Research Description
Type 2 diabetes (T2D) is a complex disease and highly heterogeneous with respect to clinical features, disease progression, complications, and drug response. The current drug treatment practice is largely based on evidence from clinical trials that do not include all subcategories of T2D patients. Recent studies have identified clusters or subcategories of patients with T2D based on clinical features and underlying pathophysiological process that drives the disease. One such subcategory is T2D patients with severe obesity, insulin resistance, and inflammation of the adipocytes or fat cells. A key barrier to the field is that the molecular basis of what initiates the process of adipocyte inflammation and dysfunction is poorly understood. We have identified a protein kinase, fam20c, which is induced in adipocytes by obesity and seems to be the critical molecular switch that triggers adipocyte inflammation and dysfunction. This proposal seeks to test the hypothesis that precision therapies targeting fam20c in adipocytes will block ongoing adipose inflammation, improve insulin resistance and ameliorate T2D. This will be achieved through 1. Using mouse models of T2D to understand the role adipocyte-derived fam20c in pathogenesis of T2D. 2. To identify key proteins phosphorylated by fam20c that cause adipose tissue inflammation and dysfunction 3. To evaluate precision therapies targeting fam20c for treatment of T2D. Despite numerous advances in the past decade, there are limited to no proven medical therapies that target ongoing adipose inflammation in T2D. This proposal aims to develop new therapies aimed at reversing T2D in patients with inflammatory adipocyte dysfunction.Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?This project aims to identify novel treatments for Type 2 diabetes patients with severe insulin resistance and higher body mass index ratios. These patients have high levels of adipose tissue inflammation and adipocyte dysfunction that worsens disease progression. Currently approved anti-diabetic therapies, at best, control blood glucose and can only treat the disease after it had developed. Moreover, they fail to address the root cause of pathogenesis like inflammatory adipocyte dysfunction, thus making it harder to cure or reverse T2D. We have identified a novel gene called fam20c that regulates adipose inflammation and insulin resistance. Our approach to manipulate fam20c activity and its downstream substrates may ultimately translate into new classes of potent anti-diabetic therapies that can restore metabolic health.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?Over 90% of individuals with type2 diabetes are either overweight or obese. Obese adipose tissue has high levels of inflammation and insulin resistance which drives type 2 diabetes. Despite numerous advances in the past decade, there are limited to no proven medical therapies that target ongoing adipose inflammation in diabetes and hence the disease cannot be cured. Our project is aimed to study a novel target known as fam20c which is induced in adipocytes by obesity and seems to be the critical molecular switch that triggers adipocyte inflammation and dysfunction. We will develop precision therapies targeting fam20c for treatment of type 2 diabetes. Importantly, these therapies will be directed at potentially reversing type 2 diabetes and hence providing a cure to the disease.
Why important for you, personally, to become involved in diabetes research? What role will this award play?My passion in diabetes research stemmed from a personal incident when my grandmother passed away from complications of uncontrolled type 2 diabetes (T2D). Today, my father is suffering from similar complications, and I see him struggling to manage his body weight and blood glucose after taking multiple insulin injections with over 5 prescription medications per day. It is important to note that currently approved antihyperglycemic agents have terribly failed to stop disease progression and do not offer disease reversal or a cure. With passion and ambition, I have decided to dedicate my life to unravel the pathophysiological mechanisms of T2D and find a cure that benefits millions of patients across the globe. This postdoctoral fellowship will serve as a platform to launch my career in diabetes research. Importantly, this funding opportunity will allow me to develop novel T2D treatments targeting novel adipocyte-specific secreted factors. These treatments either alone or in combination with current anti-diabetic medications will potentially cure or reverse type 2 diabetes.
In what direction do you see the future of diabetes research going?Type 2 diabetes (T2D) is defined by a single outcome, hyperglycemia, but is increasingly recognized as a highly heterogeneous disease with varying clinical characteristics, drug response, and risk of complications. The future of diabetes research will be focusing on individualized or precision medicine to target individual-specific pathophysiological mechanisms. Every patient is different and hence more research is required to change the current one-size fits all treatment regimen. Moreover, it is critical to identify causative molecular factors that initiate the disease and to develop safe medications targeting these factors.