BBTAD Trainees 2005-06
- Joseph R. Kurian, Ph.D.
- Michael J. Peterson, M.D., Ph.D.
- Elizabeth A. Shirtcliff, Ph.D.
Joseph R. Kurian, Ph.D.
My graduate research focused on the metabolism of 4-aminobiphenyl (a component of cigarette smoke) and sulfonamide antimicrobials, which form toxic metabolites (hydroxylamines) in vivo that are associated with carcinogenesis and severe idiosyncratic drug toxicities with risk of death. I found that two proteins (NADH cytochrome b5 reductase (b5R) and cytochrome b5), which are generally regarded as "helper" enzymes, were together sufficient and necessary for detoxification of hydroxylamines in humans. in vitro examinations indicated wide individual variability in liver hydroxylamine metabolism and genetic variability in cytochrome b5 was associated with altered hydroxylamine metabolism. I concluded that individual variability in cytochrome b5 or b5R contribute to hydroxylamine reduction capacity and further predicted this variability would be indicative of adverse outcome. I was also involved in the development of a clinical test that measures cytochrome b5 activity in blood samples. This test is intended to serve as a clinical marker for individual hydroxylamine detoxification capacity and may provide a means to modify dosing protocols to avoid idiosyncratic drug toxicity development.
While my graduate training focused entirely on biological approaches, my postdoctoral training will augment my ability to develop behavioral approaches to answering questions related to typical and atypical development. My research will again investigate individual differences, but the focus will extend beyond heritable traits. I am particularly interested in studying epigenetic phenomena, such as gene promoter methylation, which is modifiable through early experience in a rat model and stable through life. Recent reports indicate that maternal pup licking is associated with estrogen receptor-α (ERα) gene promoter methylation in pups and eventual licking behavior by the pups towards their own litters (Champagne, 2006). ERα expression is associated with behaviorally linked neuropeptides including oxytocin (OT) and vasopressin (AVP) as well as their respective receptors, which are associated with affiliative behavior and social bonding. Altered expression of ERα as a result of early experience associated methylation events would be predicted to modify the release or expression of these neuropeptides or receptors. My proposed research as a BBTAD fellow will study the role of maternal care on ERα, OT and AVP expression and eventual performance in behavioral tests including juvenile play behavior and social preference. These studies will encompass each of the cells of the BBTAD matrix, focusing on the interface of behavior and biology modified by typical and atypical rearing environments. There will be particular focus on developing behavioral paradigms that mimic typical and atypical rearing environments and measure affiliative and social bonding behavior in typically and atypically reared animals.
Michael J. Peterson, M.D., Ph.D.
I completed my undergraduate degree in Integrative Biology at the University of California, Berkeley. While at Cal, I became interested in developmental biology and had the opportunity to work in laboratories there, and as a summer research fellow at the Worcester Foundataion for Experimental Biology. After completing my degree, I had the opportunity to work at the University of California, San Francisco investigating health and developmental biology. After this, I moved to Wisconsin, and entered the Medical Scientist Training Program at the Medical College of Wisconsin. I completed my Ph.D. in Biochemistry investigating gene regulation in normal and disrupted blood cell differentiation. When returning to the clinics, I found a good fit for my interests and personality in Psychiatry, and became intrigued with the research opportunities in the neurosciences. After completing my M.D., I entered the psychiatry residency program at the University of Wisconsin, Madison, intent on an academic career blending clinical practice and research. I graduated from the residency program in 2005, and continued the following year in the department as the HealthEmotions Research Fellow.
During the coming year, I will work toward establishing independence as an investigator through the BBTAD Program. Dr. Ruth Benca will be my primary mentor, with a focus on understanding developmental changes in sleep, both in healthy subjects and those with psychiatric illnesses. Sleep disruptions are one of the most common symptoms of psychiatric illnesses, particularly mood disorders. Additionally, the onset of depression is common during adolescence and early adulthood. Both behavioral and biological aspects of sleep change during this period as well, and sleep disruption may share a common biology with the onset of mood disorders. We will be studying the behavioral changes in sleep during both typical and atypical development from adolescence to adulthood. Working with Dr. Guilio Tononi's lab, we will apply hd-EEG polysomnography and TMS-EEG to further elucidate the biological basis of behavioral changes in sleep.
Elizabeth A. Shirtcliff, Ph.D.
I am a behavioral endocrinologist who seeks to understand developmental factors that lead to atypical adolescent development. My doctoral studies investigated stress responsive salivary hormones, such as cortisol. I was then awarded a post-doctoral fellowship on the Emotion Training Grant at UW-Madison in order to try to understand how emotional experiences influence stress responses. During this post-doctoral period, Dr. Chris Coe sparked my interest in developmental research. We began to discuss ways to understand how early experiences might shape the maturation of the stress system. The result of these conversations will culminate on the Biological and Behavioral Approaches to Typical and Atypical Development (BBTAD) training grant.
To become an independent developmental scientist, I will broaden my biological expertise to include training in typical and atypical approaches to development. I plan to (1) Gain insights into typical and atypical development by looking at youth with a broad range of early experiences; (2) Apply developmental models to stress regulation; and (3) Learn about adolescence. Mentorship from Dr. Seth Pollak will focus on designing empirical studies to test experiential canalization as a mechanism for stress regulation. We will examine stress regulation in adolescents who have been internationally adopted from institutional settings in order to isolate atypical experiences in early development. Adolescents who have experienced chronic stress exposure (i.e., child maltreatment) will also be studied in order to clarify whether early development is a critical epoch. Finally, I will study whether hypothesized alterations in setpoints for stress regulation are malleable by examining adolescents who have presumably canalized along a deleterious pathway and are currently entering a mental health institution. Stress regulation will then be measured before and after youth benefit from behavioral intervention. These three populations of atypically developing adolescents will help me determine whether biological and behavioral profiles are established in early development or across the entire lifespan, and whether stress regulation profiles can be altered through environmental change in adolescents.