MORE-WH Program

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Maryland's Organized Research Effort in Women's Health(MORE-WH), 2002-2007

NIH K-12 BIRCWH II (Building Interdisciplinary Research Careers in Women's Health) Program

Program Overview

The Women's Health Research Group was awarded a five-year (9/26/02-7/31/07) NIH BIRCWH (Building Interdisciplinary Research Careers in Women's Health) grant to train faculty-level scholars to conduct interdisciplinary research in women's health. The WHRG program, called Maryland's Organized Research Effort in Women's Health (MORE-WH), provides opportunites for individuals in the early stages of their research careers to work with experienced faculty scientists from a variety of different disciplines. The University of Maryland, Baltimore is an ideal training environment because of the strong basic, clinical and epidemiological research in women's health currently being conducted in four of the seven professional schools (dentistry, medicine, nursing and pharmacy) on the UMB campus.

Principal Investigator: Patricia Langenberg, Ph.D., plangenb@umaryland.edu
Program Director: Istvan Merchenthaler, M.D., Ph.D., D.Sc., imerchen@epi.umaryland.edu

Program Description and Aims

The MORE-WH (Maryland's Organized Research Effort in Women's Health) Program will provide tailored research training in women's health to up to eight junior faculty scholars (half with clinical doctorate degrees and half with Ph.D's) over the next five years. Qualified individuals will be offered faculty positions with 75% released time in the department/professional school most closely related to their area(s) of research interest. To meet each scholar's specific needs, a personalized career plan, to include didactic coursework and performance of mentored research in the laboratory or research program of an established investigator, will be developed for each scholar. An interdisciplinary team will be assembled to provide additional expertise and guidance in areas relevant to the scholar's own research interests. Appointments will be made for January 1st and July 1st start dates. The minimum appointment is for two years renewable in yearly increments until the scholar has established research independence and is qualified to compete for NIH-sponsored grants.

Scholars will be evaluated periodically based on the training and research goals established in their own personalized career development plans. Each plan will establish milestones for publications, grant submissions/funding, and scientific presentations. Scholars will also be evaluated on successful completion of didactic coursework and participation at seminars, journal clubs, and other educational programs.

The specific aims of the MORE-WH program are:

To identify and recruit outstanding new investigators who wish to pursue careers in women's health research;
To provide these new investigators with individually-tailored training experiences that take advantage of the strong existing basic, clinical and epidemiological research base in women's health and the interdisciplinary institutional research infrastructure at UMB; and
To increase the number of researchers working nationally in the area of women's health.

Research Themes and Lead Mentors

UMB Faculty selected to be Lead Mentors for the MORE-WH Program actively conduct and collaborate on interdisciplinary projects that focus on a number of areas relevant to women's health. These are grouped together into three broad research themes:

Life Changes in Women's Health (from development to post-menopause)
Adverse Conditions and Diseases in Women
Gender Differences in Pain

These areas span traditional and emerging research in reproductive epidemiology, clinical medicine, and basic scientific research, and will provide a variety of opportunities for MORE-WH scholars to gain basic and specialized skills.

Life Changes in Women's Health

This research theme draws on our strengths in research on female reproduction from basic science, clinical, and epidemiological perspectives. Mentors are conducting research that concentrates on all aspects of female reproduction from development of the reproductive tract to menopause and beyond. Such research includes studies on the development of the ovary and brain, ovarian function from embryonic life through menopause, the effects of growth factors and steroid hormones on reproductive tissues, the effects of steroid hormones on pregnancy, the physiological changes that occur as women transition from reproductive life to menopause, and the risks and benefits of therapies used to treat menopausal women. Normal development of the ovary and brain is essential for several aspects of reproduction including cyclicity, fertility, and sexual behaviors. To study the Development phase of reproduction, Dr. Eugene Albrecht uses a multidisciplinary approach to determine the factors regulating maturation of the placenta and steroidogenesis in the maternal/fetal ovary. Dr. Margaret McCarthy uses molecular, cellular, and morphologic techniques to examine the factors that regulate brain differentiation and neurochemistry and to determine how these factors in turn regulate a myriad of sex differences in the adult. Dr. Jodi Flaws uses molecular and epidemiological approaches to identify whether members of the bcl-2 family of proto-oncogenes regulate the development of the mammalian ovary.Dr. Robert Koos utilizes molecular and cellular techniques to examine whether growth factors and their receptors are important for development of the rodent ovary.

During the Reproductive Years, normal ovarian function is required for the development of fertilizable oocytes, menstrual/estrous cyclicity, and the synthesis and secretion of hormones, including estrogens, androgens, and progestins. These hormones play an important role in regulating and maintaining the female reproductive system. The laboratories of Dr. Gloria E. Hoffman and Dr. Michael Selmanoff explore the neural mechanisms underlying negative and positive feedback effects of estrogen on the reproductive system. They also examine the factors required for the regulation of prolactin secretion. The goal of Dr. Robert Koos' research is to understand the mechanisms that control angiogenesis in the follicle and corpus luteum (CL) of the ovary and the endometrium of the uterus. A multidisciplinary approach is used in Dr. Eugene Albrecht's laboratory to study the developmental regulation of placental and fetal growth, maturation, and function in primates.

The Menopausal Transition is a critical event in the lives of most women. It is associated with a decline in ovarian function, significant changes in the quality of life, and alterations in the risk of chronic diseases such as osteoporosis and depression. Despite the importance of this transition, little is known about the factors that regulate the menopausal transition. To increase our knowledge about this transition, several investigators in the Department of Epidemiology and Preventive Medicine as well as other departments/programs at the University of Maryland, Baltimore (Physiology, Obstetrics and Gynecology, and Toxicology) are working on collaborative projects to identify risk factors for abnormal ovarian functions, early menopause, and late menopause. Among the major epidemiological studies are the Study on Risk Factors for Early Menopause (Dr. Flaws), the Study of Factors that Affect Ovarian Volume and Follicle Numbers in Women (Dr. Flaws and Dr. Patricia Langenberg), and the Study of Menopausal Hot Flashes in Mid-Life Women (Dr. Flaws and Dr. Langenberg). In addition, data from the Postmenopausal Estrogen and Progestin Intervention Trial (PEPI) study on the long-term follow-up effects of various estrogen/progestin regimens of the Hormone Replacement Therapy (HRT) on a variety of cardiovascular endpoints and coronary artery disease risk factors are available for analytic purposes (Drs. Flaws and Langenberg). Faculty in the Department of Epidemiology and Preventive Medicine (Drs. Flaws and Langenberg) have also acquired the data base from the Lipid Research Clinics (LRC) follow-up study and are involved in analyses that address the long-term risk of cardiovascular disease with HRT use. Drs. Flaws, Langenberg and Dr. Katherine Tkaczuk are conducting studies to examine why black and white postmenopausal women respond differently to HRT, breast cancer drugs such as tamoxifen, and other hormones.

Adverse Conditions and Diseases in Women

UMB has significant research efforts on cancer in women, not only on etiology and treatment but also on cancer disparities and community-based prevention. The University of Maryland Greenebaum Cancer Center has a new program in Cancer Disparities and Intervention Research designed to reduce the cancer burden of specific populations in Maryland by addressing cancer-related behaviors and the psychosocial, behavioral, and biological factors that influence cancer outcomes. This program translates findings from UMB's epidemiological and basic science studies into community-based intervention, clinical, and health services research. Cross-disciplinary research collaborations among the behavioral scientists, laboratory scientists, and epidemiologists at the UM School of Medicine are at the core of the Cancer Disparities and Intervention Research Program. The long-term goal of this program will be accomplished through research, education, and outreach initiatives with community-dwelling populations over the next five years. Community-based participatory research studies go beyond the individual risk factor approach to cancer prevention and control research. A social ecological framework guides investigations into the sociocultural context in which individual and population cancer risk occurs. This approach forms the conceptual basis for generating projects with community and health care organizations that serve large minority populations in the state of Maryland, and will be implemented through the Cancer Disparities and Intervention Research Program, directed by Dr. Claudia Baquet and co-directed by Dr. Sandra Brooks. Dr. Baquet's program of research includes The Maryland Special Populations Cancer Research Network (MSPN) funded by the National Cancer Institute (NCI-1U01-CA86249). This initiative supports the development, implementation and evaluation of a sustainable and robust infrastucture (the "Network") to promote cancer awareness and support cancer control activities in minority and medically-underserved communities in Maryland.

Under the leadership of Dr. Renee Royak-Schaler, behavioral science is being intergrated into the Cancer Disparities and Intervention Research Program at UMB. Training will be available to MORE-WH scholars in public health approaches to cancer control research, and multi-disciplinary models, which address the behavioral, sociocultural, and biological factors that determine cancer outcomes. Scholars will be encouraged to develop community-based projects using the principles of community-based participatory research. Dr. Royak-Schaler and colleagues in the PARTNERS in Breast Cancer Education Program (NCI-R01-CA-68336, 1996-2000), developed a model for implementing community-based participatory research with lay health advisors in African American churches. This model used both qualitative and quantitative research methodology to incorporate the cultural beliefs and practices relevant to this community to promote breast cancer early detection, prompt symptom care, and effective communication with primary care providers.

Within the laboratory of Dr. Angela Brodie's long-term interests in estrogen biosynthesis and its regulation in the ovary are directed toward understanding the importance of estrogen in breast cancer, employing immunocytochemistry, in situ hybridization, reverse transcription-polymerase chain reaction and flow cytometry to determine expression of aromatase in the normal breast and breast cancer, and the role of aromatase and angiogenesis in the processes of tumor growth and development. This laboratory has recently developed a new animal model using stably transfected cDNA to express aromatase in breast cancer cells. This model is proving valuable to determine mechanisms of the effects of estrogens, aromatase inhibitors and other hormone antagonists on the molecular events involved in the growth of breast cancer and endometrial tissue. The laboratory of Dr. Amy Fulton is focusing on expression of Cyclooxygenase (COX) enzyme in solid tumors, including breast cancers. She is particularly interested in examining how a high level of COX expression is induced in tumors, how COX inhibitors appear to inhibit growth and metastisis of malignant breast tumors, and how COX inhibitors modulate antitumor immune effector function. Dr. Antonino Passaniti and his laboratory are interested in transcription factor Runx2 in endothelial cell interactions with the extracellular matrix and in angiogenesis. Since this factor has been shown to regulate protease expression in breast cancer cells, he is examining its effect on breast tumor cell invasion, essential to tumor metastisis. Dr. Ginette Serrero is concerned with developing new treatments for estrogen receptor-negative breast cancer, which is normally not responsive to tamoxifen (TAM). Her research is also relevant for patients with cancers that initially responded to TAM, but that recur as resistant requiring additional systemic therapies. The identification of novel molecular targets for combined diagnosis and therapy of TAM-resistant breast cancer is the focus of her laboratory's research. Using their disease-based cell culture target discovery approach, they have purified and cloned a novel autocrine tumorigenic growth factor PCDGF. Her biological and clinical studies have provided a strong target validation for PCDGF to warrant the establishment of an innovative program of molecularly focused drug discovery. Dr. Katherine Tkaczuk, a full-time clinical faculty member at the Greenebaum Cancer Center, oversees a number of Phase I, II, and III clinical trials in patients with breast cancer and other solid tumor malignancies. Her research primarily focuses on the development of new therapies for early and advanced stage breast cancer.

Basic science studies in associations between neurological disease and ovarian hormones are a strong area of research at UMB. It is apparent that ovarian hormone status alters responses to a host of diseases that extend well beyond those directly involving the reproductive system. Among these, neurological diseases have received widespread attention following reports that women on hormone replacement therapy have a lower incidence of Alzheimer’s disease than untreated post-menopausal women, and that ovarian status affects the severity of brain damage from stroke. Moreover, a number of women with complex partial seizure disorders show marked fluctuation in seizure patterns with their menstrual cycle. These investigations have prompted active research into the potential neuroprotective role of ovarian steroids. Organized interactive interdisciplinary basic research conducted across the departments of Anesthesiology, Anatomy and Neurobiology, Neurology, and Pediatrics focuses on the role of ovarian hormones in brain injury following status epilepticus (Dr. Gary Fiskum, Dr. Gloria Hoffman), and in an animal model of multiple sclerosis (Dr. C. Lee Koski and Dr. Gloria Hoffman). These studies use state of the art approaches in cellular and molecular biology of mitochondrial function, cell signaling cascades, quantitative non-radioactive in situ hybridization, immunocytochemistry, anatomical signs of apoptosis in neurons, computer image analysis, and behavioral assessment of neuronal function. Dr. James Koenig is conducting studies examining how hormones and stress influence the brain, with possible consequences for conditions such as depression and anxiety. Dr. Robert Schwarcz's laboratory is concerned with mechanisms underlying nerve cell death in the central nervous system, with focus on the potential role of excitotoxic mechanisms in Huntington's disease, temporal lobe epilepsy, and schizophrenia. These studies include assessment of gender differences and effects of sex hormones.

Although a number of significant gender differences have been identified in Parkinson's disease (PD), there has been little focus on women's health issues in PD. PD is less common in women than men, suggesting that estrogen may have neuroprotective properties. Gender differences in levodopa therapy have been identified including differences in levodopa dosage and the frequency of levodopa-related complications. Estrogen is recognized to have multiple effects on dopaminergic function and significant interactions with levodopa metabolism and pharmacokinetics. Estrogen’s diverse effects on cognitive function, mood, urinary and sexual function may also play a role in Parkinson’s-related disability. As a member of the Parkinson’s Study Group, Dr. Lisa Shulman is Principal Investigator of a multicenter pilot clinical trial to evaluate the effects of estrogen replacement therapy in postmenopausal women with Parkinson’s disease.

Dr. Susan Keay works with Dr. Toby Chai (urologist) to try to understand the etiology of Interstitial Cystitis (IC), a chronic bladder disorder experienced primarily by women (90% of diagnoses). No bacterial or viral agent has been identified in connection with IC; symptoms include significant pain, and frequency and urgency of urination. Dr. Keay has discovered an antiproliferative factor (APF) that inhibits the proliferation of bladder epithelial cells in vitro, and regulates the production of epithelial cell growth factors.

Significant research is on-going at UMB in conditions common in older women. Dr. Jay Magaziner's research is focused on the consequences of hip fracture, health and long-term care, and methods for studying older populations to identify ways of enhancing functioning and improving the quality of life of older persons. Recently this work has expanded to examine interventions for improving post-fracture bone, muscle and functional status and to chart the sequelae of hip fracture.

Dr. Sandra Black focuses on the health and functional status of older diverse populations, and has recently been funded by NIH for a study of the relationship between diabetes, functional diability, and depression in the elderly Mexican-American popluation.

Dr. Denise Korniewicz in the School of Nursing is particularly interested in infectious disease and infection control, particularly related to patient and health care worker safety. She has conducted or supervised studies of risk factors for nosocomial infections in trauma patients, older adults, and children. She plans further investigation into the risk factors associated with emerging and re-emerging infections among women.

Gender Differences in Pain

It is well established that women exhibit a higher prevalence of specific pain syndromes, including temporomandibular disorders, neuropathic pain, fibromyalgia, migraine headaches and some forms of arthritis. Furthermore, variations in hormonal levels associated with the menstrual cycle, menopause, pregnancy and lactation have been shown to influence pain levels. Numerous research laboratories within the University of Maryland School of Medicine and the School of Dentistry are examining the central and peripheral neural mechanisms underlying sex differences in pain perception and the potential influence of gonadal steroids. Clinical studies utilizing functional magnetic resonance imaging are also underway (Dr. Joel Greenspan). Recently, the Dept. of Oral and Craniofacial Biological Sciences was awarded a program project grant to study how the body’s response to noxious stimuli is shaped by previous experience with pain. This is the largest grant ever received by the University of Maryland School of Dentistry. Ongoing integrative and collaborative studies between the School of Medicine and the School of Dentistry are focusing on the sex differences in visceral pain and the influence of gonadal steroids (Dr. Richard Traub), estrogenic influences on nociceptor excitability (Dr. Michael Gold), the influence of progesterone on nociceptive thresholds (Dr. Ron Dubner, Dr. Gloria Hoffman, and Dr. Ke Ren), and the neural mechanisms underlying sex differences in opioid analgesia. These studies are funded primarily by extramural grants from the NIH. Other investigators within this theme area are conducting research in trauma, injury and painful disorders. Dr. Gary Fiskum heads a campus-wide program in neuroinjury with focus on molecular mechanisms of neural cell death associated with acute neurodegenerative diseases. He has developed neuroprotective interventions based on these mechanisms of injury. Dr. Alison Trinkoff has been studying risk factors for substance abuse in nurses, including abuse of substances taken to ameliorate pain. She also conducts research on associations between workplace conditions for nurses and painful musculoskeletal disorders with a focus on the organization of the workplace. Dr. Mona Baumgarten has several large research studies underway on risk factors for pressure ulcers in elderly hospital and nursing home patients, primarily women. Pressure ulcers represent a common adverse outcome in this population and have a significant impact in terms of patient suffering.

Scholar Eligibility and Qualifications

Eligible candidates must

have a clinical doctoral degree (M.D., D.O., D.D.S., Pharm.D., Physical Therapy or Nursing) or a Ph.D. or its equivalent;
have completed any postgraduate training normally expected for a faculty appointment in their field (including clinical or postdoctoral fellowship training, or residency if they have chosen not to subspecialize);
not be or have been a Principal Investigator on an R01, R29 or subproject of a Program Project (P01), Center (P50, P60, U54) grant, mentored career development (K-series) grant, or other equivalent research grant awards;
not have more than six years of research training experience beyond their last doctoral degree; and
be a U.S. citizen or have been lawfully admitted for permanent residence and possess an Alien Registration Receipt Card (I-151 or I-155) or some other verification of legal admission as a permanent citizen.

MORE-WH Scholar Qualifications

Successful scholars will have
demonstrated excellence in scholarship as evidenced from their academic records and letters of reference;
a career commitment to research in women’s health;
well-defined professional goals and the potential to meet those goals;
research interests and a proposed project that fits into one or more of the research theme areas selected for this program:
- Life Changes in Women’s Health
- Adverse Conditions and Diseases in Women
- Gender Differences in Pain
recommendations from three current or past mentors.

Potential candidates should send a letter confirming eligibility for this program, desired start date (January 1 or July 1, 2002-2005) along with a current CV, a statement of professional goals and research interests in one of the program research theme areas and why you are a good candidate for the MORE-WH Program, and contact information for three (3) references (former or current mentors) t

Istvan Merchenthaler, M.D., Ph.D., D.Sc.
Program Director
Department of Epidemiology & Preventive Medicine
Room 9-00F, 685 W. Baltimore Street
Baltimore, Maryland, 21201
(410) 706-1350
imerchen@epi.umaryland.edu