The Hamad Laboratory
Research InterestsOur research interest is crystalized into three main areas:
Type-1 diabetes. This is an autoimmune disease that strikes early in life due to the destruction of insulin-producing beta cells by autoreactive T cells. Our focus is on understanding how the Fas death pathway regulates the disease and how extracted information can be used to protect high risk individuals and those with new-onset disease. To reach this goal, we study the disease in the non-obese diabetic (NOD) mouse model and directly in humans using peripheral blood from patients and organs from deceased donors. NOD mice bearing loss-of-function mutation in Fas or FasL are completely protected from the disease, indicating that irregularities in this pathway drive disease development. We go to humans to find out what mechanisms that work in NOD mice are most relevant to the human disease so that they could be understood and eventually targeted to interrupt disease development. Currently, we are pursuing a subpopulation of B cells that is characterized by high expression level of FasL a cell death-inducing molecule to determine why it is expanded in T1D patients and whether blunting their trajectory can inhibit disease development. We are currently analyze underlying mechanism, antigen specificity and defects in the Fas pathway that trigger the onset of insulitis and progression into overt disease.
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Type 2 diabetes and Obesity. Obesity is a chronic disease with serious health consequences. The increase in the rate of obesity largely explains the epidemic increase in the prevalence of type 2 diabetes. Weight loss of 5 to 10% has been shown to reduce complications related to obesity and improve quality of life; however, weight loss is difficult to maintain with lifestyle intervention alone. Our lab is studying the role of heparan sulfate proteoglycans (HSPG) in regulating body fat and glucose clearance. Our data point to a major role for heparan sulfate proteoglycans (HSPGs) in regulating body fat and glucose tolerance. NTKT cells using knockout mice and biological intervention.
Double negative αβT cells. This population of alpha/beta T cells is found in small numbers in lymphoid tissues but significantly higher numbers in non-lymphoid tissues. Homeostasis of this population is regulating by the Fas pathway as inactivation of the Fas pathway leads to their predominance in lymphoid tissues and what is referred to as autoimmune lymphoproliferative disease (ALPS). We have also identified the kidney as a major site for DN T cells. Our studies suggest a critical role for these cells in protecting kidneys from Ischemia reperfusion injury (IRI). Our current focus is understanding their origin and physiological functions.
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