Women's Reproductive Health Research
Career Development Center of Excellence

In 1998, the Department at UTMB was one of the first of a group of 12 departments of Obstetrics and Gynecology to receive funding for a Women’s Reproductive Health Research (WRHR) Career Development Center from the National Institute of Child Health and Human Development Office of Research on Women’s Health.

In 2004, the NIH recognized the achievements of the UTMB WRHR Center by awarding continued funding through 2009.

WRHR Center Objective

Our key goal has been to expand our existing infrastructure to develop Ob/Gyn physician scientists capable of competing at the cutting edge of research relevant to women’s reproductive health. The program provides training in the laboratory of established, NIH-supported Mentors in both clinical and basic science research. We have maintained an excellent group of experienced Mentors, both from within the Department and from other departments, who collaborate with our faculty and train fellows and/or junior faculty developing research careers. Success of the program is measured by the ability of Scholars to become independent researchers, as measured by their ability to acquire NIH funding and to direct future research in women’s reproductive health. Our first group of Scholars is already beginning to serve as valuable role models for fellows and junior clinical faculty.

Through our people and resources, experience, and commitment to excellence, the Department of Obstetrics & Gynecology is maintaining a first-class WRHR Center of Excellence at the University of Texas Medical Branch.

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WRHR Administration

Principal Investigator
Gary D.V. Hankins, MD
Professor and Chairman, Department of Obstetrics & Gynecology
Jennie Sealy Smith Distinguished Chair in Obstetrics & Gynecology
ghankins@utmb.edu

Program Director
Chandrasekhar Yallampalli, DVM, PhD
Distinguished Professor, Department of Obstetrics & Gynecology
Professor, Department of Neuroscience & Cell Biology
chyallam@utmb.edu

Administrative Coordinator
Cheryl R. Welch
crwelch@utmb.edu

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WRHR Mentors

GARLAND D. ANDERSON, MD
DEAN, SCHOOL OF MEDICINE
THOMAS N. AND GLEAVES T. JAMES DISTINGUISHED CHAIR
PROFESSOR, DEPARTMENT OF OBSTETRICS & GYNECOLOGY
ganderso@utmb.edu

RESEARCH ACCOMPLISHMENTS
Dr. Anderson’s research interests have been in the area of the hypertensive disorders of pregnancy and prematurity. He is author or co-author of 102 articles in peer-reviewed journals. He served as president of the Society of Perinatal Obstetricians in 1992. He also served as chairman of UTMB’s practice plan (1990–1994) that had the responsibility of managing the university’s ambulatory care clinic and Physicians’ Central Billing system. He has participated in an NIH multicenter study examining the effect of antenatal glucocorticoid to the mother and the incidence of respiratory distress syndrome in the newborn. In addition, he was PI on an NIH project examining the route of delivery and the frequency of intraventricular hemorrhage in the newborn. This study required obtaining a head ultrasound of the infant within the first hour of life. This study demonstrated that cesarean section did not reduce the frequency of intraventricular hemorrhage but did delay the timing of intraventricular hemorrhage. Dr. Anderson has focused recently on the adult consequences of fetal disease. Additionally, he is interested in research to reduce the racial disparities in pregnancy outcome. His attention over the past several years has been to develop a strong research infrastructure in the department to allow continued growth of basic and clinical research. In May 2003, Dr. Anderson was appointed Chair of the Steering Committee of the NICHD Maternal-Fetal Units Network.

FUTURE RESEARCH INTERESTS
Dr. Anderson has focused his attention most recently on insulin resistance in pregnancy and the fetal origin of adult diseases.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
All areas of research by Dr. Anderson relate to issues directly relevant to pregnant women and/or their fetuses.

DEMONSTRATED RECORD OF MENTORING
Dr. Anderson has trained 19 fellows in Maternal-Fetal Medicine. Among these fellows are Baha M. Sibai, MD, Professor and Chair, Department of Ob/Gyn at the University of Cincinnati School of Medicine; Joseph A. Spinnato II, MD, Professor and Vice Chair, University of Cincinnati School of Medicine; Antonio Gonzalez-Ruiz, MD, Director of Maternal-Fetal Medicine at The Toledo Hospital; John V. Dacus, MD, Clerkship Director, Director of Maternal-Fetal Medicine, Clinical Professor at Columbia South Carolina; and Erol Amon, MD, JD, Professor, Department of Obstetrics, Gynecology, and Women’s Health, Division of Maternal-Fetal Medicine at St. Louis University.

Dr. Anderson played an active role in designing all of the fellowships at the Department of Obstetrics & Gynecology at UTMB. He mentors the fellows’ progress and approves which mentors’ laboratories they spend their research time. Dr. Anderson’s mentorship of Dr. Monica Longo has resulted in a proposal entitled, “Circulating insulin levels as a predictor of glucose intolerance in later life.” The purpose of this study is to find out if a group of women in pregnancy (other than those with gestational diabetes) can be identified that are at risk for type 2 diabetes in later life. Dr. Anderson also is involved in basic research involving the fetal origins of adult disease.
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MAHMOUD S. AHMED, PHD
PROFESSOR, DEPARTMENT OF OBSTETRICS & GYNECOLOGY
GRADUATE FACULTY, DEPARTMENT OF PHARMACOLOGY & TOXICOLOGY AND HUMAN BIOLOGICAL CHEMISTRY & GENETICS
maahmed@utmb.edu

RESEARCH ACCOMPLISHMENTS
Pregnancy is associated with physiological changes that include the pharmacokinetics of administered medications. Human placenta plays a crucial role in regulating fetal growth and development as well as its protection from xenobiotics and administered medications. Investigations in our laboratory focus on understanding the mechanisms underlying the disposition of therapeutic agents used for treatment of the opiate addict and hypoglycemic drugs used for treatment of gestational diabetes. In addition, we are collaborating with other investigators on developing new drugs for treatment of nicotine addiction during pregnancy.

Dr. Ahmed’s laboratory, over the last two decades, has provided information on the molecular mechanism(s) leading to the development of tolerance to opiates utilizing human placenta as a model system. His laboratory identified the role of opiate receptors in human placenta, a noninnervated tissue, their endogenous ligand (dynorphin 1-8) and mediated responses (regulation of hCG and acetylcholine release) and demonstrated that the in vitro and or in vivo exposure of human placenta to opiates leads to the development of tolerance. His laboratory also identified a cocaine binding protein in human placenta and conducted a clinical investigation of cocaine use during pregnancy and its effects on maternal and neonatal outcome. Recently, his laboratory identified the role of human placenta as a functional barrier protecting the fetus from exposure to therapeutic agents by its disposition of the drugs.

Dr. Ahmed was recruited to UTMB in February 2002. He has received community awards for his research in drug abuse during pregnancy from the Kansas City Juvenile court and the March of Dimes and Birth Defects Foundation, and he was featured in numerous local newspaper articles and media interviews. He serves on the advisory board for “Team for Infants Endangered by substance Abuse” (TIES), a consortium of health and social care providers funded by the Federal and State of Missouri Governments. He also serves on committees for the March of Dimes Foundation. Research in his laboratory has been supported by the National Science Foundation, National Institute on Drug Abuse, National Institute of Child Health and Human Development, private organizations, and pharmaceutical companies.

FUTURE RESEARCH INTERESTS
Dr. Ahmed’s future research interests include translational and clinical investigations of therapeutics used for treatment of the pregnant patient. Specifically:

• Maternal-fetal pharmacology
• Disposition (pharmacokinetics) of therapeutics by human placenta
• Development of medications for treatment of the pregnant opiate addict and gestational diabetes
• The molecular mechanisms underlying the development of tolerance to opiates during pregnancy

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
Recently, NICHD selected the UTMB Department of Obstetrics & Gynecology as one of four sites in the United States for the Obstetrics Pharmacology Research Units (OPRU) to conduct translational and clinical investigations of therapeutics used for treatment of the pregnant patient. Dr. Gary D.V. Hankins is PI (Obstetrics) and Dr. Ahmed is Co-investigator (Pharmacology) of the UTMB site.

DEMONSTRATED RECORD OF MENTORING
Dr. Ahmed has mentored several junior faculty in the fields of pharmacology and obstetrics and gynecology, as well as 17 medical students; 3 pharmacy students; 16 graduate students in biochemistry, pharmacology and pharmaceutical sciences; and 9 postdoctoral fellows. Several of the students and post doctoral fellows have received regional and national awards for their presentations in national and international conferences. In 2001, the Doctoral Student Association at UMKC awarded Dr. Ahmed the “Outstanding Interdisciplinary Faculty Award” for “Outstanding Guidance, Inspiration, and Encouragement of Interdisciplinary PhD students.”
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ABBEY B. BERENSON, MD
(DIRECTOR, CLINICAL STUDIES CORE)
PROFESSOR, DEPARTMENT OF OBSTETRICS & GYNECOLOGY AND PEDIATRICS
CHIEF, DIVISION OF PEDIATRIC & ADOLESCENT GYNECOLOGY
DIRECTOR, DIVISION OF FAMILY PLANNING
DIRECTOR, CENTER FOR INTERDISCIPLINARY RESEARCH IN WOMEN’S HEALTH
abberens@utmb.edu

RESEARCH ACCOMPLISHMENTS
Dr. Berenson has developed an international reputation for the quality of her clinical studies of female children, adolescents, and young adults. The first area in which she developed expertise was the morphology of the hymen in prepubertal girls. When she entered academic medicine in 1989, little was known about the development of the hymen and how its appearance changed as a result of sexual abuse. This topic became clinically important because of increases in the request for genital examinations to determine if sexual abuse had occurred. Dr. Berenson designed and conducted both cross-sectional and longitudinal studies to address this issue. The results of these landmark studies have been published in top-tier journals for ob/gyn and pediatric specialists, and are frequently cited in the sexual abuse literature as the standard in the field.

Concurrent with the research program on hymenal anatomy, Dr. Berenson conducted large-scale clinical studies on hormonal contraception among adolescents and young adults. She has published 23 papers in this area, a number of which have appeared in prestigious journals. These studies have used a variety of study designs, from cross-sectional surveys to longitudinal clinical trials. In 2000, she was awarded an R01 grant from NICHD to investigate the effects of 20 µg birth control pills and DMPA on bone mineral density in women 16–33 years of age. Over 700 women have been recruited for this longitudinal study. Subjects will be followed for 2 years. Dr. Berenson has also published in the areas of domestic violence, substance use, and mood disorders.

FUTURE RESEARCH INTERESTS
Dr. Berenson’s future research will expand upon the multifactorial data being gathered in the current study of hormonal contraceptive effect on bone mineral density. The additional data on health behaviors, social issues, and mental health status in reproductive-aged women will also generate much needed information for development of culturally competent practices of gynecological care among underserved women. Dr. Berenson will expand research training opportunities for minority researchers by writing minority supplement applications for her ongoing contraceptive studies.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
As both a Mentor and Clinical Core Director, Dr. Berenson brings to the WRHR Career Development Center multiple possibilities for training obstetrician/gynecologists in patient-oriented research. WRHR trainees are assured a broad experience because of her extended internal activity at the divisional, departmental, and institutional levels, as well as external activity within regional sites.

As an Ob/Gyn faculty researcher, Dr. Berenson’s work on contraception and the hymen have contributed new information to traditional domains of pediatricians and gynecologists. Her interest in a broader range of women’s health issues, including family violence, substance use, dietary intake, and mental health, will continue to contribute to the needs of ob/gyns who are also providing primary care to a majority of women, especially those who are poor.

As Medical Director of the UTMB-affiliated Regional Maternal & Child Health clinics in southeast Texas, Dr. Berenson enjoys an ongoing collaborative relationship with Clinic Director Carolyn Nelson-Becker and her staff. The more than 30 Title X clinics serve African American, Hispanic, Asian, and white women with low incomes. The sites are also economically diverse, some with an industrial metropolitan base, while others are more rural or suburban in nature. This mix provides an ideal venue for investigation of lifestyle and contraceptive practices among underserved women. These clinics also contribute to the development of culturally competent researchers in reproductive health.

As Director of UTMB’s Center for Interdisciplinary Research in Women’s Health, Dr. Berenson anticipates a continuing reciprocal and synergestic relationship with the WRHR Career Development Center and its trainees. Both Centers share a number of faculty Mentors, as well as resources and training components. The direct connection between the two Centers affords WRHR trainees potential interaction with women’s health researchers from several disciplines.

DEMONSTRATED RECORD OF MENTORING
Dr. Berenson has mentored medical students, residents, and junior faculty throughout her academic career. She has coauthored 40 papers with previous mentees. All of the junior faculty that she has mentored have gone on to secure their own funding, and the medical students have received numerous awards and recognition. The NIH recognized her status as an established mentor in 2003, when she was awarded 5 years of funding under a K24, a career development mechanism that allows her protected time to focus on training young investigators in patient-oriented research.
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ROBERT E. GARFIELD, PHD
DIRECTOR, REPRODUCTIVE SCIENCES
PROFESSOR, DEPARTMENTS OF OBSTETRICS & GYNECOLOGY AND PHYSIOLOGY & BIOPHYSICS
rgarfiel@utmb.edu

RESEARCH ACCOMPLISHMENTS
Dr. Garfield has been involved in studies in reproduction for about 30 years. He has been a major contributor to the understanding of uterine and cervical physiology. His research studies focus on the regulation of uterine contractility and extend from the cellular level to whole animals and include examination of the hormonal, neural, and immunological systems, which control the contractile state of the uterine muscle, the myometrium. Dr. Garfield has published over 400 peer-reviewed papers or reviews and has an international reputation as an authority on uterine contractility, cervical ripening, and the events that maintain pregnancy and initiate labor. He is particularly interested in the factors that govern contractility during pregnancy. The major areas of his research pursuits deal with why the uterus remains quiescent during most of the pregnancy and how conversion to an active and reactive condition occurs at term. Studies in Dr. Garfield’s laboratory have shown that the small muscle cells of the uterus become electrically and metabolically coupled during labor and delivery. These observations account for the ability of the uterus to contract rhythmically and synchronously during labor. Further, his studies indicate that the steroid hormones control this step to initiate labor. In addition, he has done work on the role of steroids and nitric oxide synthases in the maintenance of pregnancy and the process of implantation. Recently, he has also shown that a nitric oxide-cGMP-relaxation system exists in the uterus and that it inhibits uterine contractility during pregnancy, but not during labor. Dr. Garfield has developed instruments for objective evaluation of the uterus and cervix based on recordings of uterine electromyographical (EMG) activity from the abdominal surface and measurements of cervical collagen with optical methods, respectively. Using these instruments, Dr. Garfield’s group has recently shown that true labor in women can be predicted with high confidence.

Dr. Garfield was one of the first to recognize that the myometrium passes through a conditioning phase in preparation for labor. The conditioning phase includes essential changes in the myometrial properties that allow for better electrical coupling, thereby facilitating forceful contractions. An understanding of the conditioning phase has led to a better perception of the process of labor. His most recent accomplishments include the role of nitric oxide in regulation of the myometrium and cervical connective tissue. His group has also recently shown that preterm labor may be associated with an allergic response.

FUTURE RESEARCH INTERESTS
Future studies will focus on normal and abnormal function of the female reproductive tract. Particular interest is placed on the events that control the uterus and cervix during pregnancy. In addition, a major effort of the studies is being directed at the cardiovascular function and adaptations during pregnancy. Dr. Garfield’s aim is to develop treatments to either stimulate or inhibit the uterus or cervix during pregnancy and to develop devices to measure the changes that occur and detect potential problems.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
The objectives are to define control systems that regulate the uterus and cervix during pregnancy and to develop diagnostic methods and treatments to prevent or initiate labor. Particular attention is directed towards an understanding of preterm labor, including its detection and treatment.

DEMONSTRATED RECORD OF MENTORING
During his career, Dr. Garfield has mentored over 50 students, fellows, and junior faculty. Many of these former trainees now occupy academic positions throughout the world.
Current members of the laboratory include William Maner, BA, BS; Stephen Marx, BS (graduate student); Ancizar Betancourt, MSc; Shao-Qing Shi, MD; Egle Bytautiene, MD; Lyn Mackay, BSc; and Yuri Vedernikov, MD, PhD.
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GARY D. V. HANKINS, MD
PROFESSOR AND CHAIRMAN, DEPARTMENT OF OBSTETRICS & GYNECOLOGY
JENNIE SEALY SMITH DISTINGUISHED CHAIR IN OBSTETRICS & GYNECOLOGY
CHIEF, DIVISION OF MATERNAL-FETAL MEDICINE
ghankins@utmb.edu

RESEARCH ACCOMPLISHMENTS
Dr. Hankins is a highly productive clinical scientist with over 140 refereed articles published. His most notable scientific contributions are in two primary areas. The first is clinical outcome studies. Dr. Hankins and his colleagues were pioneers regarding establishment of normative data for umbilical cord arterial and venous blood gas and acid base values and their meaning. They have further significantly contributed to our understanding of the correlation of the metabolic condition of the fetus to the electronic fetal heart rate patterns. This work led to his appointment as Chairman of the American College of Obstetricians and Gynecologists Task Force on Neonatal Encephalopathy and Cerebral Palsy. The other area of notable clinical expertise of Dr. Hankins involves multiple facets of operative obstetrics, to include the sentinel series involving early repair of episiotomy dehiscence, emergency cerclage usage, and operative vaginal delivery. Another major strength is his work as an investigator in the area of large primate physiology studies. He has amassed substantial experience in a number of models to include the canine, Capra hircus, and Papio cyanocephalus. His expertise with the yellow baboon has resulted in his being named as an adjunct scientist at the Southwest Foundation for Biomedical Research, the largest primate center in North America. In canine and primate models, the pathophysiology of beta-sympathomimetic drug induced pulmonary edema was defined. The most comprehensive study of the acute effects of amniotic fluid embolism published to date is that of Hankins and his colleagues. Combined with a national registry of amniotic fluid embolism cases in humans and resulting reports, Hankins is one of two notable scientists investigating this lethal disease entity. He has additionally performed pharmacokinetic studies of AZT in the maternal-fetal primate model and evaluated contrast agents, again in the primate model, for their ability to further refine uteroplacental blood flow dynamics.

Dr. Hankins has achieved extramural funding for a number of projects. Having spent the bulk of his academic and professional career in the military, he achieved a number of successful grants for large primate studies from the Surgeon General’s office of the United States Air Force. He additionally received grants from pharmaceutical and device houses for large primate studies. Since coming to UTMB, Dr. Hankins has served as a site principal investigator on two multicenter NIH sponsored studies: 1) The FASTER Trial: First and Second Trimester Evaluation of Risk for Aneuploidy; and 2) Vaginal Ultrasound Cerclage Trial Consortium. The FASTER Trial has been completed, and The Vaginal Ultrasound Cerclage Trial Consortium is still ongoing. He also is a co-investigator on four R01 studies (with PIs including Drs. Ahmed, Dong, Nowicki, and Yallampalli).

Recently, NICHD selected the UTMB Department of Obstetrics & Gynecology as one of four sites in the United States for the Obstetrics Pharmacology Research Units (OPRU) to conduct translational and clinical investigations of therapeutics used for treatment of the pregnant patient. Dr. Gary D.V. Hankins is PI (Obstetrics) and Dr. Ahmed is Co-investigator (Pharmacology) of the UTMB site. Three subprojects have been decided on by the OPRU Steering Committee: “Basic Clinical Research” project, “Glyburide” project, and the “Pittsburgh Cocktail” primate model project.

The aims of the “Basic Clinical Research” project are to determine the role of human placenta in the disposition of a hypoglycemic drug during gestation in healthy and those with gestational diabetes mellitus. These investigations will include the kinetics for transplacental transfer of the drug, the transporters involved and identification of the placental enzyme(s) responsible for its metabolism. The investigations will include placentas obtained from different gestational ages as well as from diabetics.

The aim of the “Glyburide” project is to compare the medication Glyburide in pregnant women with diabetes versus recently diagnosed women with type-2 diabetes mellitus. The purposes of this study are to: 1) study how the diabetic medication Glyburide works, 2) evaluate its safety as a treatment for gestational diabetes, and 3) to find out the pharmacokinetics (what the body does to the drug) and pharmacodynamics (what the drug does to the body) during the third trimester of pregnancy compared with recently diagnosed women with type-2 diabetes.

The aim of the “Pittsburgh Cocktail” project is to test the baboon model as a surrogate for the human as regards induction of drug metabolizing enzymes and the effects of pregnancy upon changes in induction of these enzymes.

FUTURE RESEARCH INTERESTS
Dr. Hankins is involved in an established and ongoing clinical database of amniotic fluid embolism patients. He is also the director of our gestational tissue bank, with emphasis on clinical diagnosis of diabetes, hypertensive diseases, fetal growth abnormalities, prematurity, chorioamnionitis, multiple gestations, and intrauterine fetal clinics. Special emphasis for all of these diagnoses relates to the impact of maternal race and ethnicity. He is also involved in a prospectively maintained database of neonates with encephalopathy and evaluation of the antecedents of that encephalopathy.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
All areas of research by Dr. Hankins relate to issues directly relevant to pregnant women and/or their fetus. In many areas, initial information developed in primate models can then be tested in actual patients.

DEMONSTRATED RECORD OF MENTORING
The majority of individuals that Dr. Hankins has mentored are clinicians and clinical scientists. Among them are Dr. William Barth, who currently serves as the Chairman of the Department of Obstetrics & Gynecology at Wilford Hall United States Air Force Medical Center; Dr. Andrew Satin is Chief of Obstetrics at the Uniformed Services University of the Health Sciences and National Medical Center in Bethesda, Maryland; Dr. Jeff Bloss at Eli Lilly Pharmaceutical Company; Dr. Chris Zahn is Military Consultant to the Surgeon General for Obstetrics and Gynecology, Director of Clinical Clerkships, and Head of Continuing Medical Education in the Department of Obstetrics and Gynecology at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, Staff Physician in the Department of Obstetrics and Gynecology at Walter Reed Army Medical Center in Washington, DC, and National Naval Medical Center (combined Obstetrics/Gynecology program) in Bethesda, Maryland; and Dr. Michael Gordon, who is Chief of Obstetrics at Wilford Hall. During his tenure as the Chairman at Wilford Hall, Dr. Hankins served as the Residency Program Director and had primary responsibility for the graduation of some 28 residents. From this group of 28, over 40% went on to achieve training in board certified fellowships. The fellowship program that he established at UTMB is the first in the nation to levy a simultaneous requirement to achieve a master’s degree in medical sciences. Graduates are listed below for the last 5 years.
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MANUBAI NAGAMANI, MD
PROFESSOR, DEPARTMENT OF OBSTETRICS & GYNECOLOGY
VICE CHAIRMAN FOR ACADEMIC AFFAIRS
CHIEF, DIVISION OF REPRODUCTIVE ENDOCRINOLOGY & INFERTILITY
mnagaman@utmb.edu

RESEARCH ACCOMPLISHMENTS
Dr. Nagamani is pursing her research in three major areas. One of the areas of research of Dr. Nagamani and her colleagues is to investigate the role of insulin resistance and hyperinsulinemia in the pathogenesis of polycystic ovarian disease (PCOD) and hyperthecosis of the ovaries. Ovarian hyperthecosis is a variant of PCOD associated with severe virilization. Earlier studies of Dr. Nagamani showed that women with hyperthecosis have increased insulin levels, and insulin stimulates ovarian androgen production. Further studies showed that the ovarian stroma of the women with PCOD/hyperthecosis have increased expression of LH receptors compared to normal ovaries there by increasing the responsiveness of polycystic ovaries to LH. Her recent studies indicate increased expression of mRNA encoding steroidogenic enzyme P450 17? in ovarian hyperthecosis, implying possible dysregulation of this enzyme in hyperthecosis. She is currently investigating the effect of insulin on various steroidogenic enzymes in the ovary. Her studies in women with polycystic ovarian disease include pulse analysis of luteinizing hormone secretion and insulin clamp studies to investigate the effect of hyperinsulinemia on LH secretion in these women. Her recent studies investigate the role of adipokines in the pathogenesis of PCOD.

Her second area of research is in studies on insulin resistance in normal postmenopausal women and those with endometrial cancer. Obesity and unopposed estrogen therapy are two known risk factors for development of endometrial cancer. However, one third of women who developed endometrial cancer are not obese and have never been on estrogen replacement therapy. Dr. Nagamani’s research in this area over the last decade indicate that hyperinsulinemia is one of the risk factors for development of endometrial cancer. Her investigations show that insulin stimulates ovarian stroma to produce increased amounts of testosterone and androstenedione and increases the availability of prehormones for estrogen formation from peripheral conversion. Her studies also show insulin stimulates proliferation of endometrial cancer cells in vitro. These studies indicate that insulin could have a direct effect on the endometrium and may play a role in the growth and/or development of endometrial cancer. Dr. Nagamani has had continuing funding from NIH for 10 years for these studies. Her studies also will determine specific factors that lead to the development of insulin resistance in postmenopausal women. She is also investigating the effect of Selective Estrogen Receptor Modulators (SERMS) and various Estrogen/Progesterone preparations on insulin resistance in postmenopausal women by insulin clamp studies. These studies are funded by Grants from Eli Lilly and Wyeth.

Her third area of research is on the effects of phytoestrogens and soy proteins on secretion of pituitary hormones and ovarian steroids. Her studies are designed to investigate the possible mechanisms by which isoflavones and flavones in a soy diet could decrease the risk of breast cancer and possibly endometrial cancer. She is investigating the effect of isoflavones on endometrial cells in culture. In collaboration with Dr. Lu from the department of PMCH, she is also investigating the effect of soy diet and isoflavone-free soy diet on the ovarian steroids and breast density. These studies are funded by a grant from the Department of Defence and a grant from the American Institute for Cancer Research.

FUTURE RESEARCH INTERESTS
There are ongoing studies in all of the above mentioned areas. In ovarian hyperthecosis, studies are underway to evaluate the effect of insulin on the steroidogenic enzymes in the ovarian stroma. These studies involve Northern analysis for mRNA for steroidogenic enzymes P450scc, P450 17?, and P450 arom in the ovarian stroma from normal ovaries and in PCOD/ovarian hyperthecosis. Studies are also underway to investigate the nature of insulin resistance in postmenopausal women and the effect of age and duration of menopause on insulin resistance. She is also investigating possible estrogenic or antiestrogenic effects of isoflavones in postmenopausal women.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
The overall aim of Dr. Nagamani’s studies is to investigate the role of hyperinsulinemia in ovarian hyperandrogenism and its possible role in postmenopausal women on the growth and development of endometrial cancer. Other studies are on the effect of soy proteins and isoflavones on postmenopausal health. All these studies are very relevant to women’s health issues.

DEMONSTRATED RECORD OF MENTORING
Dr. Nagamani has mentored many clinician scientists who are currently in academic positions in various institutions. As chief of the Division of Reproductive Endocrinology, she has mentored all junior faculty in her division to establish their research careers. Several of the residents who were trained in basic research in her laboratory, have elected to do fellowships in Reproductive Endocrinology and have stayed in academic medicine. Faculty she is currently mentoring in her division include Dr. Chakrabarty, and Dr. Phelps.
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MELVYN S. SOLOFF, PHD
(DIRECTOR, MOLECULAR BIOLOGY CORE)
PROFESSOR, DEPARTMENT OF OBSTETRICS & GYNECOLOGY AND
SENIOR SCIENTIST, SEALY CENTER FOR MOLECULAR BIOLOGY
msoloff@utmb.edu

RESEARCH ACCOMPLISHMENTS
Dr. Soloff’s research interests deal primarily with signal pathways and regulation of gene expression in human uterine smooth muscle cells, as pertains to proliferation and contractile activity. In the latter case, the laboratory focuses on the mechanisms of spontaneous labor and the etiology of preterm labor, which is the single leading cause of infant mortality and morbidity. Recent studies have involved in situ chromatin immunoprecipitation analysis of promoter regulation for the oxytocin receptor, cyclooxygenase-2, and interleukin 8 genes. The laboratory has also been elucidating pathways between activation of oxytocin receptors and prostaglandin production, the actions of lysosphosphatidic acids, and the role of regulators of G protein signaling in human myometrial cells.

FUTURE RESEARCH INTERESTS
Future research will concentrate on continuation of the major ongoing projects in the laboratory and on the production of cytokines by human myometrial cells.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
The overall aims of the laboratory are to construct plausible models of events leading to the onset of spontaneous labor and parturition. Once these processes are understood, the question of what happens in preterm labor and abortion can be approached. It is clear that this research is extremely relevant to issues in obstetrics and gynecology.

DEMONSTRATED RECORD OF MENTORING
Dr. Soloff has served as a mentor for 1 PhD student, 11 postdoctoral fellows, and 2 fellows in Maternal-Fetal Medicine. Shilla Chakrabarty, PhD, is the recipient of a K01 grant with Dr. Soloff as her mentor.
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CHANDRASEKHAR YALLAMPALLI, DVM, PHD
(PROGRAM DIRECTOR, WRHR CENTER OF EXCELLENCE)
DISTINGUISHED PROFESSOR, DEPARTMENT OF OBSTETRICS & GYNECOLOGY
PROFESSOR, DEPARTMENT OF ANATOMY & NEUROSCIENCES
chyallam@utmb.edu

RESEARCH ACCOMPLISHMENTS
Dr. Yallampalli’s research interests have focused on three major areas: 1) the role of nitric oxide (NO), calcitonin gene-related peptide (CGRP), and adrenomedullin (AM) in uterine physiology and in bone mineral metabolism; 2) the role of CGRP and AM in vascular adaptations during pregnancy; and 3) the role of NO in the regulation of uteroplacental infection and fetal growth. His original studies demonstrating the role of the NO system in the uterus in maintaining uterine quiescence during pregnancy has stimulated major interests in this area. His laboratory, using various pharmacological, biochemical, and molecular biological methods and in vivo manipulations, demonstrated that NO is generated in the uterus and both NO generation and its effects on relaxation of the uterus are substantially increased during pregnancy and decreased at term. These studies by Dr. Yallampalli have provided fundamental understanding on the involvement of NO systems in the uterine quiescence during pregnancy. Subsequent in vivo studies by Dr. Yallampalli demonstrated that inhibition of NO synthesis, together with reduced progesterone action, leads to preterm labor and delivery and that NO donors can prevent preterm labor induced by prostaglandin F2? in rats. These studies provide a functional role for NO in maintaining uterine quiescence during pregnancy. In addition, Dr. Yallampalli’s studies have demonstrated that exogenously administered NO donors can reverse loss in bone density and that beneficial effects of estradiol on the bone appeared to be mediated through the NO system, providing a novel mechanism for estradiol action in this tissue.

Dr. Yallampalli’s studies are fundamental in developing an in vivo animal model for studies on preeclampsia in humans. Using this model, a variety of agents were screened for their effectiveness in reversing signs of preeclampsia. One of the peptides that Dr. Yallampalli tested was calcitonin gene-related peptide (CGRP). CGRP not only reversed the hypertension, but also the fetal effects in those animals in which hypertension was induced. These studies of Dr. Yallampalli demonstrate that CGRP plays a compensatory vasodilator role during pregnancy and that the vasodilator effects of CGRP are regulated by progesterone, providing a novel mechanism for blood pressure regulation by steroid hormones in the female. In addition, Dr. Yallampalli, in collaboration with Dr. Yuan-Lin Dong, has demonstrated that the umbilical and placental chorionic vessel vasorelaxation to CGRP is compromised in preeclamptic patients. Infusion of antagonists of CGRP or AM effectively reduced fetal growth in rats, indicating their role in fetal growth. Urogenital infections and associated perinatal complications including preterm labor and fetal growth restrictions are another area of investigation. Dr. Yallampalli, in collaboration with Dr. B. Nowicki, have found that NO regulates the severity of uterine infection leading to the fetoplacental growth alterations. NO appears to modulate the severity of infection by altering the receptors for the bacteria with specific virulence factors such as Dr.

FUTURE RESEARCH INTERESTS
Dr. Yallampalli’s future research will focus on the hormonal and pregnancy regulation of uterine CGRP and AM systems in the maintenance of uterine quiescence and initiation of labor. This effort will include molecular studies on the regulation of CGRP and AM receptor gene expression, as well as second messenger expressions in the uterus. In the studies on the role of CGRP and AM in regulating vascular functions in the female and during pregnancy, he will focus on the molecular mechanisms involved in the gene regulation and receptors for CGRP and AM in various vascular beds. In addition, these studies will also include measurements of systemic and regional hemodynamics and their regulation by steroid hormones and CGRP. Another exciting area of focus is to investigate the mechanisms responsible for fetal growth restriction and placental abnormalities in pregnant rats receiving antagonists of CGRP and AM. Theses include apoptotic changes and blood flow regulation. A fourth area of investigation includes the mechanisms through which NO plays a role as a host defense to restrict infection in the uterus.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
This laboratory has made significant contributions to our knowledge and understanding of the role of the NO system, CGRP, and adrenomedullin in uterine and vascular tissues in the female and during pregnancy. These studies continue to be funded by the NIH (1994–2007). Several MD and PhD postdoctoral and predoctoral fellows have been trained in this laboratory. With several ongoing innovative research projects, this laboratory offers an excellent opportunity for training young faculty interested in the regulation of uterine and vascular functions and the mechanisms of regulation by steroid hormones.

DEMONSTRATED RECORD OF MENTORING
Dr. Yallampalli has served as a mentor for 2 MS students, 3 PhD students, 10 postdoctoral fellows, 5 post-MD research fellows, and 2 WRHR Scholars—in addition to serving on supervisory committees of 8 PhD students. More than 15 undergraduate and high school students have received research training in his laboratory. Six of the trainees have moved up the ranks to faculty members at UTMB and other institutions and have successfully received extramural funding including one R01, several R03s, and one American Heart Association grant. Current members of the group include: Dr. Y.L. Dong, MD, PhD; Xiaoquan Zhang, PhD; M. Chauhan, PhD; Chandrasekhar Thota, PhD; Gracious Ross, PhD; and Katarzyna Wroblewska-Seniuk, MD. Dr. Yallampalli has been honored at the annual meetings of the Society for Gynecologic Investigation every year from 1996 to 2001 for mentoring fellows who received outstanding abstract awards by the Society. For his consistent funding record and successful mentoring abilities, he was honored with the “Distinguished Professorship in Obstetrics and Gynecology Research and Mentoring Excellence.”
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WLODZIMERZ M. BUJALOWSKI, PHD
PROFESSOR, DEPARTMENTS OF HUMAN BIOLOGICAL CHEMISTRY & GENETICS,
OBSTETRICS & GYNECOLOGY, SEALY CENTER FOR STRUCTURAL BIOLOGY, AND SEALY CENTER FOR CANCER CELL BIOLOGY
wbujalow@utmb.edu

RESEARCH ACCOMPLISHMENTS
The laboratory is currently carrying out two major projects both funded by independent R01 grants from NIH.

In the project focused on the helicase mechanism, Dr. Bujalowski has already established several fundamental aspects of interactions of the E. coli primary replicative helicase DnaB protein with DNA and nucleotide cofactors. He was the first to establish that the enzyme forms a stable ring-like hexamer structure specifically stabilized by magnesium cations and binds DNA in a strictly one-directional orientation. The data also provided the first evidence that a stable hexameric helicase binds ssDNA not through assembling around the nucleic acid, as commonly thought, but through local opening of the hexamer structure.

The second project focuses on the DNA recognition mechanism of a DNA repair polymerase, and it addresses the specific damaged-DNA recognition by mammalian polymerase beta and the role of the enzyme domains in its activities.

FUTURE RESEARCH INTERESTS
Future research interests will focus on elucidation of the hexameric helicase functioning in DNA replication, recombination, and repair on a molecular level. This can be accomplished through thermodynamic, dynamic, and structural studies of relevant protein nucleic acid interactions. These studies will involve both prokaryotes and eukaryote enzymes. Subsequently, studies will be extended to enzymes of different oligomeric structure including monomeric helicases. We will continue our research on fundamental aspects of damaged DNA recognition by mammalian DNA-repair polymerases.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
Dr. Bujalowski has been collaborating with Dr. Bogdan Nowicki, a member of the Department of Obstetrics & Gynecology and mentor in the Cell Biology and Physiology core, on structural aspects of decay accelerating factor. Although Dr. Bujalowski’s area of research is not presently associated with women’s health, he provides an area of expertise such that he may serve as a second Mentor to Scholars who find that their research interests lead to detailed structural studies in the course of their investigations.
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B. MARK EVERS, MD
PROFESSOR, DEPARTMENTS OF SURGERY AND HUMAN BIOLOGICAL CHEMISTRY & GENETICS
mevers@utmb.edu

RESEARCH ACCOMPLISHMENTS
Dr. Evers completed his surgical training at the University of Louisville in 1988 and then performed a Research Fellowship under the mentorship and guidance of Drs. Courtney M. Townsend and James C. Thompson from 1988 to 1990. He joined the faculty as an Assistant Professor and is currently the Professor and Robertson-Poth Distinguished Chair in General Surgery. In addition, he is the Director of the Surgical Research Laboratory, the Director of the Gastrointestinal Research Interdisciplinary Program (GRIP) at UTMB, and the Interim Director of the Sealy Center for Cancer Cell Biology. He is a member of the graduate school faculty. Dr. Evers has authored over 100 peer-reviewed publications, over 30 reviews and book chapters, and over 100 abstracts. Dr. Evers’ research has been continuously funded from the NIH for 10 years. He currently has an R37 (MERIT Award), an R01 award, a Training Grant from the National Institutes of Health, and he directs Project 1 and a Molecular Biology Core of a Program Project Grant (C.M. Townsend, MD, PI). Dr. Evers is the Associate Editor of two major textbooks; he is on the editorial board of six journals, and he serves as a regular member of the Surgery and Bioengineering Study Section for the NIH. He has played an integral role in the training of a number of young surgical scientists who are in academic positions of prestigious fellowships throughout the country. He has also served in leadership positions in national and international societies and is currently the immediate Past-President of the Society of University Surgeons, the most influential association of academic surgeons in North America.

FUTURE RESEARCH INTERESTS
Dr. Evers’ future research interests include mechanisms of intestinal differentiation and adaptation; molecular analysis and function of the neurotensin peptide; and mechanisms of pancreatitis.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
Dr. Evers has specific clinical and research interests in the regulation of growth differentiation and adaptation of normal gut tissues. A particular focus of his laboratory has been the molecular analysis of expression of the neurotensin gene in the gut. Dr. Evers is the Director of the Surgical Research Laboratory and James E. Thompson Molecular Biology Laboratory. All of the surgery trainees have utilized the facilities and expertise available in the Molecular Biology Laboratory to learn to perform and incorporate molecular techniques in their studies. His broad interests in cancer and cell signaling, and the excellent core facilities provided by the Department of Surgery, make him a very attractive mentor candidate for WRHR Scholars interested in cancer of the reproductive tract.

DEMONSTRATED RECORD OF MENTORING
Dr. Evers has specific clinical and research interests in the regulation of growth differentiation and adaptation of normal gut tissues. A particular focus of his laboratory has been the molecular analysis of expression of the neurotensin gene in the gut. Dr. Evers is the Director of the Surgical Research Laboratory and James E. Thompson Molecular Biology Laboratory. All of our trainees have utilized the facilities and expertise available in the Molecular Biology Laboratory to learn to perform and incorporate molecular techniques in their studies. In the last 10 years, Dr. Evers has served as research mentor to 12 trainees (10 Surgery Fellows, 1 Fellow in Gynecologic Oncology, and 1 MD/PhD student). Currently, Dr. Evers is serving as a research mentor for one Instructor in the Department of Surgery (Dr. Kim), three resident/fellows (Drs. Thomas, Farrow, Slogoff, and Held) and one MD/PhD student (Richard Ethridge). Dr. Barbara Held, a Fellow in Gynecologic Oncology, received training in molecular biology in his laboratory from 2001 to 2002.
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JEAN L. FREEMAN, PHD
ASSOCIATE PROFESSOR, DEPARTMENTS OF INTERNAL MEDICINE (GERIATRICS) AND PREVENTIVE MEDICINE & COMMUNITY HEALTH
jfreeman@utmb.edu

RESEARCH ACCOMPLISHMENTS
Dr. Freeman has designed and directed studies in health services for over 15 years. Her recent work has focused on the use of administrative datasets (Medicare data and tumor registry data) to assess the quality of breast cancer care nationally and the factors associated with quality care. Over the past 6 years, she has had funding from the Department of Defense and the National Cancer Institute to examine the use and outcomes of mammography services in older women.

Dr. Freeman is Director of the Health Care Delivery and Outcomes Research Program, which is jointly sponsored by the Department of Preventive Medicine & Community Health and the Sealy Center on Aging. She teaches courses in research methods (Outcomes Research, Methods in Health Services Research) and supervises dissertation research for doctoral students enrolled in our Clinical Science doctoral program. In addition, she is an Associate Director of the Clinical Research Education Office, Coordinator of the Health Services Research Curriculum in the Clinical Sciences Graduate Program, Co-Director of the Clinical Research Scholars Program, and a faculty member on the Health of Older Minorities training grant (National Institute on Aging).

FUTURE RESEARCH INTERESTS
Dr. Freeman is Director of the Health Care Delivery and Outcomes Research Program, which is jointly sponsored by the Department of Preventive Medicine & Community Health and the Sealy Center on Aging. She is developing the graduate curriculum in health services research and is also on the faculty of the Health of Older Minorities training grant (National Institute on Aging).

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
Since 1992, Dr. Freeman’s research has investigated factors related to the health and health care of older women. She has served as Principal Investigator or co-investigator on grants to examine the use and outcomes of breast cancer screening, diagnosis, and treatment services. This research utilizes a database created by the National Cancer Institute that contains tumor registry data from the SEER registries merged with Medicare claims data from the Health Care Financing Administration. Of interest is the effectiveness of screening mammography in older women, with a focus on the very old (75+) and disadvantaged populations. Also of interest is the extent to which older women are receiving appropriate care for breast cancer and how this affects health outcomes, such as breast cancer mortality and survival. A major aim of this research is to investigate whether the disparities in mortality and survival observed in older minority and economically disadvantaged populations can be explained by their lower use of screening and appropriate therapy.

DEMONSTRATED RECORD OF MENTORING
In her work with the Health of Older Minorities training grant and the Preventive Medicine & Community Health Graduate Program, Dr. Freeman has had extensive experience mentoring predoctoral and post doctoral students in health services research. In particular, she has supervised student research projects related to medication use, cancer screening, and the prevalence of arthritis in older Hispanic women as well as projects related to breast cancer care.

In September 2001, she was awarded a grant on Health Services Research in Underserved Populations by the Agency for Healthcare Research and Quality to strengthen UTMB’s capacity to conduct rigorous health services research. Through this grant, she and co-PI Gayle Weaver are building a faculty development program that includes advanced training in research methods and data analysis, short courses in scientific writing, and a mentoring system to support research proposal development for NIH grant submissions.
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MARK R. HELLMICH, PHD
ASSOCIATE PROFESSOR, DEPARTMENTS OF SURGERY AND PHYSIOLOGY AND BIOPHYSICS
mhellmic@utmb.edu

RESEARCH ACCOMPLISHMENTS
Our laboratory has made major contributions to understanding the role of peptide hormones and their cognate receptor in human cancer development and progression. Dr. Hellmich found a novel receptor splice variant that is expressed in human cancers and has characterized the molecular signal transduction pathways by which peptide hormones regulate tumor cell proliferation and angiogenesis. These studies continue to be funded by the NIH (2001–2006).

FUTURE RESEARCH INTERESTS
My future research will focus on defining the role of peptide hormones and their cognate receptors in carcinogenesis in the female reproductive tract.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
Several MD postdoctoral and predoctoral students have been trained in the laboratory. With several ongoing innovative research projects, this laboratory offers an excellent opportunity for training young faculty interested in defining the molecular mechanisms by which peptide hormones regulate carcinogenesis and angiogenesis. Dr. Hellmich is serving as mentor for two Gynecologic Oncology Fellows: Candice Nelson, MD (Bombesin stimulates pro-angiogenic gene expression in ES-2 ovarian cancer cells), and Lyuba Levine, MD (Gastrin releasing peptides and endometrial cancer).
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ALEX KUROSKY, PHD
PROFESSOR, DEPARTMENT OF HUMAN BIOLOGICAL CHEMISTRY AND GENETICS
FACULTY OF THE SCHOOL OF MEDICINE
FACULTY OF THE GRADUATE SCHOOL OF BIOMEDICAL SCIENCES
DIRECTOR, NATIONAL HEART, LUNG, AND BLOOD INSTITUTE PROTEOMICS CENTER
DIRECTOR, BIOMOLECULAR RESOURCE FACILITY
akurosky@utmb.edu

RESEARCH ACCOMPLISHMENTS
Alexander Kurosky, PhD has over 30 years experience in the areas of protein structure, function, and genetics. His experience includes significant technology development and implementation related to proteins. He is currently Director of the UTMB Biomolecular Resource Facility (BRF) and the NHLBI Proteomics Center. His major area of research focus has been proteolytic enzyme structure and function, proprotein processing enzymes, and proteomic technologies, especially related to airway inflammation. He is a Professor in the Department of Human Biological Chemistry and Genetics (~60 faculty), and was recently its Vice-Chairman for a 3-year rotating term. He is also an Associate Member of the UTMB Sealy Center for Structural Biology, a Member of the UTMB NIEHS Center in Environmental Toxicology and the Sealy Center for Environmental Health and Medicine, and was also the Associate Director for Basic Research and Shared Resources in UTMB’s NCI Cancer Center (1982–1987).

Dr. Kurosky received his Ph.D in biochemistry/protein chemistry from the University of Toronto, and his postdoctoral training in molecular genetics at UTMB. He has been the PI or a co-PI on over 20 NIH and NSF grants, and PI on five instrumentation grants. He has some 224 published articles and abstracts. He provides training, consulting, and collaborative interaction to faculty requiring expertise in protein chemistry on a regular basis. Internationally recognized, in the last 5 years he has conducted analyses of characterized proteins for investigators from some 76 institutions around the world. He has also worked with biotechnology companies (Applied Biosystems) in instrument development, and has ß-tested biotechnology equipment. In summary, Dr. Kurosky has a demonstrated track record of leading crossdisciplinary groups of researchers.

FUTURE RESEARCH INTERESTS
Dr. Kurosky’s present and future research interests will focus primarily on the development of proteomic technologies to study biological processes, especially airway inflammation and the eosinophil proteome. Other future research activities will include how peptide and protein hormones are synthesized, processed, packaged into secretory vesicles, and routed to target sites of action. Additional research interests focus on general aspects of protein structure, function, and genetics.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
The NHLBI Proteomics Center and the Biomolecular Resource Facility, under the direction of Dr. Kurosky, will provide trainees an excellent in-depth opportunity to gain knowledge relating to protein expression, genetics and structure function relationships. In particular, the Proteomics Center will provide trainees advanced technological capabilities to investigate biological processes in a global and discovery fashion, heretofore unattainable. Furthermore, the above facilities have trained staff whose expertise will additionally benefit trainees.

DEMONSTRATED RECORD OF MENTORING
Dr. Kurosky has guided 8 fellows through their postgraduate training in endocrinology.
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JOHN PAPACONSTANTINOU, PHD
PROFESSOR, DEPARTMENT OF HUMAN BIOLOGICAL CHEMISTRY & GENETICS
jpapacon@utmb.edu

RESEARCH ACCOMPLISHMENTS
The research program focuses upon two major areas dealing with the molecular biology and molecular genetics of aging and longevity. The laboratory’s approach to these projects is through the use of state-of-the-art molecular probes in combination with transgenic and knockout mouse models. A Program Project grant focuses upon the regulation of stress response genes and the signaling cascades that target these genes in eukaryotic tissues (liver, brain, and muscle). Dr. Papaconstantinou’s lab has shown that aging results in the development of a state of chronic inflammatory stress and that this occurs in the absence of an inflammatory challenge, such as bacterial lipopolysaccharide (LPS) and mitochondrial damaging agents that generate ROS, such as 3-nitropropionic acid. In addition, aging tissues exhibit a prolonged response to these inflammatory agents, suggesting that the ability to recover from an inflammatory challenge is age related. His goal is to understand the mechanism of these age-associated changes in gene regulation and signaling cascade activities that lead to the chronic inflammation and decreased ability to recover from inflammatory stress. Presently, his research focuses upon whether protein structural changes due to protein modifications (phosphorylation) in aged tissues affect protein-protein interactions and kinase activities, thereby altering the processes of signal transduction and the regulation of targeted stress response genes. A second program focuses upon understanding the molecular genetic basis of determination of longevity of the Snell dwarf and Ames dwarf mice. These mice have (a) mutations of either the Pit-1 or Prop-1 loci, respectively, that result in failure of development of somatotropes (GH), thyrotropes (TSH), and lactotropes (prolactin) of the anterior pituitary, and (b) live approximately 40–60% longer than normal. Dr. Papaconstantinou hypothesizes that the GH deficiency, which results in a nonfasted decrease of circulating insulin/IGF-1 levels, is a factor in the decreased function of the insulin/IGF-1 signaling pathway; (b) that these mutants exhibit characteristics similar to those caused by the weak mutation of daf-2, age-1, or daf-16 loci that result in the increased life span of the nematode, C. elegans; and (c) that attenuation of this pathway in the mouse mutants, as in the nematode, decreases oxidative stress and favors the development of resistance to oxidative stress, both of which correlate with longevity. His goal is to demonstrate that the molecular and genetic mechanisms of attenuation of the insulin/IGF-1 pathway in the mouse mutants are the basis for development of the molecular genetic program of longevity of these mice. In summary, the overall working hypothesis states that oxidative stress is a major factor in the development of age-associated biochemical phenotype and age-associated diseases, and that determination of longevity involves a complex genetic program activated during the early phases of maturation growth that slows down the development of aging biochemical characteristics.

FUTURE RESEARCH INTERESTS
The laboratory recently demonstrated that there is a significant increase in oxidatively damaged proteins in aged liver organelles, eg, mitochondria, endoplasmic reticulum, and peroxisomes. The mitochondrial proteins that are highly at risk for oxidative damage are components of the ET-Complexes I-V. They have shown that these proteins are all localized in the mitochondrial matrix and we propose that the oxidative damage elicits a mitochondrial unfolded protein stress response. The ER proteins are mainly chaperone proteins. These data suggest that aging may affect the chaperone activity required for proper protein folding. The overall goal is to determine whether age-associated increase in oxidative damage is a factor in the development of a state of chronic stress in aged tissues.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
Many of the clinical problems that WRHR investigators are studying are related to problems of age-associated diseases. We have the ability and resources to assist their investigators in developing molecular and cellular research programs that address these problems. Dr. Papaconstantinou has served as mentor for Dr. Concepcion Diaz-Arrastia, whose project involves a genomic and proteomic analysis of early cervical carcinoma.
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LAWRENCE R. STANBERRY, MD, PHD
PROFESSOR AND CHAIRMAN, DEPARTMENT OF PEDIATRICS
DIRECTOR, SEALY CENTER FOR VACCINE DEVELOPMENT
lrstanbe@utmb.edu

RESEARCH ACCOMPLISHMENTS
Dr. Stanberry’s research activities are focused on the pathogenesis of genital herpes, vaccine development, and topical microbicide evaluation. He is the co-principal investigator of a NIAID-funded Sexually Transmitted Diseases Research Center. The center, a consortium with Louisiana State University in New Orleans is one of six in the nation. The Louisiana branch will research STDs and other infections of the reproductive tract. This branch will focus on infections including Chlamydia and Trichomonas, as well as the bacterium Mycoplasma genitalium, found more in the Gulf South than in other states. The Galveston branch will focus on how enhancing innate immunity might help protect women against STDs. Dr. Stanberry was a principal investigator on the recent clinical trial of a vaccine for genital herpes that showed partial efficacy in HSV-1 seronegative women. This vaccine is being further evaluated in trials, and Dr. Stanberry is involved in studies assessing its safety and immunogenicity in girls 10 to 18 years of age.

FUTURE RESEARCH INTERESTS
Dr. Stanberry’s career has been devoted to addressing the significant public health problem of genital herpes. Genital herpes is a disease that has a greater impact on women due to a higher incidence and the devastating consequences of neonatal transmission. The recent finding of a gender-specific effect of a candidate genital herpes vaccine will provide important opportunities to investigate gender issues associated with immunological responses.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
Dr. Stanberry is currently the Director of the Sealy Center for Vaccine Development (SCVD). A key mission of the SCVD is to promote young investigators interested in vaccine development and acceptance. Dr. Stanberry has published over 100 peer-reviewed articles, reviews, and chapters, and he has written or edited three books. Many of his published works have been co-authored with students or mentored junior faculty. His interest in genital herpes fits very appropriately into the WRHR area of interest.

DEMONSTRATED RECORD OF MENTORING
Dr. Stanberry has been committed to the development of professionals in both clinical and basic science research fields. From 1982 to 2000, he was a faculty member at the Children’s Hospital Medical Center (CHMC). It is noteworthy that when Dr. Stanberry moved to UTMB to become the chairman of Pediatrics, he brought with him four scientists who he had actively mentored either as postdoctoral fellows or as junior faculty. Three of these faculty members have R01s, and the fourth is the project leader on a funded U01 program.
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DANIEL L. TRABER, PHD
PROFESSOR, DEPARTMENTS OF ANESTHESIOLOGY AND PHYSIOLOGY
CHIEF, DIVISION OF ANESTHESIA RESEARCH
dltraber@utmb.edu

RESEARCH ACCOMPLISHMENTS
Dr. Daniel L. Traber is the Charles Robert Allen Professor of Anesthesiology and a Professor of Physiology and Biophysics. Dr. Traber came to UTMB as a student in 1959, and, with the exception of a 1.5-year postdoctoral fellowship at Ohio State University in Columbus and a 1-year sabbatical in Vienna, he has been at UTMB ever since. In the department of Anesthesiology, he is the Director of a large core laboratory facility where intensive care research is accomplished. He regularly participates in both national and international courses in the area of critical care. In the School of Medicine, he has in the past been the Director of the Integrated Functional Student Laboratories and has taught in the Medical Physiology course. He has served on the Curriculum, Grading, and Promotions; Animal care; Appointment, Promotions, and Tenure; Academic Planning; and McLaughlin committees. He presently serves on the Animal Crisis Task Force and the Advisory Task Force for the Animal Resource Center. He is a long-time member of the scientific staff of the Shrine Hospital and is presently on its Executive Committee. Dr. Traber is a member of many Scientific Societies. He has been an officer of The American Burn Association, The Shock Society, The International Society for Burn Injuries, and The Society for Critical Care Medicine. He is a Cardiovascular Fellow of the American Physiological Society and a Fellow of Critical Care Medicine. Dr. Traber serves of the editorial board of the journals Critical Care Medicine, Shock, and The Journal of Burn Care and Rehabilitation. He has served study sections of the National Institutes of Health and The American Heart Association and was an ad hoc member of Council of the Institute of General Medical Sciences. He was formerly an associate of the National Board of Medical Examiners. Dr. Traber is the author of over 400 book chapters and scientific articles

FUTURE RESEARCH INTERESTS
Dr. Traber continues to be interested in research into the cardiopulmonary effects of trauma to the lungs, such as that seen with burns and smoke injuries. He currently is principle investigator on an NIH grant looking at the effects of selectins in lung injury and a program project grant to the NIH, along with four other investigators. This project examines the many aspects of lung injury and trying to ameriolate the consequences of trauma to the lungs. Dr. Traber has extensive funding from the Shriners of North American to evaluate many aspects of burn injury and treatment. He continues to have support from industry to investigate drugs in preclinical trials of drug and equipment safety and efficacy.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
Dr. Traber’s extensive experience with studies on cerebral and cardiac blood flow in the sheep model could be used to study the effects of various regimens of hormone replacement therapy on cerebral blood flow and the cardiovascular system.

DEMONSTRATED RECORD OF MENTORING
As a Professor of Anesthesiology and Director of the Investigational Intensive Care Unit, Dr. Traber has mentored 14 postdoctoral fellows through extensive research projects during the last 5 years.
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RANDALL URBAN, MD
PROFESSOR, DEPARTMENT OF INTERNAL MEDICINE
CHIEF, ENDOCRINOLOGY DIVISION
DIRECTOR, STARK FOUNDATION DIABETES CENTER
CHAIRMAN AD INTERIM, DEPARTMENT OF INTERNAL MEDICINE
rurban@utmb.edu

RESEARCH ACCOMPLISHMENTS
Dr. Urban’s basic research focus is primarily on steroidgenesis in granulosa cells and assessment of steroidogenic enzymes in postmenopausal women and in women with hyperthecosis and polycystic ovarian disease (PCO). Specific research projects include studying the effects of growth factors on steroidogenesis, the physiological and molecular benefits of androgen therapy in older men and women, the effects of thiazolidinediones on reproductive function and growth of cancer cells, and neuroendocrine dysfunction in people after closed-head injury.

FUTURE RESEARCH INTERESTS
Dr. Urban’s major clinical interests are in reproductive endocrinology, diabetes, and thyroid disease.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
Dr. Urban’s research on steroidogenesis and involvement of the steroidogenic enzymes in PCO and hyperthecosis are directly relevant to women’s health issues.

DEMONSTRATED RECORD OF MENTORING
As the former director of the Endocrinology Fellowship Program, Dr. Urban has guided 11 fellows through their postgraduate training in endocrinology. Dr. Urban has trained 9 MDs and 2 PhD postdoctoral fellows.
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CHERYL S. WATSON, PHD
ASSOCIATE DIRECTOR, CENTER FOR INTERDISCIPLINARY RESEARCH ON WOMEN'S HEALTH
PROFESSOR, DEPARTMENT OF HUMAN BIOLOGICAL CHEMISTRY & GENETICS
cswatson@utmb.edu

RESEARCH ACCOMPLISHMENTS
Dr. Cheryl Watson is a professor in the Human Biological Chemistry and Genetics Department at UTMB and has been a faculty member there since 1985. Since that time, she has had continuous independent research funding in the reproductive hormone signaling area. She has participated in many teaching efforts at UTMB in both the graduate and medical schools, including course directorships, curriculum design, and initiation and development of two graduate school course WebCT sites. Her institutional, School of Medicine, and Graduate School for Biomedical Sciences committee contributions have been numerous, including several committee chair positions, and she has served as a faculty senator representing the Graduate School. She is a 2004–2005 Fellow of the Executive Leadership in Academic program. She is also a task force member for developing future directions for the Sealy Center for Environmental Health Sciences including a focus on endocrine disruptor mechanisms of estrogen mimetics. She became Associate Director of the Center for Interdisciplinary Research in Women's Health in 2002, where she represents the interests of basic researchers in this organization.

Nationally, Dr. Watson is a member of the American Society for Cell Biology, the Endocrine Society, and is on the nominating committee of the Women in Endocrinology group. She has chaired and spoken in many national and international scientific symposia, reviewed grant proposals and scientific papers extensively, and recently edited a book summarizing progress to date in her area of expertise. She organized and chaired a Federation of American Societies in Experimental Biology summer conference in her research area, and has since served on the organization committee for this meeting and as the meeting synopsis presenter.

FUTURE RESEARCH INTERESTS
Dr. Watson’s research interests center around the rapid and cell membrane-initiated actions of steroid hormones. Cell membrane receptors for steroid hormones have only recently been recognized as an emerging alternative mechanistic explanation for how steroid hormones work in a wide variety of tissues. Her work focuses on the actions of estrogens through this novel pathway, and how such actions may lead to fresh therapeutic targets and preventive medical approaches. For example, dietary/herbal estrogens may hold safe and effective estrogen replacement opportunities. The effects, risks, and mechanisms involved in environmental estrogen exposures are a major public health concern. More detailed and accurate sex steroid receptor measurements may lead to better diagnosis and tailored treatment strategies for breast cancer patients.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
Of Dr. Watson’s 66 publications, 37 deal directly with the actions of estrogens and progestins via their receptors. Other work has dealt with the mechanisms and receptors for other members of the steroid receptor gene family (for androgens, glucocorticoids, Vitamin D). The experimental systems utilized in her work have often been those representative of female reproductive systems (breast cancer, estrogen receptors in pituitary tumors, and hormonally influenced brain regions). Dr. Watson serves as the Associate Director of the Center for Interdisciplinary Research on Women’s Health, and many of the activities sponsored by her offices are utilized by WRHR Scholars.

DEMONSTRATED RECORD OF MENTORING
Dr. Watson has mentored Master’s and PhD students, postdoctoral fellows, both high school and college summer students, residents, medical students, and junior faculty. She has also established and still operates a cross-department mentoring program for female trainees in research. Additionally, she has participated in campus and nationwide research development programs for minority trainees. Dr. Watson has co-authored 36 publications with trainees.
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ROBERT R. WOLFE, PHD
PROFESSOR, SURGERY, PREVENTIVE MEDICINE & COMMUNITY HEALTH, ANESTHESIOLOGY, AND HUMAN BIOLOGICAL CHEMISTRY & GENETICS
CHIEF, METABOLISM UNIT
SHRINERS BURNS INSTITUTE
rwolfe@utmb.edu

RESEARCH ACCOMPLISHMENTS
Dr. Wolfe is the chief of the metabolism unit at the Shriners’ Hospital for Children-Galveston Burns Hospital and the University of Texas Medical Branch at Galveston. The group consists of approximately 20 investigators, research fellows, and graduate students. The general focus of the research performed by this group is the regulation of metabolism in human subjects. The metabolism unit occupies approximately 4,000 sq ft of the Shriners’ Galveston Burn Hospital and is equipped with all state-of-the-art equipment necessary to perform in vivo stable isotope tracer studies, including seven mass spectrometers and four High-Performance Liquid Chromatography (HPLCs).

FUTURE RESEARCH INTERESTS
Dr. Wolfe’s major focus of interest is in the regulation of protein metabolism, particularly muscle protein. Studies under his direction include elucidation of the factors controlling catabolic response to severe stress, and counter measures to ameliorate the losses in lean body mass. In this light, particular focus is on the relationships between changes in tissue blood flow, amino acid transmembrane transport, protein synthesis, and protein breakdown. Studies are also directed at understanding the interaction between diet and muscle amino acid and protein kinetics, with the applications of these studies ranging from rehabilitation from severe stress to athletic training. Dr. Wolfe is an expert in application of stable isotope tracer methodology to the in vivo study of metabolism, and he has written a comprehensive book on this topic and teaches a course on tracer methodology each year. Also, studies are performed in the UTMB Clinical Research Center, an NIH funded 12-bed facility that offers support in every aspect of performing studies. In addition, a group course is taught through the CRC on clinical research that the trainer will be encouraged to take.

The goal of the training of the young investigator will be a completely self-sufficient, independent investigation capable of obtaining NIH funding. To this end, the trainee will participate in all aspects of the research, including analysis of samples by mass spectrometry and calculation of data. In this regard, Dr. Wolfe and his associates will provide guidance not only in analytical procedures, but also in mathematical modeling and statistical analysis.

RELEVANCE TO THE WRHR CAREER DEVELOPMENT CENTER
Dr. Wolfe is an expert in application of stable isotope tracer technology to the in vivo study of metabolism. These basic technologies can be applied not only to the specific project, directly relevant to women’s health care issues at the time of mentoring, as well as throughout the subsequent career of the young investigator.
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Current WRHR Scholars

Radoslaw Bukowski, MD, PhD, Assistant Professor, Maternal-Fetal Medicine
Entered July 2002; Mentor: Robert Garfield, PhD
rkbukows@utmb.edu

Project: Genome Expression in Uterus in Term and Preterm Labor
After completing residency training in Obstetrics and Gynecology at Eastern Virginia Medical School in 1998, Dr. Bukowski joined the UTMB Department of Obstetrics & Gynecology as an Assistant Professor. In 1999, he became a MFM Fellow at UTMB and completed the fellowship in 2002, after which he became a WRHR Scholar. Dr. Bukowski is currently in his in his third year of WRHR support.

His previous interests have been in cervical ripening, and he has published several papers in this area. He is also interested in fetal growth retardation and has a number of publications on this subject. With the explosion in high throughput screening methods for gene expression, Dr. Bukowski has become interested in changes in gene expression profiles that are associated with complications of pregnancy, and will focus on this as his WRHR research project. In 2003, Dr. Bukowski presented an abstract on regulatory networks of genes in the human uterus in the process of labor at the Society for Gynecologic Investigation meeting. While these studies were in progress, he submitted an R03 application that was scored but not funded. In July 2003, Dr. Bukowski submitted an R01 application titled “Genetic-Environmental Effects on Fetal Growth Potential” in response to RFA HD-03-018 (Research into Mechanism of Fetal Growth Restriction). In June 2004, Dr. Bukowski submitted a R03 application entitled, “Development of Fetal Growth Potential Norms for the USA.” In August 2004, Dr. Bukowski submitted a U01 application entitled, “Genomic/Proteomic Premature Birth Research Clinical Core” in response to HD-04-002 (Genomic and Proteomic Network for Premature Birth Research). Dr. Bukowski is currently a co-investigator on a funded U10 grant (“Scope and Causes of Stillbirth,” PI: George R. Saade, MD).

Hassan M. Harirah, MD, Assistant Professor, Maternal-Fetal Medicine
Entered 2004; Mentors: Bogdan J. Nowicki, MD, PhD, and Chandrasekhar Yallampalli, DVM, PhD
hmharira@utmb.edu

Project: Tissue Remodeling and Apotosis in Preterm Labor

After completing a fellowship at Yale University School of Medicine in 2000, Dr. Harirah joined the UTMB Department of Obstetrics & Gynecology as an Assistant Professor. Dr. Harirah is currently in his first year of WRHR support.

Dr. Harirah’s clinical interests include fetal prenatal diagnosis and therapy, management of high risk pregnancies, thromboembolic disorders of pregnancy, noninvasive biochemical markers for preterm labor, preeclampsia and intra-amniotic infections, and uterine artery Doppler in prediction of preterm labor.

Lubya Levine, MD, MMS, Assistant Professor, Gynecologic Oncology
Entered 2004; Mentors: Mark R. Hellmich, PhD
lylevine@utmb.edu

Project: Endometrial Cancer—Role of Estrogen and Progesterone Receptors in Activation of the Vascular Endothelial Growth Factor and the Intracellular Pathways Involved

Dr. Levine completed her residency in Obstetrics and Gynecology at St. Michael's Medical Center, Newark, New Jersey, and UMDNJ, Newark, New Jersey, in 2000. She completed her fellowship training at the University of Texas Medical Branch, Galveston, Texas, in 2004.

Dr. Levine completed her Master’s in Medical Science at the University of Texas Medical Branch in August 2003. Her research includes, “Endometrial Cancer—Role of Estrogen and Progesterone Receptors in Activation of the Vascular Endothelial Growth Factor and the Intracellular Pathways Involved.” Dr. Levine is also very involved in clinical research conducted by Gynecologic Oncology Group.

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Previous WRHR Scholars

In the past 5 years, our Department has developed considerably from two relatively new fellowship programs in maternal-fetal medicine and gynecologic oncology. These programs have now matured, and we have added a reproductive endocrinology/infertility fellowship. At the completion of his fellowship, one fellow has joined the WRHR program, and several are in position to apply for entrance to the WRHR program in the future. We had a total of five Scholars in the original program. Past Scholars include:

• 3 men, 2 women
• 1 underrepresented minority investigator
• 1 disabled investigator
• A broad distribution of clinical specialties: maternal fetal medicine, gynecologic oncology, reproductive endocrinology infertility, gynecology
• 3 Scholars had virtually no previous research experience
• 2 MD/PhDs
• 1 earned her PhD as a Scholar

Conception Diaz-Arrastia, MD, Assistant Professor, Gynecologic Oncology
Entered January 1999; Mentor: Stephen Tyring, MD, PhD; Mentor: John Papaconstantinou, PhD, 2001.

Dr. Arrastia’s current investigations are yielding excellent results using mass spectroscopy identification techniques to show protein changes in cervical cancer specimens. This work has been presented at national and regional meetings, and forms the basis of a K22 Transitional Career Award for Underrepresented Minorities application.

She was awarded funding to study HPV recurrence in women over 55 years of age by Redes En Acción, a National Institutes of Health—National Cancer Institute/Baylor

College of Medicine Pilot Project. She plans to document the natural history of HPV infection in elderly women, identify the molecular characteristics of elderly women at risk for cervical carcinoma, and establish a proteomic profile for these patients.

Catalin Jurnalov, MD, Assistant Professor, Urogynecology
Entered July 1, 2000, left March 30, 2001; Mentor: Robert Garfield, PhD

Project: Changes in Collagen Metabolism in the Rat Cervix During Pregnancy

Dr. Jurnalov was attracted to the WRHR program at UTMB after completing his fellowship at the Mayo Clinic in 2000. After 9 months in the program, he decided that he was more interested in a full-time clinical practice than in developing a research career. He has remained in the Division of Urogynecology.

Andrea G. Witlin, DO, PhD (2002), Assistant Professor, Maternal-Fetal Medicine, Assistant Professor in Human Biological Chemistry and Genetics
Entered January 1999; Mentor: Chandrasekhar Yallampalli, PhD; Mentor Dr. Alex Kurosky in 2002.

Dr. Witlin was, regrettably, forced by health problems to resign from UTMB and from WRHR Scholarship, effective July 1, 2003. She is a talented and dedicated scientist, and we hope she will eventually be able to return to a productive research role.

Stephen Young, MD, Assistant Professor, Reproductive Endocrinology and Infertility
Entered January 1999, departed June 2000; Mentor: Bogdan Nowicki, MD

In mid 2000, Dr. Young moved on to a position as Assistant Professor, Department of Obstetrics and Gynecology, University of Missouri Hospitals, where he has continued to collaborate with his WRHR Mentor. Although his progress was interrupted by his move to a new institution and delays in completing a new laboratory facility, he and Dr. Nowicki have nonetheless published one paper and submitted a second for publication.

Dr. Young received funding for an R21 grant (Regulation of human TLR3 & TLR9 expression and function), and is serving as a coinvestigator on an R01 awarded to Dr. Kathy Sharpe-Timms. Most recently, Dr. Young began a new line of research made possible by his previous research on innate immune mechanisms with Dr. Nowicki. The new studies are directed toward describing the endometrial expression and function of the Toll-like receptors (TLRs) as key regulators of innate immunity.

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Contact Information for WRHR

For more information please e-mail or call Chandrasekhar Yallampalli, Program Director.

Phone Number: (409) 772-7592
E-mail: chyallam@utmb.edu