BIRCWH Scholars

Niharika Khanna, M.B.B.S. 

Appointment Date: 1/1/2008-12/31/2009

I.  Mentor Team

Edward Sausville, M.D., Ph.D., Professor of Medicine, Associate Director for Clinical Research, University of Maryland Greenebaum Cancer Center

Kevin Cullen, M.D., Director and Professor of Medicine, University of Maryland Greenebaum Cancer Center

Scott Strome, M.D., Professor and Chairman, Department of Otorhinolaryngology, University of Maryland School of Medicine

Sharon Gordon, D.D.S., M.P.H., Ph.D., Associate Professor, Department of Biomedical Sciences, University of Maryland School of Medicine

II.  Proposed Project

Project 1: Efficacy study of Terameprocol in Canine Oral Papillomavirus Model

Specific Aims

Specific Aim 1: To demonstrate the efficacy of Terameprocol in papillomavirus cervical infection using a canine papillomavirus model which mimics genital HPV infection.

Project 2: HPV-related decision making

Specific Aims

Specific Aim 1: To determine facilitators and barriers of acceptance of cervical cancer screening and HPV immunization as viewed by key stakeholders, women ages 18-65, mothers and grandmothers of adolescents by race/ethnicity (African-Americans and non-Hispanic Whites) and to explore knowledge, attitudes, beliefs and risk perception that influence the acceptance of these methods and explore cues to action.

A.  To understand the educational needs of African-American and non-Hispanic White urban women, for primary prevention of cervical cancer, such as the prophylactic HPV vaccine.

B.  To understand the educational needs of African American and non-Hispanic White urban wome, that influence the acceptance of methods for secondary prevention of cervical cancer, such as cervical HPV screening.

Specific Aim 2:  To develop educational programs specifically tailored for key stakeholders, women, mothers and grandmothers, designed to increase awareness and knowledge of cervical cancer disparities, cervical cancer prevention and control, HPV screening and HPV immunization recommendations, and its role in prevention and control of cervical cancer.

Michelle Shardell, Ph.D.

Appointment Date: 1/1/2008-12/31/2009

I.  Mentor Team

Jay Magaziner, Ph.D., Professor and Chair, Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine

Patricia Langenberg, Ph.D., Professor and Vice-Chair, Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine

Marc C. Hochberg, M.D., M.P.H., Professor, Department of Medicine

II.  Proposed Project

Proxy bias in studies of older adults: impact on assessing gender disparities in recovery from hip fracture

Researchers are interested in understanding factors related to recovery from hip fracture.  Identifying these factors is important for tailoring rehabilitation programs.  Facets of recovery may differ between men and women, thus gender may be one important factor for informing rehabilitation programs.  Gender disparities are often assessed using epidemiologic studies that rely on responses to interview questions.  To minimuze missing data and preserve the studies' external validity, proxies (e.g., caregivers or relatives) are often recruited to respond when participants do not respond (e.g., due to refusal or cognitive impairment). However, the proxies may provide incorrect answers to questions about disability, quality of life, depressive symptoms, etc. which can lead to systematic bias that differs between men and women.  Proxies are heavily used in studies of hip fracture patients due to the nature of the injury, thus high levels of differential bias may impede researchers' ability to understand the role of gender post hip fracture.

Specific Aims

Specific Aim 1: Assess whether gender differences in proxy bias of hip-fracture patients' functional and physical health status are partially explained by proxy relationship and living arrangement with the patient. 

Specific Aim 2: Assess whether proxy bias in six-month changes in in post hip fracture functional status is greater in women than in men. 

Specific Aim 3: Extend multiple imputation to accomodate proxy data and scientific background informtation, with and without additional nonresponse.

Peixin Yang, Ph.D.

Appointment Date: 1/1/2008-12/31/2009

I.  Mentor Team

E. Albert Reece, M.D., Ph.D., M.B.A., Vice President for Medical Affairs, University of Maryland, John Z. and Akiko K. Bowers Distinguished Professor and Dean, School of Medicine

Patricia Langenberg, Ph.D., Professor and Vice-Chair, Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine

Istvan Merchenthaler, M.D., Ph.D., Sc.D., Professor, Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine

Jessica Mong, Ph.D., Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine

II.  Proposed Project

Apoptotic Mechanism of Maternal Diabetes-Induced Neural Tube Defects

About 1.85 milliong American women of reproductive age (18-44 years) have diabetes, and the number is increasing due to the obesity epidemic.  Unfortunately, euglycemic control by insulin administration is difficult to achieve as even transient exposure to maternal hyperglycemia causes embryonic malformation.  Thus, maternal diabetes-induced birth defects remain a huge health problem.  Development of accessible, convenient and effective prevention strategies is an urgent task.  To achieve this goal, understanding the mechanism of maternal diabetes-induced malformations is an essential and key step.  Towards this goal, we propose studies that will define the mechanism of diabetic embryopathy at both the cellular and transcriptional levels.

Maternal diabetes remains one of the leading causes of birth defects.  In humans, one of the major malformations induced by maternal diabetes is neural tube defect (NTD).  We use an animal mode in which developing embryos are exposed to maternal hyperglycemia during the critical neurulation period (E8-E11) which causes NTD.  We will specifically focus on the developing neural tubes to delineate the mechanism of maternal diabetes-induced malformations.  We have previously demonstrated that JNK1/2 activation is essential for the induction of embryopathy. In this proposal, we further explore the JNK pathway by identifying the upstream and downstream effectors responsible for JNK1/2 activation in diabetic embryopathy.  Our goal is to identify JNK cascade signaling intermediates responsible for the induction of diabetic embryopathy with the ultimate goal of providing a basis for development of mechanism-based therapeutic agents.

Observation of excessive apoptosis in neural stem cells of malformed neural tubes renders the hypothesis that maternal hyperglycemia-induced apoptosis in neural tube cells results in NTDs.  However, the mechanism of maternal hyperglycemia-induced apoptosis in target tissues remains elusive.  In this proposal, we propose to systematically dissect the mechanism responsible for maternal diabetes-induced NTDs from the signal transduction levels to transcriptional mechanism.  Furthermore, using gene knockout and transgenic animal models, we will discover which apoptotic control proteins mediate maternal diabetes-induced apoptosis.  By unraveling the apoptotic mechanisms leading to diabetic embryopathy, we will provide a mechanistic basis for the use of cutting-edge, mechanism-based therapeutic strategies designed to prevent diabetes-associated birth defects.

Specific Aims

Specific Aim 1: To determine if oxidative stress-dependent ASK1 activation is required for hyperglycemia-induced JNK activation, apoptosis and embryonic malformation.

Specific Aim 2: To determine if Foxo3a is a key downstream medaitor of JNK1/2-dependent apoptosis leading to embryonic malformation.

Specific Aim 3: To determine if Foxo3a is required for hyperglycemia-induced apoptosis and embryo malformation.

Specific Aim 4: We will determine if TRADD function is required for activation of the apoptotic processes involved in maternal hyperglycemia-induced embryopathy.

Jian-Min Zhang, M.D., Ph.D.

Appointment Date: 4/1/2008-3/31/2010

I.  Mentor Team

Margaret McCarthy, Ph.D., Assistant Dean of Graduate Studies and Professor, Departments of Physiology and Psychiatry, University of Maryland School of Medicine

William Regenold, M.D., Associate Professor and Director of Geriatric Psychiatry, Department of Psychiatry, University of Maryland School of Medicine

Leonardo H. Tonelli, Ph.D., Assistant Professor, Department of Psychiatry, University of Maryland School of Medicine

Robert Schwarcz, Ph.D., Professor, Department of Psychiatry, University of Maryland School of Medicine

II.  Proposed Project

Hypothesis: Sex differences in depression in adulthood result in part from the effects of gonadal hormones on the hippocampus during early development.

Specific Aims

Specific Aim 1: To determine whether neonatal androgen exposure has an effect on depression-like behaviors in peri-adolescent rats.

Specific Aim 2: Determine whether neonatal-androgen-induced neurogeneiss and/or gliogenesis in the hippocampus is enduring.