Terry Hinds, Jr, PhD

Advanced Technology in the Lab

The Hinds Lab team leads cutting-edge science with the most advanced technology for studying signaling pathways: the PamGene PamStation. The Hinds Lab has specialized expertise in using this state-of-the-art instrument to measure hundreds of kinase signaling activities in a single sample, which requires much time for their lab’s extensive bioinformatic analysis. This technology is likely the future of personalized medicine, making the University of Kentucky one of the first sites globally to use this advanced instrumentation. The Hinds Lab purchased and established the equipment with startup funds and support from the Vice President of Research (VPR). UK is only the fourth site in the U.S. to have this technology. The Hinds lab is highly innovative, built for novel omic approaches using advanced technology, and welcomes collaboration.

Landmark discoveries from the lab include 1) the discovery of the murine nuclear receptor gene for glucocorticoid receptor β (GRβ) (PMID: 20660300) and the creation of all of the tools for studying this GR isoform; 2) developed the only human GRβ antagonist (Patent WO 2017155929 A1); 3) discovered that bilirubin is a hormone that activates nuclear receptors; 4) generated a bilirubin-derived molecule called Thin Molecules and patented their use for obesity and diabetes treatments (Patent Number WO 2017151469 A1); and 5) developed bilirubin nanoparticles as a therapeutic for the treatment of obesity, diabetes, and cardiovascular diseases (Patent Number WO-2020-176289 A1). Our latest work, which cannot be disclosed because of patentability, is leading-edge work where we have discovered new hormones that cause obesity-associated comorbidities.  

Hinds Lab Clinical Trial 

The Hinds Lab with Dr. Kyle Flack's lab has a Clinical Trial at the University of Kentucky where we study obese humans and whether increases in plasma bilirubin and exercise help them lose weight faster. https://clinicaltrials.gov/ct2/show/NCT04717726?term=NCT04717726&draw=2…

Research Interests

My lab’s research is on how nutrients from the diet and hormones regulate metabolic dysfunction in obesity and diabetes. We have discovered new hormones that control the metabolic process. From these discoveries, we have generated compounds that we have patented as potential future therapeutics. Our studies open new fronts for understanding metabolic dysfunction and possible treatments.

The lab's focus is to understand the molecular mechanisms in the liver and adipose tissues that regulate fat accumulation and insulin resistance that leads to type II diabetes. We are primarily focused on nuclear receptors, heme oxygenase, and drug targeting. When a red blood cell undergoes its life span and breaks open, it releases heme that carries the oxygen. The heme oxygenase system (heme oxygenase-1, biliverdin reductase, and UGT1A1 glucuronyl enzymes) breaks the heme down to biliverdin and then bilirubin. Increasing bilirubin in the obese reduces body weight and improves insulin signaling. However, mechanisms explaining how bilirubin controls obesity and insulin resistance were unknown for nearly two decades. We discovered and established the concept that bilirubin is a metabolic hormone by binding to the nuclear receptor PPARalpha. Current investigations on how bilirubin controls metabolic dysfunction are ongoing. We have developed and patented bilirubin nanoparticles and other bilirubin-derived molecules as potential therapeutics for metabolic disease. We are working to understand the role of the proteins that regulate bilirubin's turnover, such as the enzyme that produces it, biliverdin reductase (BVR), and the glucuronyl enzyme that clears it from the body, UGT1A1. Studies have been focused on targeting these enzymes in diet-induced fatty liver disease and insulin-resistant diabetes. Together, our studies provide new avenues for drug targeting with therapeutic interventions that are translational for patient studies.

New studies are investigating an IRB-approved small clinical trial where we are using dietary supplements to increase plasma bilirubin in obese patients with and without exercise to determine if this improves weight-loss outcomes. Our studies may reveal new fronts for understanding how metabolic dysfunction and lower bilirubin affect our body's peripheral responses to fat accumulation, leading to insulin-resistant diabetes.

Areas Of Expertise

Drug design, signaling, nuclear receptors, kinases, obesity and diabetes, metabolic pathways, drug metabolism (P450 and glucuronidation enzymes), heme oxygenase and bilirubin pathway, oxidative stress, cancer-inducing pathways, and development of cancer (bladder and prostate mostly, but also others).