Ph.D.

Assistant Professor

Biochemistry - School of Medicine

Co/post-transcriptional regulation of gene expression by alternative RNA processing is a highly regulated and complex process that exponentially increases the repertoire and dynamic control of gene products. Disrupted RNA processing is implicated in many human diseases, in particular neurological disorders. Alternative RNA processing is regulated by developmental and tissue specific RNA binding proteins (RBPs) which influence core RNA processing machinery. My group will study these regulatory interactions involved in co/post-transcriptional control of neurological development and cell membrane transport/secretion. We will characterize these mechanisms using cutting edge RNA sequencing technology, single-molecule RNA detection, mass-spectroscopy, and CRISPR techniques to address our hypotheses in primary cell lines, patient samples, and animal model systems. This work will advance development of novel clinically relevant biomarkers and therapeutic paradigms for rare genetic and neurological disorders.
   
Choroid plexus mis-splicing and altered CSF composition in myotonic dystrophy type 1.
Myotonic dystrophy type 1 (DM1) is a dominant genetic disease with multisystemic effects. CNS symptoms are among the most debilitating, including behavioral changes, hypersomnia, fatigue, cognitive and memory deficits, early onset MAPT/tau pathology, cerebral atrophy, ventriculomegaly, and intellectual disability. However, the physiological etiology is still unclear, with DM1 associated atrophy in most brain regions and volumetric increases in the amygdala, hippocampus, and ventricles/CSF. Recently, I identified the choroid plexus as one of the most highly affected tissues in DM1 brains with characteristic disease-relevant molecular pathology including CUGexp RNA accumulation and widespread RNA processing alterations. The choroid plexus is composed of a ciliated epithelial cell lining connected by tight junctions to form the blood-CSF barrier, and the ChP-CSF system plays key roles in CNS functions and neural stem cell development. My work has linked disrupted choroid plexus RNA processing to protein content changes in the CSF, revealing that splicing factors play key regulatory roles in extracellular fluid content. My research group will determine the role of the ChP/CSF system in healthy CNS function as well as in pathological conditions such as DM1 with disrupted ChP/CSF regulatory patterns.
   
Decoding transcriptomic regulation of secretory tissues and extracellular fluids.
Extracellular fluids have a high turnover rate (CSF=~6 hours, pericardial=~6 hours, aqueous humor=~2 hours) which is important as they convey nutrients, signaling molecules, and waste to and from the supported tissues. Maintaining tight control and responsiveness of extracellular fluid content by co/post-transcriptional regulation is critical for physiological function. Indeed, diseases with increased aqueous humor production and intraocular pressure can damage the retinal cells and optic nerve leading to vision loss. Although common regulatory mechanisms are expected across secretory tissues, the diverse requirements of extracellular fluid systems predict additional cell-type specific transcriptome regulators as well as developmental stage specific factors. As proof of principal, we have shown that splicing factors regulate genes during development that are essential for maintaining proper secretory function of the ChP/CSF system. DM1 cardiac and ocular dysfunction suggest other secretory/extracellular fluid systems may also be impacted by DM1 pathomechanisms. My research group will decode the co/post-transcriptional regulatory mechanisms that underlie secretory tissue/extracellular fluid physiological functions and develop novel strategies to modulate extracellular fluid content.

Educational background

• Ph.D. Biomedical Sciences, University of Texas Medical Branch
• B.Sc. Agricultural Sciences and Natural Resources, Oklahoma State University