Research

Metabolic disorders affect at least one in four adults in the USA and their prevalence increases with age. In North Carolina alone, more than 60% of adults are overweight or obese. Excess body fat, physical inactivity, and poor dietary habits (USDA 2020 dietary guidelines) lead to a gradual onset of insulin resistance that predisposes people of any age to increased risk for severe metabolic, gastrointestinal, and infectious illnesses, including COVID-19. Estimated national spending on direct costs related to these conditions exceeds $90 billion for overweight and obesity, $90 billion for diabetes, and $250 billion for cardiovascular disease.

Studies from our laboratory and others demonstrated that pharmacological interventions or dietary supplementation with plant-derived phytochemicals (botanicals) can ameliorate and, in some cases, slow down the onset and development of these pathologies. While some of the fundamental physiological changes that occur in response to plant-derived bioactive constituents have been described, little is known about the mechanisms and molecular targets by which botanicals modulate energy balance and immune outcomes in our bodies.

We specifically aim to provide a comprehensive assessment of health promoting effects of bioactive constituents from cultivated crops and their wild relatives on in vitro and in vivo measures and mechanism of regulating metabolic, immune, and gastrointestinal system-level responses. The results will be crucial in benefiting the value-added agriculture of North Carolina and the world, while guiding the future preclinical and clinical studies to critically assess the effect of botanicals on modulating metabolism and disease. Novel botanical interventions will also provide a useful and inexpensive adjunct strategy to lifestyle modification. Within this theme, three major initiatives can be used to describe our work:

  • 1) Pharmacogenomics of botanicals and functional foods, and their bioactive constituents of plant and microbial origin, for modulation of metabolism, inflammation, and gut microbiome;

  • 2) Preclinical and early phase human studies in support of novel botanical interventions, including analysis and quantification of hemp cannabinoids (Cannabis sativa, 2018 Farm Bill) in plant tissues and body fluids; and

  • 3) Mobile Discovery program to engage students, organizations, and ethnic communities in biodiscovery from microbial resources, and popularize global health research.

Among the many projects currently being pursued in our lab are the following:

  • Molecular controls linking inflammation to diabetes. We are dissecting the signaling pathways and transcriptional mechanisms that mediate chronic inflammation and associated risk of diabetes. This allows us to define the mode of action of novel bioactive molecules to improve glucose metabolism and glycemic control through analyses of target gene and protein interactions, and preclinical studies in animal models.

  • Structure-activity relationships of plant metabolites and health quality of fruits and vegetables. We determine biological activities of parent plant molecules and their microbial metabolites to identify dietary constituents with maximal potential benefits to public health. Methylated phenolic metabolites, bitter receptor signaling, microbiome, and high yield complete plant proteins are of particular interest. These findings are critical to advance current agricultural, breeding, and genetic approaches to produce better crops.

  • Phenotypical screening in cell culture. We lead discovery of novel bioactives and understanding gene function within the context of energy metabolism in conventional animal and human cell cultures, in vitro human digestion models, 3D cell cultures, and stem cells with potential applications for pharmaceutical, food, and cosmetics industries. This also allows us to develop new genetic tools to directly map human health to plant genomes.

  • Preclinical and early phase human studies in support of safety and efficacy of botanical interventions. We use a variety of animal models and human feasibility studies to study effects of botanicals across different levels of biological organization, including identification and quantification of cannabinoids in plant tissues and body fluids. When necessary, we perform acute toxicity studies to obtain single-dose LD50, MTD (few days), subacute repeated dose toxicity (14 days), and subchronic toxicity to establish NOEL (90 days).

  • Discovery and scientific validation of traditional ethnic medicines. We are dedicated to incorporate traditional medicinal knowledge into modern healthcare and ensure it meets the safety and efficacy standards. We also explore microbes of diverse habitats for discovery of novel metabolites with application to human health (Mobile Discovery).

Facilities

Our facilities consist of 3 functional units that offer a wide range of services to the research community, including cutting edge technologies, high end instrumentation, technical support, and education. Our lab personnel are highly trained experts in their field who provide technical expertise, consultation, and training. We are fully committed to enhancing and expanding the collaborative capabilities of research at NC State University, North Carolina Research Campus, and throughout the world.



  • Metabolic biology suite. The main lab is equipped with ABI Gene Amp 9700 PCR and 7500 Fast Real-Time PCR thermal cyclers, BioTek Synergy H1 microplate reader (absorbance, fluorescence, and luminescence), XF-24 Seahorse Extracellular Flux Analyzer, BD Accuri C6 Flow Cytometer, Sorvall RC6 Plus and Legend T Plus centrifuges, and multiple instruments for routine nucleic acid and protein analysis, including Western blot and ELISA.


  • Cell culture and phenotyping suite. The Biosafety Level 2 lab is equipped with a laminar-flow hood, CO2 incubator, Bellco Roll-In Incubator, Microscope Imaging System, Orflo Moxi automated cell counter, refrigerators (4 °C), freezers (-20 °C), ulta-low freezers (-80 °C), and a liquid nitrogen freezer (-190 °C) for long-term storage and cryopreservation.


  • Analytical chemistry and microbiology suite. This lab handles isolation and characterization of bacterial and fungal cultures from environmental and microbiome samples. It is equipped for extraction, quantification, and synthesis of natural products from fermentation and plant material to support discovery of novel pharmacological leads including a laminar-flow hood, isotemp incubators, New Brunswick Scientific Innova43 and I2500 shakers, Labconco Freezone18 bulk tray freeze drier, Buchi R210 rotavapor with Multivapor P12 parallel evaporator, Shimadzu Prominence LC-2030C HPLC, bench centrifuges, scales, hotplates, vortexes, and pH meters.


  • Additional resources. We also have unrestricted at-cost access to the AAALAC-accredited Center for Laboratory Animal Sciences (CLAS), full analytical capabilities of the DHMRI Institute, and the shared core facilities of the UNC Chapel Hill.