Dr. Yelamanchili's Laboratory

RESEARCH INTERESTS

RESEARCH STATEMENT

The overarching goal of my independent research program is to understand the role of regulatory molecules such as genes, proteins, and microRNAs in the pathogenesis of neurological disorders and drug addiction.

Methamphetamine (Meth) and related amphetamine compounds, which are potent psychostimulants, are among the most commonly used illicit drugs. With more than 35 million users worldwide, Meth abuse poses significant health and economic threats globally. Acute and chronic doses of Meth have been shown to produce long-term damage in many brain regions. However, the mechanisms underlying Meth neurotoxicity are still not known. An important and emerging player is extracellular vesicles (EVs) and their role in chronic Meth abuse.

Extracellular vesicles (EVs) have been garnering increasing interest for their role in several neurological disorders and understanding their role in the brain during drug abuse is just beginning to emerge. EVs can release their cargo into target cells and trigger downstream signaling pathways. Our studies have revealed that EV associated microRNA (miRNA) cargo can be responsible for neuronal injury. However, EV miRNA cargo and their involvement in Meth associated neurotoxicity are not well understood thus warranting further studies in this direction. We are particularly interested in understanding the effect of such EV-carried miRNAs on neurons. We have successfully shown to use various model systems including human biospecimens, rhesus macaques in addition to rodent models and in vitro work to study the pathogenesis in the brain.

Present work in my laboratory focuses on investigating the role of extracellular vesicles and their microRNA cargo in chronic methamphetamine abuse and during HIV infection.

Apart from the projects highlighted above, my laboratory is also interested to study the long-term effects of prescription drugs (pain medications and anesthetics) in the brain. To study these effects we are developing both animal as well as in vitro models in the laboratory.

LAB PERSONNEL

Subhash Chand, Ph.D.
Post-Doctoral Research Associate
Hanuma Kumar Karnati, Ph.D.
Post-Doctoral Research Associate

Katherine Odegaard
Graduate Research Assistant

Farah Shahjin
Graduate Research Assistant
Austin Gowen
Research Technologist I
   


Positions are currently open for Ph.D. students and/or postdoctoral fellows. Applicants should submit a current CV, contact information for three references, and a statement of the experimental area they would like to pursue to: Sowmya Yelamanchili, Ph.D.

 

LAB TECHNIQUES

LAB NEWS

FUNDING

Role of extracellular vesicles in methamphetamine-induced neurotoxicity
Study Period: Sept. 2016 - June 2021
PI: Yelamanchili
Source: NIH/NIDA- R01 DA042379
This project aims to understand the role of extracellular vesicles (EVs) in chronic Methamphetamine (Meth) abuse. EVs can actively serve as mediators of communication between various cells including within the CNS. Our preliminary studies indicate that Meth can indeed increase EV biogenesis and release. The overarching goal of this proposal is to examine the role of EVs in the damaging effects of Meth on the CNS, specifically in a setting of chronic Meth exposure. During the course of this study, we will investigate several key questions in the field including molecular and functional changes in neurons that are specifically driven by EVs during Meth abuse.

Chronic HIV Infection and Aging in NeuroAIDS (CHAIN) Center
MPI: S. Buch and H. Fox; Core Co-Investigator: Yelamanchili
Source: 3P30MH062261
This is a Center grant to provide Administrative and Core Support for scientists investigating NeuroAIDS.

NIH/NIDA R21DA046855 
Role of extracellular vesicles in methamphetamine and HIV induced neurotoxicity
PI: Yelamanchili and Kashanchi
Source:NIH/NIDA R21DA046855 
Extracellular vesicles have been garnering increasing interest for their role in several neurological disorders including drugs of abuse. The cause of rapid disease progression of HIV infection in CNS with methamphetamine synergy abuse is unclear; however, our studies indicate a role of extracellular vesicles. Our studies proposed here are designed to uncover their role in the progression of disease in CNS in a setting of HIV and methamphetamine abuse.

Extracellular vesicles, meth relapse and sex differences
PI: Pendyala
Source: NIH/NIDA R01DA046852-01
The overarching goal of this proposal is to examine the role of EVs in the damaging effects of meth between the sexes using drug-triggered reinstatement (relapse) of extinguished intravenous meth self-administration in rats.

Extracellular vesicles as the vehicles for promoting liver injury induced by HIV and alcohol
PI: Poluektova
Source: NIH/NIAAA R01AA027189-01A1
The application proposes to test the hypothesis that ethanol metabolism amplifies HIV-triggered communication between hepatocytes and macrophages via large extracellular bodies, thereby promoting liver inflammation and fibrosis. The proposal addresses a highly significant HIV co-morbidity as liver disease is the second-leading cause of mortality in HIV-infected patients.

Defining microRNA-induced inflammation during chlamydia infection
PI: Yeruva
Source: NIH/NIAID R21AI146521

PUBLICATIONS

  1. Moore D, Meays BM, Madduri LV, Guda C, Niu M, Pendyala G, Fox HS and Yelamanchili SV#. Downregulation of an evolutionary young miR-1290 in an iPSC derived neural stem cell model of autism spectrum disorder. (Stem cell International, In press, 2019)
  2. Shahjin F, Chand S and Yelamanchili SV#. Extracellular vesicles as therapeutic carriers. Invited review, JNIP (In press, 2019).
  3. Hu G, Yelamanchili S, Kashanchi F, Haughey N, Bond VC, Witwer KW, Pulliam L, Buch S. Proceedings of the 2017 ISEV symposium on "HIV, NeuroHIV, drug abuse, & EVs". J Neurovirol. 2017 Dec;23(6):935-940. PMID: 29147885
  4. Harrison EB, Emanuel K, Lamberty BG, Morsey BM, Li M, Kelso ML, Yelamanchili SV, Fox HS. Induction of miR-155 after Brain Injury Promotes Type 1 Interferon and has a Neuroprotective Effect. Front Mol Neurosci. 2017 Jul 28;10:228. PMID: 28804446 
  5. Harrison EB, Hochfelder CG, Lamberty BG, Meays BM, Morsey BM, Kelso ML, Fox HS, Yelamanchili SV. Traumatic brain injury increases levels of miR-21 in extracellular vesicles: implications for neuroinflammation. FEBS Open Bio. 2016 Jun 14;6(8):835-46. doi: 10.1002/2211-5463.12092. PubMed PMID: 27516962; PubMed Central PMCID: PMC4971839.
  6. Yelamanchili SV, Lamberty BG, Rennard DA, Morsey BM, Hochfelder CG, Meays BM, Levy E, Fox HS. MiR-21 in Extracellular Vesicles Leads to Neurotoxicity via TLR7 Signaling in SIV Neurological Disease. PLoS Pathog. 2015 Jul 8;11(7):e1005032. doi: 10.1371/journal.ppat.1005032. Erratum in: PLoS Pathog. 2015 Sep;11(9):e1005131. PubMed PMID: 26154133; PubMed Central PMCID: PMC4496044.
  7. Basma H, Gunji Y, Iwasawa S, Nelson A, Farid M, Ikari J, Liu X, Wang X, Michalski J, Smith L, Iqbal J, El Behery R, West W, Yelamanchili S, Rennard D, Holz O, Mueller KC, Magnussen H, Rabe K, Castaldi PJ, Rennard SI. Reprogramming of COPD lung fibroblasts through formation of induced pluripotent stem cells. Am J Physiol Lung Cell Mol Physiol. 2014 Mar 15;306(6):L552-65. doi: 10.1152/ajplung.00255.2013. PubMed PMID: 24487392; PubMed Central PMCID: PMC3949084.
  8. Yelamanchili SV, Morsey B, Harrison EB, Rennard DA, Emanuel K, Thapa I, Bastola DR, Fox HS. The evolutionary young miR-1290 favors mitotic exit and differentiation of human neural progenitors through altering the cell cycle proteins. Cell Death Dis. 2014 Jan 9;5:e982. doi: 10.1038/cddis.2013.498. PubMed PMID: 24407235; PubMed Central PMCID: PMC4040694
  9. Chaudhuri AD, Yelamanchili SV, Marcondes MC and Fox HS (2013). Upregulation of MicroRNA-142 in Simian Immunodeficiency Virus Encephalitis leads to Repression of Sirtuin1.FASEB J. 2013 Jun 10. PMID 23752207
  10. Chaudhuri AD, Yelamanchili SV and Fox HS (2013). Combined Fluorescent in situ Hybridization for detection of microRNAs and Immunofluorescent Labeling for Cell-Type Markers. Frontiers in Cell. Neurosci. Sep 23;7:160 PMID 24065888
  11. Chaudhuri AD, Yelamanchili SV and Fox HS (2013). MicroRNA-142 Reduces Monoamine Oxidase A Expression and Activity in Neuronal Cells by Downregulating SIRT1. Plos One, 8(11):e79579. PMID 24244526
  12. Hu G, Yao H, Chaudhuri AD, Duan M, Yelamanchili SV, Wen H, Cheney PD, Fox HS, Buch S (2012). Exosome-mediated shuttling of microRNA-29 regulates HIV Tat and morphine-mediated neuronal dysfunction.  Cell Death and Disease. Aug 30; 3:e381. PMID 22932723
  13. Yelamanchili SV, Chaudhuri AD A, Flynn C, Fox HS (2011). Upregulation of Cathepsin D in the caudate nucleus of primates with experimental parkinsonism. Molecular Neurodegeneration, Jul 21; 6:52 PMID 21777416
  14. Yelamanchili SV, Datta-Chaudhari A, Chen L, Xiong H and Fox HS. MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease. Cell Death Dis., 2010, 1 (9) e77. PMID 21170291
  15. Yelamanchili SV and Fox HS. Defining Larger Roles for "Tiny" RNA Molecules: Role of miRNAs in Neurodegeneration Research. J. Neuroimmune Pharmacol., 2010, 5:63-69. PMID 19757077
  16. Darna M, Schmutz I, Richter K, Yelamanchili SV, Pendyala G, Holtje M, Albrecht U, Ahnert-Hilger G. (2009) Time-of-day dependent sorting of vesicular glutamate transporter to the plasma membrane. J Biol Chem, 284(7):4300-07
  17. Darna M, Schmutz I, Richter K, Yelamanchili SV, Pendyala G, Holtje M, Albrecht U, Ahnert-Hilger G (2009). Time-of-day dependent sorting of vesicular glutamate transporter to the plasma membrane. J Biological Chemistry 284(7): 4300-7
  18. Yelamanchili SV, Pendyala G, Brunk I, Darna M, Albrecht U, Ahnert-Hilger G (2006) “Differential sorting of the Vesicular Glutamate Transporter 1 into a defined vesicular pool is regulated by light signaling involving the clock gene Period2”, Journal of Biological Chemistry 281, 15671-15679

Additional publications in PubMed.

COLLABORATORS

Howard S. Fox, M.D., Ph.D., Department of Pharmacology and Experimental Neuroscience, UNMC
Rick Bevins, Ph.D., Department of Psychology, University of Nebraska, Lincoln
Gurudutt Pendyala, Ph.D., Department of Anesthesiology, UNMC
Siddappa Byrareddy, Ph.D., Department of Pharmacology and Experimental Neuroscience, UNMC
Anna Dunaevsky, Ph.D., Developmental Neuroscience, Munroe-Meyer Institute (MMI), UNMC
Shilpa Buch, Ph.D., Department of Pharmacology, UNMC
Fatah Kashanchi, Ph.D.
, George Mason University, Virginia
Laxmi Yeruva, Ph.D., Arkansas Children's Hospital Research Institute
Hakho Lee, Ph.D., Harvard University
Philip Schwartz, Ph.D., Childrens Hospital at Orange County (CHOC), Orange County, California