Prakash Kharel, PhD

Professional Background

I am an Assistant Professor in the Department of Biochemistry and Molecular Biology at the University of Kansas Medical Center. My laboratory aims to elucidate the role of RNA secondary structures—particularly non-canonical structures known as G-quadruplexes (G4s)—in cellular biology and disease pathogenesis. RNA G4s are critical regulators of various stages of the RNA life cycle, including transcription, processing, transport, translation, and stability. Although thousands of potential RNA G4 (rG4)-forming sequences exist in the human transcriptome, only a subset of these sequences adopt G4 structures at any given time. To investigate the functional and disease-related implications of specific rG4s, we employ a multidisciplinary approach that integrates biochemical, biophysical, cellular, genetic, and next-generation sequencing techniques. Our current research focuses on uncovering the role of G4 structures in several disease models, including Facioscapulohumeral Muscular Dystrophy (FSHD), Parkinson’s Disease (PD), and Amyotrophic Lateral Sclerosis (ALS).

• BSc, Chemistry, Birendra Multiple Campus, Nepal
• MS, Chemistry, Tribhuvan University, Nepal
• PhD, Biochemistry, Kent State University, Kent, OH
• Post Doctoral Fellowship, RNA biology and cellular stress response mechanisms, Brigham and Women's Hospital/ Harvard Medical School, Boston, MA

Research

Overview

There are thousands of putative G4-forming sequences in the human genome and transcriptome. Particularly in RNA, only a fraction of potential rG4s actually fold into rG4s. Importantly, different stress environments, such as oxidative stress, starvation, and temperature shock, drive rG4 folding in human cells. Furthermore, several rG4 binding proteins are involved in regulating the folding-unfolding dynamics of cellular rG4s. Potential rG4-forming sequences are present in several disease-relevant RNAs, including oncogenes and genes relevant to several repeat-associated disorders. My lab aims to identify which G-rich sequences are truly folded into rG4s under pathogenic circumstances, and what the binding partners are that help such phenomena.
Current priorities of my lab are:
(1) Biology of nuclear rG4ome
(2) DUX4 Metabolism in FacioScapuloHumeral Muscular Dystrophy (FSHD)
(3) Molecular Mechanisms of C9ORF72 G4C2 Repeat-induced toxicity in ALS/FTD