, Michon R. Locating Hostile Scenarios: Postpartum depression impairs spatial affect learning relative to healthy controls. Archives of Womens Mental Health. Submitted 7/29/12.
Neuroscience in Women
Catherine Woolley, PhD, “Development of an ERβ antibody to study estrogen and depression”
Dr. Woolley determined that all commercially available ERβ antibodies are not specific. Dr. Woolley is using these findings to alert the research community who has routinely used these reagents in publications and grant proposals that they can lead to incorrect conclusion due to faulty reagents.
Catherine Woolley, PhD, “Cryo-Immuno electon microscopy to study estrogen-sensitive vesicles”
She also discovered a novel new mode of estrogen action in the brain region important in learning and memory, anxiety/depression, and seizure activity in epilepsy. This work led a funded NIH, NIMH RO1 (MH095248-01), $1,931,250. A R21 is also pending.
Publications:
Smejkalova T, Woolley CS (2010) Estradiol acutely potentiates hippocampal excitatory synaptic transmission through a presynaptic mechanism. J. Neurosci. 30(48):16137-16148.
Snyder MA, Smejkalova T, Forlano PM, and Woolley CS (2010) Multiple ER antisera label in ER knockout and null mouse tissues. J. Neurosci. Meth. 188(2):226-234.“Cryo-Immuno electron microscopy to study estrogen-sensitive synaptic vesicles”
NOTE: And, Dr. Woolley’s lab found something that she thinks is even more important as a result of her work, which is the first sex-specific mechanism of synaptic modulation in a non-reproductive part of the brain supported by a different R01.
Publication:
Huang GZ, Woolley CS (2012) Estradiol acutely suppresses inhibition in the hippocampus through a sex-specific endocannabinoid and mGluR-dependent mechanism. Neuron 74(5):801-8
Heart Disease in Women
Martha Gulati, MD “Gender differences and temporal trends after stress testing”
As early as 1987, it was reported that 40% of male patients with an abnormal exercise radionucleotide test were referred for cardiac catheterization, in contrast with only 4% of the female patients. Gender differences in coronary catheterization referral have been demonstrated in a number of other studies, but the implications of the gender inequities are not clear. Certainly, the prevalence and presentation of CAD differs according to gender. In addition, the utilization and diagnostic value of stress tests differ according to gender as well.The goal of this pioneer award is to analyze the referral patterns for coronary angiography after any abnormal nuclear stress test, for both men and women, and determine is implications on mortality based on gender.
Obesity
Franck Mauvais-Jarvis, MD, PhD“Role of neonatal androgens in programming masculinization of energy homeostasis in women”
Today the prevalence of obesity, especially visceral obesity, is higher in women. Because of sex differences in evolutionary pressure, male and females have evolved specific ways to utilize and conserve calories and there are fundamental aspects of energy metabolism that are regulated differently in males and females. For example, males exhibit a more visceral adipose tissue distribution and they have lower serum levels of insulin sensitizing hormone adiponectin. Adiponectin is a critical anti-inflammatory adipocytokine promoting insulin sensitivity. The perinatal environment plays a crucial role in programming energy-balance set points and the role played by neonatal gonadal hormones in imprinting sex-dimorphic parameters of energy homeostasis is unknown. The goal of this project is to use the mouse model of neonatal androgenization to understand how the sex dimorphism observed in energy homeostasis is programmed using normal mice and mice lacking androgen receptors.
Publication:
Nohara K, Waraich R, Laque A, Tiano JP, Munsberg H, Mauvais-Jarvis F*. Early life exposure to testosterone programs the hypothalamic melanocortin system. Endocrinology. 2011 Apr;152(4):1661-9. Epub.2011 Feb 8.
Bone Health
Paula Stern, PhD “Skeletal Effects of Estrogen and Androgen”
The goal of the research is to elucidate the differences in the effects of estrogen and androgen on bone by determining the actions of both hormones on the cell types responsible for the formation and breakdown of bone. Estrogen and androgen are critical for maintenance of bone in both males and females. Studies in mouse models suggest that the cellular mechanisms by which androgens and estrogens protect bone are dissimilar, with estrogens having multiple actions on osteoblasts and on osteoblast survival, and androgens action being directly on the osteoclast.
The proposed research will determine responses of human osteoblasts and osteoclast precursor cells from male and female donors to estrogen and androgen using real time PCR microarray. An understanding of the differences in responses to the two hormones in females and males should lead to more appropriate care.. The findings indicate that although osteoclasts from both sexes respond to 17β-estradiol and testosterone, the effects of both 17β-estradiol and testosterone differ in the two sexes, highlighting the importance of considering gender in the design of therapy.
Publication:
Wang J, Stern PH. Sex-specific effects of estrogen and androgen on gene expression in human monocyte-derived osteoclasts. J Cell Biochem. 2011 Dec.