Contact Information

Office: 2269C CBRB
Phone: 319-335-2153
Faculty Profile

Brief description of current research:

I am a molecular pharmacologist, and my laboratory aims to understand the role of microRNAs in the gut-heart axis. As a doctoral fellow, I investigated mechanistic associations between metabolic disturbances and prostatic disorders. That research centered on identifying the mechanisms contributing to a high incidence of prostatic disorders in insulin-resistant patients with compensatory hyperinsulinemia. As a postdoctoral fellow, I explored interactions between the intestinal microbiota and microRNAs in vascular disorders. Specifically, I initiated the microbiome-miR research project and identified a unique mode of communication between microbiota and the host, involving remote regulation of miRs with functional implications. I also spearheaded a collaborative project to understand the role of sodium channel trafficking in cardiac arrhythmias. Currently, I am focusing on the role of the microbiota-miR interaction in heart failure. My laboratory identified that the cardiac upregulation of microRNA-204 during hypertrophic stress is a compensatory cardioprotective response. Its effects are mediated by inhibiting the maladaptive stretch signaling of the apelin-receptor. We provide the first evidence that the apelin receptor cellular trafficking regulation by miR-204 changes the signaling outcome of APJ. We also identified that the gamma-peptide nucleic acid-based microRNA inhibition weakens many of the concerns associated with developing microRNA therapeutics (e.g., binding affinity, enzymatic degradation, non-specific interaction with proteins). We think the gamma-peptide nucleic acid will be efficient in microRNA inhibition, safer for long-term use, and suitable for cardiometabolic disorders. Thus, we identify the microRNA targets using cell and small animal-based experiments and test the next generation of microRNA modulators.

4 most influential diabetes/obesity/metabolism publications:

• Gaddam RR, Dhuri K, Kim YR, Jacobs JS, Kumar V, Li Q, Irani K, Bahal R,* and Vikram A.* g-peptide nucleic acid-based miR-122 inhibition rescues vascular endothelial dysfunction in mice fed a high-fat diet. Journal of Medicinal Chemistry. 2022 Feb 24;65(4):3332-3342. [PMID: 35133835, PMCID: PMC8883473]
• Gaddam RR, Kim YR, Jacobs JS, Yoon JY, Li Q, Cai A, Shankaiahgari H, London B, Irani K, and Vikram A*. The microRNA-204-5p inhibits APJ signaling and confers resistance to cardiac hypertrophy and dysfunction. Clinical and Translational Medicine. 2022 Jan;12(1):e693. [PMID: 35060347]
• Gaddam RR, Kim YR, Li Q, Jacobs JS, Gabani M, Mishra A, Promes JA, Imai Y, Irani K, Vikram A.* Genetic deletion of miR-204 improves glycemic control despite obesity in db/db mice. Biochemical and Biophysical Research Communications. 2020 Nov 5;532(2):167-172. [PMID: 32950230]
• Gaddam RR, Jacobsen VP, Kim YR, Gabani M, Jacobs JS, Dhuri K, Kumar S, Kassan M, Li Q, Bahal R, Roghair R, Irani K, Vikram A.* Microbiota-governed microRNA-204 impairs endothelial function and blood pressure decline during inactivity in db/db mice. Scientific Reports. 2020 Jun 22;10(1):10065. [PMID: 32572127]

Quote:

I enjoy my job of investigator as it encompasses dealing with uncertainties and unknowns.