Kathleen E. Corey, MD, MPH is a member of the faculty of the Gastrointestinal Division of Massachusetts General Hospital (MGH) and an instructor in medicine at Harvard Medical School (HMS). Dr. Corey has a background in patient oriented research, gastroenterology and hepatology. Her research has focused on the interaction between lipid metabolism and chronic liver disease, specifically hepatitis C and non-alcoholic fatty liver disease (NAFLD). Her work in these areas has resulted in 8 first author publications including the identification of a two lipid biomarkers, oxidized low density lipoproteins (OxLDL) and non-high density lipoprotein cholesterol for NAFLD. In addition, her recent study assessing protective factors for the development of NAFLD, she found that obstructive sleep apnea (OSA) was one of the strongest predictors of normal liver histology in patients with obesity, suggesting that OSA may play a role in NAFLD development. Both OSA and NAFLD are important public health conditions. NAFLD affects 30% of Americans and can lead to cirrhosis and hepatocellular carcinoma. More than 12 million Americans are estimated to suffer from OSA which worsens metabolic disease and increases the risk of cardiovascular disease and sudden death. The study of these conditions and their interactions will lead to new treatment options and improved public heath outcomes. Using knowledge gained from these studies, Dr. Corey's proposal will focus on testing three hypotheses;1) OSA is associated with an increased prevalence of NAFLD, 2) The interaction between OSA and NAFLD is mediated by lipid peroxidation as measured by OxLDL and 3) Treatment of OSA in patients with NAFLD will improvement in steatosis. While animal studies have found a strong relationship between chronic intermittent hypoxia, the experimental mimic of OSA, and NAFLD, human studies have been limited by methodologic issues leading to inconclusive results. To complete this proposal Dr. Corey will require additional training in study design, statistical analysis and obstructive sleep apnea mechanics. Dr. Corey will benefit from the guidance of her two co-mentors, Dr. Raymond Chung, an established basic and clinical investigator in hepatology and Dr. Atul Malhotra, an established physician-scientist in the study of OSA. Both Drs. Chung and Malhotra have established track records in the mentoring of clinical investigators and both hold NIH K24 awards. Dr. Corey will also receive mentoring from Dr. Steven Grinspoon, an established investigator in metabolic studies and K24 recipient and Dr. Shiva Gautam, an experience biostatistician and mentor. She will receive formal didactic training in study design, advanced biostatistics, and predictive modeling from the Master in Medical Science Program at Harvard Medical School. She will also receive training in OSA pathophysiology through courses at Harvard- Massachusetts Institute of Technology Health Sciences and Technology, lead by her co-mentor, Dr. Malhotra. With this additional education and guidance, as well as the supportive environment provided by the MGH, Dr. Corey will be well poised to complete this proposal and develop into an independent clinical investigator.

Public Health Relevance

Non-alcoholic fatty liver disease (NAFLD) affects nearly one third of Americans. NAFLD can lead to the development of cirrhosis, liver cancer and the need for a liver transplant. The purpose of this study is to assess the impact of obstructive sleep apnea on the development of NAFLD and determine if treating sleep apnea improves NAFLD.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mentored Patient-Oriented Research Career Development Award (K23)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Podskalny, Judith M,
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Massachusetts General Hospital
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Soti, Subada; Corey, Kathleen E; Lake, Jordan E et al. (2018) NAFLD and HIV: Do Sex, Race, and Ethnicity Explain HIV-Related Risk? Curr HIV/AIDS Rep 15:212-222
Simon, Tracey G; Corey, Kathleen E; Cannon, Christopher P et al. (2018) The nonalcoholic fatty liver disease (NAFLD) fibrosis score, cardiovascular risk stratification and a strategy for secondary prevention with ezetimibe. Int J Cardiol 270:245-252
Simon, Tracey G; Trejo, Maria Esther Perez; McClelland, Robyn et al. (2018) Circulating Interleukin-6 is a biomarker for coronary atherosclerosis in nonalcoholic fatty liver disease: Results from the Multi-Ethnic Study of Atherosclerosis. Int J Cardiol 259:198-204
Simon, Tracey G; King, Lindsay Y; Chong, Dawn Q et al. (2018) Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: Results from two prospective cohort studies. Hepatology 67:1797-1806
Alves-Bezerra, Michele; Li, Yingxia; Acuña, Mariana et al. (2018) Thioesterase Superfamily Member 2 Promotes Hepatic VLDL Secretion by Channeling Fatty Acids into Triglyceride Biosynthesis. Hepatology :
Simon, Tracey G; Bamira, Daniel G; Chung, Raymond T et al. (2017) Nonalcoholic Steatohepatitis is Associated with Cardiac Remodeling and Dysfunction. Obesity (Silver Spring) 25:1313-1316
Klebanoff, Matthew J; Corey, Kathleen E; Chhatwal, Jagpreet et al. (2017) Bariatric surgery for nonalcoholic steatohepatitis: A clinical and cost-effectiveness analysis. Hepatology 65:1156-1164
Kimberly, W Taylor; O'Sullivan, John F; Nath, Anjali K et al. (2017) Metabolite profiling identifies anandamide as a biomarker of nonalcoholic steatohepatitis. JCI Insight 2:
Dichtel, Laura E; Corey, Kathleen E; Misdraji, Joseph et al. (2017) The Association Between IGF-1 Levels and the Histologic Severity of Nonalcoholic Fatty Liver Disease. Clin Transl Gastroenterol 8:e217
Kartoun, Uri; Corey, Kathleen E; Simon, Tracey G et al. (2017) The MELD-Plus: A generalizable prediction risk score in cirrhosis. PLoS One 12:e0186301

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