First ever 3D anatomical and molecular map of the “little brain” at the heart

We led the development of a unique 3D map of the nervous system in the mammalian heart that combines high-resolution anatomical data and spatially tracked single cell transcriptomics data. This body of work was the first to demonstrate that the neurons in the intrinsic cardiac nervous ­­system express many neuromodulators and downstream signaling pathways.

Achanta et al. A Comprehensive Integrated Anatomical and Molecular Atlas of Rat Intrinsic Cardiac Nervous System. iScience 2020, 23:101140. PMID: 32460006; PMCID: PMC7327996. 

Moss et al. A single cell transcriptomics map of paracrine networks in the intrinsic cardiac nervous system. iScience 2021, 24:102713. PMID: 34337356; PMCID: PMC8324809. 

Leung et al. 3D single cell scale anatomical map of sex-dependent variability of the rat intrinsic cardiac nervous system. iScience 2021, 24:102795. PMID: 34355144 PMCID: PMC8324857. 

Vadigepalli R, Schwaber JS. Mapping the little brain at the heart by an interdisciplinary systems biology team. iScience 2021, 24:102433. PMID: 34113808; PMCID: PMC8169792.

Patented technology for microRNA intervention into essential hypertension

We developed microRNA-based molecular targets to intervene in the development of essential hypertension. We demonstrated that manipulation of two specific microRNAs in the brainstem can normalize the blood pressure setpoint to a healthy level. Importantly, this rescue happens via a coordinated resetting of inflammatory and neuromodulatory pathways such that a single intervention can normalize the blood pressure level for a long time.

Vadigepalli, R., Schwaber, J., & DeCicco, D. Inhibiting MicroDNA to Prevent Development of Essential Hypertension. US. Patent 10,982,214.

Moss et al. Dynamic dysregulation of transcriptomic networks in brainstem autonomic nuclei during hypertension development in the female spontaneously hypertensive rat. Physiological Genomics.2023. PMID: 38145287. 

Single cell transcriptomics and modeling of vagal neurons and circuits driving cardioprotection

We demonstrated that vagal neurons show extensive gene regulatory changes in the setting of physiologically induced protection against cardiac injury. Our computational modeling results are indicating that vagal neuromodulation is coordinated with the intrinsic cardiac nervous system (the “little brain” of the heart) to control cardiovascular physiology.

Gorky et al. Input-output signal processing plasticity of vagal motor neurons in response to cardiac ischemic injury. iScience 2021, 24:102143. PMID: 33665562; PMCID: PMC7898179

Gee et al. Unpacking the multimodal, multi-scale data of the fast and slow lanes of the cardiac vagus through computational modelling. Experimental Physiology 2023. PMID:37120805. 

Gee et al. Closed-loop modeling of central and intrinsic cardiac nervous system circuits underlying cardiovascular control. AIChE Journal 2023, 69:e18033. PMID: 37250861; PMCID: PMC10211393.

Metabolic reprogramming of glucose homeostasis as a hallmark of alcohol-associated hepatitis

We uncovered a surprising component of alcohol-associated hepatitis where liver is reprogrammed to metabolize glucose, which is highly abnormal with severe functional consequences for the rest of the body. Animal experiments are suggesting a sex-dependent mechanism of how alcohol affects liver regenerative capacity. These results change the clinical paradigm of alcohol-associated hepatitis from that of non-functional, diseased liver to that of maladaptive physiology that can be potentially reversed.

Massey et al. Integrated Multiomics Reveals Glucose Use Reprogramming and Identifies a Novel Hexokinase in Alcoholic Hepatitis. Gastroenterology 2021, 160:1725-1740.e2. PMID: 33309778; PMCID: PMC8613537.

Manchel et al. Genome-Scale Metabolic Modeling Reveals Sequential Dysregulation of Glutathione Metabolism in Livers from Patients with Alcoholic Hepatitis. Metabolites. 2022, 12:1157. PMID: 36557195; PMCID: PMC9788589. 

Barnhart et al. Longitudinal ultrasound imaging and network modeling in rats reveal sex-dependent suppression of liver regeneration after resection in alcoholic liver disease. Frontiers in Physiology 2023, 14:1102393. PMID: 36969577; PMCID: PMC10033530. 

Developmental defects tied to uneven, asymmetric capacity for robustness in early development

We demonstrated that early embryo has extensive capacity for robustness to overcome environmental disturbances, which however is asymmetric in that the genotypes that show robustness to perturbations that increase retinoic acid signaling are remarkably poor at counteracting reductions in the same pathway activity, and vice versa. This result suggests an underlying genetic signature of susceptibility or resiliency to environmental insults or dietary challenges in the early development, paving the way for early diagnostics of fetal alcohol spectrum disorders, which are at present impractical to diagnose in preschool age children.

Parihar et al. Retinoic Acid Fluctuation Activates an Uneven, Direction- Dependent Network-Wide Robustness Response in Early Embryogenesis. Frontiers in Cell and Developmental Biology 2021, 9:747969. PMID: 34746144; PMCID: PMC8564372.