Chandrakala Puligilla, Ph.D.
Assistant Professor, Department of Pathology & Laboratory Medicine
A person’s sense of hearing is highly dependent on the cochlear/auditory system of the inner ear. Loss of sensory hair cells, due to prolonged exposure to loud noises, anti-cancer drugs or certain types of antibiotics, is one of the main causes of hearing impairment. Following hair cell loss, neurons which innervate these hair cells and transmit information to the brain are lost. Mammalian inner ear lacks the ability to regenerate or replace these lost cell types and consequently there is progressive and permanent hearing loss within the human ear over time. Therefore, delineating mechanisms that regulate sensory and neuronal cell development is requisite for understanding the basis of hearing loss.
Our laboratory research is focused on understanding critical genetic and molecular mechanisms that that regulate morphogenesis of inner ear, using the mouse as a primary model system. We are especially interested in identifying molecular determinants of sensory hair cell and neuronal development and mechanisms that inner ear utilizes to dictate anatomical position of these cell types and pattern formation and how these processes contribute to perceive sound in the cochlea. Our goal is to understand these cellular processes to provide knowledge required for prevention of hearing loss and for developing strategies to repair hearing defects.
Molecular Determinants of Neuronal & Sensory Lineages
A subset of otocyst-derived progenitor cells delaminates early and gives rise to neuroblasts to form auditory and vestibular ganglion. In addition, some of these progenitor cells become specified as prosensory precursor cells which eventually differentiate into sensory hair cells and support cells. We are currently studying towards identifying molecular signaling pathways that confer prosensory or proneural identity to these cells and will use this information to understand how key pathways interact to direct cell fate decisions that will determine the commitment and differentiation of sensory hair cells and neurons.
Mechanisms that Regulate Cellular Fate & Cellular Alignment
Following the specification of the sensory lineage, the prosensory precursors then given rise to cochlear sensory patches that assume their final fates and differentiate as hair cells or support cells. Subsequently, developing hair cells and support cells become arranged into a highly-organized pattern. The correct cellular patterning is crucial for proper functioning of the cochlea; however it is not clear how the homogenous group of prosensory cells undergo patterning to give rise to distinct cell types in distinct positions within the developing organ of Corti. In addition, mechanisms that regulate this perfect cellular alignment which is essential for biological function are largely unknown. We are currently investigating these processes using a creative combination of cell and molecular biological approaches we are investigating multiple genes that determine cellular fate choices and organization. These studies will improve our understanding of how the temporal and spatial control mechanisms are coordinated to generate this precisely patterned structure or events that interfere with molecular program of development and cause a disruption of its function, thereby providing a framework for future treatment strategies.