Subha Arthur, PhD
Associate Professor 
arthursu@marshall.edu

Research Interest 

My research interests broadly focus on understanding intestinal ion and nutrient transport processes, with emphasis on their regulation in pathophysiological states such as inflammatory bowel disease and obesity. My current work aims to decipher the functional and molecular mechanisms underlying increased intestinal bile acid absorption in obesity, with the ultimate goal of identifying potential therapeutic targets to alleviate obesity and its associated dyslipidemia which are the primary drivers of several chronic metabolic disorders such as cardiovascular disease and diabetes, the major contributors of premature mortality in this country. Using two etiologically distinct rat models of obesity—genetic and diet-induced—my lab has demonstrated that intestinal bile acid absorption, mediated by the apical sodium-dependent bile acid co-transporter (ASBT) in villus cells, is significantly elevated in obesity. Notably, high-fat diet exposure upregulated ASBT expression prior to the onset and progression of dyslipidemia, suggesting that increased intestinal bile acid absorption via ASBT may be the initiating event in obesity-related lipid abnormalities. Further investigations revealed that ASBT is upregulated not only at the cellular level, but also along the crypt-villus and caudal-oral axes of the small intestine. This multilayered upregulation of ASBT in obesity likely amplifies net bile acid absorption and contributes to enhanced fat absorption, implicating dysregulated ASBT as a central player in the pathogenesis of obesity. Ongoing research is focused on elucidating the intracellular mechanisms that regulate ASBT in proximal and distal small intestine to identify a novel, intestine-specific target to reverse ASBT-mediated bile acid hyperabsorption, thereby mitigating obesity-associated dyslipidemia and other metabolic disorders.

The approaches applied in my laboratory include molecular, cellular, and integrative methodologies. These methods include west blot, real-time PCR, mass spectrum, microRNA sequencing, nanosight tracking analysis (NTA), flow cytometry, etc. Animal surgery methods (MCAO, telemetric probe, osmotic minipump, microinjection) are also used in my research. The animal models used in my research include a spontaneous hemorrhagic stroke model induced in the rennin/angiotensinogen double transgenic (R+A+) hypertensive mice, collagenase-induced focal hemorrhagic stroke model, middle cerebral artery occlusion (MCAO)-induced ischemic stroke, the db/db and STZ-induced diabetic mouse models. Additionally, I use clinical samples from translational studies of diabetes and stroke patients through collaboration with clinicians.