The Department of Internal Medicine has a thriving and rapidly expanding research portfolio that spans the entire spectrum of biomedical research from genes and molecules to translation of discoveries in the community. The researchers within various divisions are actively engaged in cutting-edge pursuits of discovery that promise to shape the future of patient care. With the inception of a Cardiovascular Research Institute and a new Research Office, the department has witnessed unsurpassed enthusiasm and support for research during the past year.
The research in our department is supported by grant awards from the National Institutes of Health, other national agencies, clinical trials, and philanthropy. We are particularly proud of our success in this area. Indeed, Internal Medicine’s reputation for outstanding research was reflected in the amount of federal and private support we received. We saw an impressive 33 percent increase in the number of new grants in 2010, a 51 percent increase in total grant funding in the last 10 years, and a remarkable 136 percent increase in new grant dollars awarded to the Internal Medicine Department in 2010.
Curiosity, imagination, motivation, perseverance, and expertise. These are some of the attributes that our researchers share to perform the extraordinary work that they have done over the past year. We are extremely proud of all of our investigators, and feature three who represent the wonderful group that we are fortunate to have. Their work truly has the potential to transform lives through research.
The number of people affected by kidney disease is staggering. According to the National Kidney Foundation, an estimated 26 million Americans are living with kidney disease, and millions more are at increased risk for the development of this disorder.
Dr. Jason Stubbs recently received a National Institutes of Health K08 Award to explore the interrelationships of mineral metabolism pathways in kidney disease. Dr. Stubbs will use molecular methodology to define the role of aberrant phosphate and vitamin D metabolism as contributors to the co-morbidities associated with progressive kidney disease.
More specifically, his research will focus on fibroblast growth factor 23 (FGF23), a novel hormone produced by bone that has been found to regulate phosphorus and vitamin D levels in the body. Circulating levels of FGF23 are extremely elevated in patients with chronic kidney disease, and this increase has been independently associated with increased morbidity and mortality in this population. The discovery of this hormone has challenged the traditional hypothesis regarding the origins of mineral metabolism abnormalities in patients with chronic kidney disease. Dr. Stubbs and others have postulated that the early production of FGF23 from bone is an inciting event leading to subsequent mineral metabolism abnormalities in patients with chronic kidney disease. Dr. Stubbs plans to use a mouse model of progressive kidney disease to elucidate the complex interaction between mineral metabolism pathways in relation to FGF23, and to identify the specific contributions of these pathways to the vascular and bone pathologies that are common in this setting.
Dr. Steven Weinman is leading NIH-funded projects to determine how hepatitis C virus (HCV) infection interacts with alcohol and other environmental stresses to produce liver injury, cirrhosis, and hepatocellular carcinoma.
Previous work from his group demonstrated that the viral core protein regulates mitochondrial calcium uptake, resulting in direct increases of mitochondrial superoxide production; alterations of cell death pathways; and oxidative modification of DNA, proteins, and lipids. In collaboration with Dr. Prashant Pandya, his laboratory has also recently shown that HCV-infected patients have a worse outcome than non-infected patients when they develop alcoholic hepatitis.
Dr. Weinman’s current research is leading the way in understanding how HCV alters normal liver protective responses to alcohol and interferes with pathways that regulate antioxidant function, autophagy, and cell proliferation. This work is aimed at developing new clinical approaches to reduce liver injury produced by HCV and alcohol.
The JAK-STAT axis plays a critical role in signaling initiated by various growth factors as related to cell survival and apoptosis. Over the past decade, Dr. Yu-Ting Xuan’s work has identified a role of this pathway in protection of heart muscle against ischemic injury, a phenomenon termed “ischemic preconditioning.” With extensive experience in cellular and molecular biology, Dr. Xuan is a leader in our quest to utilize this information in protecting the heart during heart attacks.
Currently, Dr. Yu-Ting Xuan’s NIH-funded research is focused on understanding the complex signaling pathways involved in the activation of transcription factors leading to the upregulation of cardioprotective proteins during myocardial ischemia/reperfusion injury and ischemic preconditioning. In related projects, Dr. Xuan’s team is also working on improving the survival of bone-marrow-derived adult stem cells after transplantation into the heart. If successful, results from these projects are likely to benefit thousands of patients with coronary artery disease who experience heart attacks.
We want to thank all of our researchers for their contributions to the advancement of medicine, and for continuing to keep the Department of Internal Medicine in the spotlight for innovative and groundbreaking medical discoveries.