Research Activities

Elizabeth O. Beale, MD

Dr. Beale’s research interest is in the role of the gastrointestinal tract in glucose regulation and energy balance. She is the Principal Investigator in studies exploring the mechanisms of the benefit of bariatric surgery in obesity and diabetes, with special areas of interest in bile and incretin effects, and has received grants from the Coulter Foundation for this work. She is also Co-Investigator on Dr. Buchanan’s BetaFat Study.

Thomas A. Buchanan, MD

The BetaGene Study (Genetics of Pancreatic β-cell Failure in Mexican-Americans; NIH R01-DK-061628) has created a cohort of more than 2,000 Mexican-American women, either with gestational diabetes or with normal glucose levels in pregnancy, and their family members. The cohort has been useful in identifying how type 2 diabetes genes contribute to the risk of the disease. The BetaGene cohort is the subject of two NIH research grants on which Buchanan is an investigator. One (R01 DK100302) examines biomarkers that may link genetic variation to phenotypic difference in glucose regulation. The other (R01-DK-105517) examines the impact of genetic risk factors for type 2 diabetes on hepatic glucose and fat metabolism.

The BetaFat Study (Beta Cell Restoration through Fat Mitigation; U01-DK-094430) is a unique collaboration among researchers in diabetes, bariatric surgery and imaging at USC and Kaiser Permanente Southern California. Funding supports a USC-based clinical trial to compare the effects of medical therapy (metformin) to surgical weight loss (gastric banding) on pancreatic beta cell function in adults with pre- or early type 2 diabetes. Dr. Beale serves as a Co-Investigator from the Division. Dr. Namir Katkhouda from the Department of Surgery is Co-Investigator for gastric banding; Dr. Krishna Nayak from the Viterbi School of Engineering is Co-Investigator for MRI studies; and Dr. Anny Xiang of Kaiser Permanente Southern California is co-investigator for data management and analysis. The study extends prior observational and interventional work implicating excess body fat as the primary cause of beta cell failure that leads to type 2 diabetes. If successful, it may lead to new and more aggressive approaches to weight loss early in the course of development of type 2 diabetes.

John D. Carmichael, MD

Dr. Carmichael joined the USC Department of Medicine in 2014 to form the USC Pituitary Center. He holds a joint appointment in the Department of Neurological Surgery. He is Board Certified in internal medicine and endocrinology, diabetes and metabolism, and has completed fellowship training in translational research. He is currently the Principal Investigator for several studies focused on pituitary disease. The LINC Study is a phase 3 multicenter double blind randomized withdrawal study of LCI699, a steroidogenesis inhibitor, following a 24-week, single-arm, open-label dose titration and treatment period to evaluate the safety and efficacy of LCI699 for the treatment of patients with Cushing’s disease. The REAL1 study is a phase 3, randomized, parallel-group, placebocontrolled (double blind) and active-controlled (open) study to evaluate the efficacy and safety of once weekly dosing of NNC0195-0092 with once weekly dosing of placebo and daily dosing of Norditropin® FlexPro® in adults with Growth Hormone Deficiency. The MPOWERED Study is a prospective trial of the use of oral octreotide in the treatment of acromegaly.

Dr. Carmichael is a Co-Investigator for the USC Pituitary Center research registry and database, currently a retrospective database in the process of transforming into a prospective research registry and tumor bank to evaluate genetic, histopathological, radiological and clinical aspects of pituitary tumors. This registry forms the basis for multiple investigations of various pituitary pathologies and already includes data on over 1,400 cases of pituitary tumors operated on at USC. He remains a Co-Investigator on several ongoing studies at Cedars-Sinai Medical Center that he devised and conducted during his tenure there.

Kathleen A. Page, MD

Dr. Page researches how health conditions such as obesity and diabetes are impacted by the functions of the brain. Specifically, she is interested in understanding how the brain regulates appetite and eating behavior, and in identifying early life determinants of obesity, diabetes and cardiovascular disease. An example of these determinates is how exposure to diabetes in utero may lead to an increased risk for obesity and type 2 diabetes.

The American Diabetes Association awarded Dr. Page a prestigious Diabetes Research Accelerator Award in January 2014 as part of the ADA’s bold initiative, “Pathway to Stop Diabetes.” As a result of the award, Dr. Page is researching the impacts of in utero exposure to diabetes on the likelihood of children developing obesity and type 2 diabetes later in life. Through this research, she hopes to better understand how environmental factors impact development of brain pathways that are important in the control of body weight and sugar levels in the blood. Ultimately, the goal is to develop strategies to prevent or counteract certain developmental exposures early in life. Dr. Page is also Principal Investigator on two NIH-funded projects (including an R03 awarded in July 2014) that are aimed at understanding how exposure to maternal gestational diabetes leads to an increased risk for obesity, diabetes and cardiovascular disease in children. Detailed metabolic studies of adipose tissue biology, insulin resistance and insulin secretion in conjunction with neuroimaging studies to examine brain appetite pathways in children are now being conducted. In addition to funding from the NIH, this work is supported by grants from the American Heart Association and Robert E. and May R. Wright Foundation.

Dr. Page’s other research focus is on the role of the brain in the regulation of appetite and feeding behavior in humans. She has received national recognition for this work, including Outstanding Investigator Awards from the Western American Federation for Medical Research, the Endocrine Society and the American Heart Association. Two types of sugar, glucose and fructose, were examined in her studies, and findings to date show that the brain reacts differently to each. Functional magnetic imaging (fMRI) was used to show that lean adults felt more satiated and had decreased activity in the regions of the brain that regulate appetite when they consumed glucose, but not fructose. These findings suggest that while glucose suppresses brain activity in regions that promote the desire to eat, fructose may promote overeating through its inability to effectively suppress the desire to seek out food (Page et al, JAMA 2013; Luo et al, PNAS 2015). Additionally, Dr. Page and team found that obese young adults reported more hunger and a greater desire to eat when they viewed pictures of high-calorie foods such as chocolate cake (Luo et al, Obesity 2013). These images triggered the appetite and reward centers in the brain, and these neural and behavioral responses to high-calorie food stimuli may promote eating. Dr. Page and team are currently conducting additional studies on people’s reactions to dual stimulation of food images and sugar intake. Dr. Page was awarded a prestigious Clinical Scientist Development Award from the Doris Duke Charitable Foundation, in addition to a grant from the American Heart Association to support this work. More recently, she was awarded a $2.7 million R01 grant from the NIH for her related project to determine how high-reward foods, such as sugar, impact the areas of the brain that regulate appetite and food intake in obese, obesity prone and normal-weight young adults.

Anne L. Peters, MD

Dr. Peters is the USC site Principal Investigator for the NIH Look AHEAD Study, a multicenter study designed to assess the benefits of weight loss and exercise on cardiovascular disease risk in patients with type 2 diabetes. The East L.A. cohort offers a unique subset in this national study to show that lifestyle interventions, if done correctly, can succeed in a variety of populations. She is also the USC site Principal Investigator for the Vitamin D and Type 2 Diabetes (D2d) study, a multicenter study designed to assess whether Vitamin D prevents the progression to diabetes in people with pre-diabetes.

Dr. Peters is the Principal Investigator of the Community Diabetes Initiatives (CDI), formally known as the Keck Diabetes Prevention Initiative, a collaborative project with Children’s Hospital Los Angeles designed to work within communities to create sustainable change that can lower rates of childhood and adult obesity and diabetes. Two high-risk populations were chosen for the study: East and South Los Angeles. Community coalitions have been created to help guide efforts to create change. Baseline data was collected and community mapping was performed. Through this project, the CDI has helped bring farmer’s markets to East and South Los Angeles and helped create mentoring programs based on healthy lifestyles in the local schools. Additional projects as part of the CDI include implementing and funding a faith-based diabetes and obesity program in South Los Angeles for children and adults.

Dr. Peters is Principal Investigator of a recently awarded grant for the “STEPP-UP” Trial, funded by the Helmsley Charitable Trust. This is a grant designed to help reduce existing health disparities for lower SES individuals with type 1 diabetes by creating and piloting a program geared for this population. She was a PI in the multicenter study, which showed that continuous glucose monitoring could replace finger-sticks in the management of people with type 1 diabetes. This study led to Medicare approving the coverage of CGM for seniors. Finally, she participated as a PI in the Janssen Phase 2 trial assessing the safety and benefits of Canagliflozin in the treatment of type 1 diabetes. Dr. Peters is the USC PI for Trial-Net, a National Project to screen for and treat people at risk for Type I diabetes.

Carole A. Spencer, PhD

The pioneering work of Dr. Spencer and her clinical colleagues maintains USC’s position on the cutting edge of clinical research in thyroid cancer prognosis and management. Dr. Spencer’s current research focuses on the use of TSH to detect mild (subclinical) thyroid dysfunction in non-pregnant and pregnant patients and the clinical utility of serum thyroglobulin (Tg) and Tg autoantibody (TgAb) measurements in patients with differentiated thyroid carcinomas (DTC). Dr. Spencer’s research has helped establish second-generation (sensitive) Tg immunometric assays as the standard of care for monitoring DTC patients, without the need for recombinant TSH stimulation when TgAb is absent, and the recognition that the trend in TgAb concentrations can serve as a surrogate tumor-marker when TgAb is present.

Hussein Yassine, MD

Dr. Yassine has a strong interest in lipid metabolism and runs the Lipid Clinic at LAC+USC. The Yassine Lab is focused on the role of the omega-3 fatty acid docosahexaenoic acid (DHA) in Alzheimer’s disease, and the mechanisms that regulate its delivery to the brain with an interest in APOE lipidation. He demonstrated that lower levels of DHA associate with greater amyloid deposition in cognitively healthy older adults (JAMA Neurology, 2016), but not in patients with dementia (JAMA Neurology, 2017). In patients with dementia, Dr. Yassine identified an association between APOE4 genotype and reduced levels of cerebrospinal fluid DHA after supplementation (Alzheimer’s Research & Therapy, 2016). Using molecular studies, it was demonstrated that apoE apolipoproteins in cerebrospinal fluid have a decreased capacity to carry lipids by the ABCA-1 transporter, and that its carrying capacity is lower in persons with mild cognitive impairment and Alzheimer’s disease (AD) compared to healthy controls (Journal of the American Heart Association, 2016). In addition, Dr. Yassine is working on strategies to reverse APOE hypolipidation using ABCA-1 agonist therapies with the goal of reducing AD incidence.