1. People

Ajit Vikram, PhD

Assistant Professor of Internal Medicine-Cardiovascular Medicine

Current Positions

  • Assistant Professor of Internal Medicine-Cardiovascular Medicine

Education

  • MS, Pharmacology, National Institute of Pharmaceutical Education and Research (India), Mohali, India
  • PhD, Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (India), Mohali, India

Center, Program and Institute Affiliations

Research Interests

  • 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 per se and its regulation by miR-204, leading to a change in 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). Based on the robust preliminary data, generated in collaboration with Dr. Raman Bahal from the University of Iowa, we think that the gamma-peptide nucleic acid will be efficient in microRNA inhibition, safer for long-term use, and suitable for cardiometabolic disorders. In summary, the focus is always on utilizing the interdiciplenery expertise to tackle the real challenges in cardiovascular diseases.

Selected 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] *Corresponding author.
  • 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] *Corresponding author.
  • Momin MY, Gaddam RR, Kravitz M, Gupta A, and Vikram A.* The Challenges and Opportunities in the Development of MicroRNA Therapeutics: A Multidisciplinary Viewpoint. Cells. 2021. 9;10(11):3097. *Corresponding author. [PMID: 34831320].
  • 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] *Corresponding author.
  • 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] *Corresponding author.
  • Vikram, A., Lewarchik, C. M., Yoon, J., Naqvi, A., Kumar, S., Morgan, G. M., Jacobs, J. S., Li, Q., Kim, Y., Kassan, M., Liu, J., Gabani, M., Kumar, A., Mehdi, H., Zhu, X., Guan, X., Kutschke, W., Zhang, X., Boudreau, R. L., Dai, S., Matasic, D. S., Jung, S., Margulies, K. B., kumar, V., Bachschmid, M. M., London, B. & Irani, K. (2017). SIRTUIN1 REGULATES CARDIAC ELECTRICAL ACTIVITY BY DEACETYLATING THE CARDIAC SODIUM CHANNEL. NATURE MEDICINE 23 361-367. DOI: 10.1038/nm.4284.
  • Vikram, A., Kim, Y., Kumar, S., Li, Q., Kassan, M., Jacobs, J. S. & Irani, K. (2017). THE MICROBIOME REMOTELY PROMOTES ENDOTHELIAL DYSFUNCTION THROUGH VASCULAR MICRORNA-204-MEDIATED DOWNREGULATION OF SIRTUIN1. NATURE COMMUNICATIONS. (7) 12565. DOI: 10.1038/ncomms12565.
  • Tikoo, K., Vikram, A., Shrivastava, S., Jena, G., Shah, H. & Chhabra, R. (2017). PARENTAL HIGH-FAT DIET PROMOTES INFLAMMATORY AND SENESCENCE-RELATED CHANGES IN PROSTATE. OXID MED CELL LONGEV (2017:4962950). DOI: 10.1155/2017/4962950. PMID: 28261375. PMCID: PMC5316447.
  • Vikram, A., Jena, G. & Ramarao, P. (2010). PIOGLITAZONE ATTENUATES PROSTATIC ENLARGEMENT IN DIET-INDUCED INSULIN-RESISTANT RATS BY ALTERING LIPID DISTRIBUTION AND HYPERINSULINAEMIA. BRITISH JOURNAL OF PHARMACOLOGY 161 (8) 1708-1721. DOI: 10.1111/j.1476-5381.2010.00994.x.
  • Vikram A, Jena GB, Ramarao P, Increased cell proliferation and contractility of the prostate gland in insulin-resistant rats: Linking hyperinsulinemia with prostatic hyperplasia. Prostate, 1 (2010) 79-89. [PMID: 19790233].

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