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Zachary Klase

Zachary Klase, PhD

Faculty


Department: Pharmacology & Physiology

Education

  • PhD, Microbiology, Immunology and Tropical Medicine - The George Washington University (2008)
  • BS, Animal Biotechnology - Rutgers University, Cook College (2002)

Awards & Honors

  • USciences: Founder’s Day ‘Faculty Award of Merit’ (2019)
  • USciences: Million Dollar Grantee (2018)
  • Travel Award, Conference on Retroviruses and Opportunistic Infections (2014)
  • Travel Award, Keystone: HIV-1 Pathogenesis (2012)
  • ICAAC Young Investigator Award, American Society for Microbiology (2011)

Memberships / Professional Affiliations

  • American Society of Microbiology
  • International Society of Neurovirology
  • Presbyterian Association for Science, Technology and the Christian Faith
Zachary A. Klase, PhD, is a faculty member in the Department of Pharmacology & Physiology at Drexel University College of Medicine. He comes to Drexel from the University of the Sciences, where he was associate professor and interim assistant chair of the Department of Biological Sciences.

Research Overview

Research Interests

Molecular neuropathogenesis of HIV-1, epigenetic control of transcription and microRNA involvement in viral diseases

Research

Dr. Klase’s research focuses on the study of the human immunodeficiency virus (HIV) the causative agent of acquired immunodeficiency syndrome (AIDS). HIV presents an interesting challenge for two reasons: 1) The virus integrates into the genome of the host cell and can persist for decades, and 2) the viral genome is relatively small, thus requiring the virus to co-opt various cellular processes to be successful.

RUNX Transcription Factors and HIV-1 Latency

Current therapies are capable of blocking viral replication, preventing new infection and decreasing viral load in the blood to undetectable levels. However therapy does not represent a cure, as it does not clear the integrated proviral DNA. HIV infects CD4+ T-cells with a preference for memory T-cells. As memory T-cells are extremely long-lived, an infected memory cell can potentially carry a silent copy of the virus throughout a patient’s lifetime and has the potential to restart an active infection after drug therapy ceases. We call this phenomenon latency. A major portion of the lab’s time is devoted to studying how the RUNX family of transcription factors contributes to latency and how prescription benzodiazepines might be used to alter HIV-1 transcription

HIV-1 and RNA Interference

RNA interference (RNAi) can potentially exert antiviral pressure within a cell. It also represents a very powerful system for controlling gene expression with a cell. As such, it represents a compelling target for a virus to subvert in order to alter host cell gene expression and tune the cellular environment for optimal viral replication. The HIV-1 transcription activator protein Tat has been shown to bind to the RNAi protein Dicer and inhibit the biogenesis of microRNA. The lab studies how Tat may be altering microRNA expression in astrocytes, packaging into exosomes in the CNS, and what role this plays in the neuropathogenesis of HIV-1.

Substance User Disorders and HIV-1

There is, unfortunately, a large overlap between HIV-1 infected individuals and people who abuse drugs. Our main two interests have brought us naturally into this arena. Many of the miRNA that we see dysregulated by the viral Tat protein seem to have a role to play in neuropathogenesis, and we are now studying how these changes are further affected by the presence of opioids. In working with various compounds to address the problem of latency, it has become apparent that many drugs of abuse can be a confounding factor. Long-term exposure to narcotics or street drugs can even change the way our DNA is packaged in the cell. We are actively working to define how this affects the integrated virus and whether this could be part of (or a barrier to) an eventual cure for HIV.

Publications

Recent Publications

"Benzodiazepines Drive Alteration of Chromatin at the Integrated HIV-1 LTR"
Elbezanti W, Lin A, Schirling A, Jackson A, Marshall M, Duyne RV, Maldarelli F, Sardo L, Klase Z
Viruses, 2020;12(2)

"ROR1 regulates chemoresistance in Breast Cancer via modulation of drug efflux pump ABCB1"
Fultang N, Illendula A, Lin J, Pandey MK, Klase Z, Peethambaran B
Scientific Reports, 2020;10(1):1821

"Morphine exposure exacerbates HIV-1 Tat driven changes to neuroinflammatory factors in cultured astrocytes"
Chen K, Phan T, Lin A, Sardo L, Mele AR, Nonnemacher MR, Klase Z
PloS One, 2020;15(3):e0230563

"Strictinin, a novel ROR1-inhibitor, represses triple negative breast cancer survival and migration via modulation of PI3K/AKT/GSK3ss activity"
Fultang N, Illendula A, Chen B, Wu C, Jonnalagadda S, Baird N, Klase Z, Peethambaran B
PloS One, 2019;14(5):e0217789.

"Defining the molecular mechanisms of HIV-1 Tat secretion: PtdIns(4,5)P2 at the epicenter"
Mele AR, Marino J, Chen K, Pirrone V, Janetopoulos C, Wigdahl B, Klase Z, Nonnemacher MR
Traffic, 2018

"A cell surface display fluorescent biosensor for measuring MMP14 activity in real-time"
Braun A, Farber MJ, Klase ZA, Berget PB, Myers KA
Scientific Reports, 2018;8(1):5916

"Myrothamnus flabellifolius selectively targets Triple Negative Breast Cancer in vitro, restoring Tamoxifen Sensitivity through modulation of miRNAs associated with Estrogen Receptors"
Fultang N, Brar J, Mercier I, Klase Z, Peethambaran B
International Journal of Applied Research in Natural Products, 2018;11(1)

"Real-time visualization of chromatin modification in isolated nuclei"
Sardo L, Lin A, Khakhina S, Beckman L, Ricon L, Elbezanti W, Jaison T, Vishwasrao H, Shroff H, Janetopoulos C, Klase ZA
Journal of Cell Science, 2017;130(17):2926-40

"IL-21 and probiotic therapy improve Th17 frequencies, microbial translocation, and microbiome in ARV-treated, SIV-infected macaques"
Ortiz AM, Klase ZA, DiNapoli SR, Vujkovic-Cvijin I, Carmack K, Perkins MR, Calantone N, Vinton CL, Riddick NE, Gallagher J, Klatt NR, McCune JM, Estes JD, Paiardini M, Brenchley JM
Mucosal Immunology, 2016;9(2):458-67

"A CRISPR Approach for Reactivating Latent HIV-1. Molecular Therapy"
Lin A, Klase Z
Journal of the American Society of Gene Therapy, 2016;24(3):416-8

"Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA"
Sampey GC, Saifuddin M, Schwab A, Barclay R, Punya S, Chung MC, Hakami RM, Asad Zadeh M, Lepene B, Klase ZA, El-Hage N, Young M, Iordanskiy S, Kashanchi F
The Journal of Biological Chemistry, 2016;291(3):1251-66

"Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome"
Klase ZA, Khakhina S, Schneider Ade B, Callahan MV, Glasspool-Malone J, Malone R
PLoS Neglected Tropical Diseases, 2016;10(8):e0004877

"The inhibition of microRNAs by HIV-1 Tat suppresses beta catenin activity in astrocytes"
Sardo L, Vakil PR, Elbezanti W, El-Sayed A, Klase Z
Retrovirology, 2016;13:25

"Dysbiotic bacteria translocate in progressive SIV infection"
Klase Z, Ortiz A, Deleage C, Mudd JC, Quinones M, Schwartzman E, Klatt NR, Canary L, Estes JD, Brenchley JM
Mucosal Immunology, 2015;8(5):1009-20

"Destabilization of the gut microbiome marks the end-stage of simian immunodeficiency virus infection in wild chimpanzees"
Barbian HJ, Li Y, Ramirez M, Klase Z, Lipende I, Mjungu D, Moeller AH, Wilson ML, Pusey AE, Lonsdorf EV, Bushman FD, Hahn BH
American Journal of Primatology, 2015

"HIV-1 Nef blocks autophagy in human astrocytes"
Sardo L, Iordanskiy S, Klase Z, Kashanchi F
Cell Cycle, 2015;14(24):3781-2

Presentations

Invited Lectures

“Substances of abuse and HIV-1 cure: Implications for neuropathogenesis”
University of the Sciences, Department of Biological Sciences, January 2020

“Drugs of Abuse and HIV-1 Chromatin Structure”
George Mason University, National Center for Biodefense and Infectious Diseases, September 2018

“Drugs of Abuse and HIV-1 cure: Implications for Neuropathogenesis”
Neuro Infectious Disease Interest Group, NINDS/NIH, April 2017

“Mechanisms of Zika Virus Neuropathogenesis”
Zika Symposa, University of the Sciences and Atheric Pharmaceuticals, August 2016

“HIV-1 Tat inhibition of miRNA”
Drexel University College of Medicine, Institute for Molecular Medicine and Infectious Disease, October 2015


Contact Information


Department of Pharmacology & Physiology
245 N. 15th Street
Mail Stop 488
Philadelphia, PA 19102
Phone: 215.762.4530
Fax: 215.762.2299