Education

Postdoctoral Fellow
McGovern Medical School, The University of Texas Health Science Center at Houston – 2018
Ph.D.
The Medical University of South Carolina, 2015

Areas of Interest

Research Interests

Stress-induced cAMP signaling in cardiovascular tissue and vascular inflammation

Research Information

Stress-induced cAMP signaling in cardiovascular tissue and vascular inflammation

Cardiovascular disease (CVD) affects more patients globally than all forms of cancer and chronic lower respiratory disease combined. Alarmingly, these illnesses are known to contribute to approximately one-third of annual deaths worldwide. Thus, further elucidation of the etiology and molecular mechanism driving CVD pathophysiology to support the development of novel treatments is critical in combating this urgent unmet medical need.

During the onset of CVD, disruption of physiological conditions triggers stress responses such as cAMP signaling within the heart and vessels to attempt to restore normality. However, extended stimulation of stress observed in these chronic afflictions can ultimately become detrimental and further augment disease progression. Our laboratory explores the exchange proteins directly activated by cAMP (EPACs) which are one of the internal effectors functioning downstream of cAMP stress responses in the cardiovascular system. When diseases manifest, EPAC levels are altered suggesting a potential involvement of the cAMP effector in several pathogenic processes.

Currently, I am interested in exploring the signaling mechanisms of EPAC in a multitude of obstructive vascular conditions. Thus, a major focus of my research is linked to interrogating pathologically relevant mechanisms associated with EPAC from a global perspective that can be characterized molecularly and subsequently targeted with small molecule inhibitors to improve cardiovascular conditions in intact animals. Demonstrating the success of this approach to therapeutic target development, our lab and others demonstrated EPAC involvement in neointima hyperplasia, where we show EPAC specific inhibitors directly recapitulating the protective phenotype attained with genetic knockout animals. Furthermore, with my background in molecular pharmacology, G-protein / cAMP signalosomes, and inflammatory immunology, I have an avid interest in discovering how distinct functional roles of EPACs in endothelial, smooth muscle, and immunological cells ultimately converge to produce more complex pathogenic manifestations observed in human patients.

In order to facilitate these efforts, parallel approaches of genetic ablation and pharmacological modulation are applied in intact animal models of vascular disorders, thus defining conceivable benefits of EPAC attenuation in the prevention and/or treatment of CVD states. Furthermore, characterization of these models with non-invasive disease monitoring, tissue and cellular phenotyping, and successive biochemical analysis are currently underway to delineate the intricate and precise EPAC-signaling systems present under these stressful vascular environments. I am optimistic that distinct EPAC-mediated pathways driving the observed phenotypes can be adequately explored with our current molecular tools and models, and I also plan to extend these findings to other relevant disease models including inflammatory disease, diabetes, and cancer in the upcoming years. Taken together, I consider the multifaceted strategies currently being implemented to be crucial for the understanding and advancement of EPACs as a therapeutic focus in patients suffering from CVD.

Publications

Publication Information

REFERENCES

  • Robichaux III WG and Cheng X. (2018). Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology and Therapeutics Development. Physiological Reviews. Apr 1; 98 (2): 919-1053. PMID: 29537337.
  • Robichaux III WG, Branham-O’Connor M, Hwang IL, Vural A, Kehrl, JH, and Blumer, JB. (2017).  Regulation of Chemokine Signal Integration by Activator of G-protein Signaling 4 (AGS4). Journal of Pharmacology and Experimental Therapeutics. Mar; 360 (3): 424-433. PMID: 28062526.
  • Wang H, Robichaux III WG, Wang Z, Cai M, Du G, Chen J, Mei FC, Cheng X. (2016).  Inhibition of Epac1 Suppresses Mitochondrial Fission and Reduces Neointima Formation Induced by Vascular Injury. Scientific Reports. Nov 10; 6: 36552. PMID: 27830723.
  • Hu Y, Robichaux III WG, Mei FC, Kim ER, Wang H, Tong Q, Jin J, Xu M, Chen J, and Cheng X. (2016).  Role of Exchange Protein Directly Activated by Cyclic AMP Isoform 1 in Energy Homeostasis: Regulation of Leptin Expression and Secretion in White Adipose Tissue. Molecular and Cellular Biology. Sep 12; 36 (19): 2440-50. PMID: 27381457.
    • Further Article Acknowledgement: Molecular and Cellular Biology Spotlight Section Article: Oct 2016.
  • Robichaux III WG, Oner SS, Lanier SM and Blumer JB. (2015).  Direct Coupling of a Seven- Transmembrane-Span Receptor to a Gαi G-Protein Regulatory Motif Complex. Molecular Pharmacology. Aug; 88 (2): 231-7. PMID: 25972449.
    • Further Article Acknowledgment: Molecular Pharmacology Highlighted Article: Jul 28, 2015.
  • Branham-O’Connor M, Robichaux III WG, Zhang XK, Cho H, Kehrl JH, Lanier SM, Blumer JB. (2014). Defective Chemokine Signal Integration in Leukocytes lacking Activator of G Protein Signaling 3 (AGS3). J Biol Chem. Apr 11; 289 (15): 10738-47. PMID: 24573680.