Research Description
Obesity has emerged as a significant global health problem, contributing to an increase in glucose levels in the body. However, the underlying causes of obesity and effective treatment strategies remain elusive. Dr. Sadaf Farooqi, a renowned scientist from the University of Cambridge in the UK, made a remarkable discovery while studying two boys suffering from severe obesity. Dr. Farooqi identified a gene called Transient Receptor Potential Channel 5 (TRPC5) that had undergone permanent changes in the genetic makeup of the boys' cells. TRPC5 is a gene primarily found in the brain and plays a crucial role in regulating body weight. Unraveling the reasons behind the connection between the TRPC5 gene mutations and obesity in humans has proven challenging. Therefore, animal models, particularly mice were used to shed light on this relationship. The mice the humanized Trpc5 gene mutation increased body weight and consumed more high-caloric foods. These findings raise the initial question: why does the mutation in the Trpc5 gene result in obesity? The most important thing is to explore potential treatment for individuals with the TRPC5 gene mutations. A hypothesis was raised that obesity caused by the TRPC5 gene mutations could potentially be treated using medications, such as melanocortin and oxytocin. The proposed studies will uncover the underlying mechanisms and develop precision medicine approaches for individuals who do not have the normal TRPC5 gene.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?My research projects mainly focus on the gene mutation and obesity development, which can result in Type 2 diabetes. Specifically, this project will focus on the TRPC5 gene that we firstly identified recently, which is the most strongly associated X-linked gene for human body mass index (BMI). I found that loss of function TRPC5 mutations can cause human obesity, and this gene should be included in the genetic diagnostic panel for obesity. The open questions are how TRPC5 deficiency causes obesity and how we can treat these individuals with TRPC5 deficiency. My objectives are to 1) reveal the genetic basis for human obesity and 2) unravel the underlying mechanisms for these genetic obesity syndromes, with a hope that my results can enhance clinical practices to better diagnose genetic obesity and to guide precision medicine that target the pathophysiology underlying the disease.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?My project will identify how rare TRPC5 gene mutation affects the development of obesity that may lead to type 2 diabetes. I have found that TRPC5 mutant can lead to obesity as well as hyperphagia. In addition, studies of rare penetrant variants can provide valuable mechanistic insights of direct relevance to human physiology and pathophysiology which can be challenging to identify in common, more heterogeneous forms of obesity.
Why important for you, personally, to become involved in diabetes research? What role will this award play?Obesity is a serious global health problem due to its increasing prevalence and comorbidities, which can lead to Type 2 diabetes. However, a major question in the field still remains unsolved: what cause human obesity? Recent studies revealed genetic and epigenetic basis for variations in human BMI, and strikingly the majority of BMI-associated genetic variants affect genes that are enriched in the nervous system. Thus, the dysfunctions of the brain have been implicated in susceptibility of obesity development in humans. I am working on neuroscience and hope find new solutions or target for obesity treatment. This award provides me with dedicated research time to delve into my area of interest and facilitates my participation in diabetes-related conferences.
In what direction do you see the future of diabetes research going?I believe in the near future; a clearer understanding of the gene mutation and obesity development will be discovered. Hopefully, we can identify novel mechanisms for human body weight regulation and to look for novel targets for precision medicine for obesity and Type2 diabetes.